Feasibility of Total Neoadjuvant Treatment With HYPErthermia in Patients With High-risk Extremity and Trunk Soft Tissue Sarcoma (TNT-HYPE). A Multicenter, Single Arm, Open Label, Phase II Trial

Soft tissue sarcomas (STSs) are rare cancers with a 5-year survival rate of 60%, and there is no standard treatment for high-risk extremity and trunk STSs (eSTS). A phase III trial suggests that adding moderate regional hyperthermia (HT) to anthracycline-based chemotherapy, followed by surgery and radiotherapy (RT), can improve 10-year overall survival by 10%. This trial aims to optimize treatment by combining the most effective regimens from chemotherapy, HT, RT, and surgery, and will evaluate the feasibility of this new total neoadjuvant treatment (TNT) approach.

Start Date15 May 2025

Sponsor / Collaborator

Swiss Group for Clinical Cancer Research

NCT06820957

/ Not yet recruitingPhase 2/3IIT

Randomized Phase 2/3 Trial of Vincristine-Irinotecan-Regorafenib in Combination With Vincristine-Doxorubicin-Cyclophosphamide (VDC) and Ifosfamide-Etoposide (IE) in Patients With Newly Diagnosed Metastatic Ewing Sarcoma

This phase II/III trial compares the effect of vincristine, irinotecan, and regorafenib (VIrR) in combination with vincristine, doxorubicin, cyclophosphamide (VDC), ifosfamide and etoposide (IE) to usual treatment with VDC/IE for the treatment of newly diagnosed Ewing sarcoma or other round cell sarcomas that have spread from where they first started (primary site) to other places in the body (metastatic). Vincristine is in a class of medications called vinca alkaloids. It works by stopping tumor cells from growing and dividing and may kill them. Irinotecan is in a class of antineoplastic medications called topoisomerase I inhibitors. It blocks a certain enzyme needed for cell division and deoxyribonucleic acid (DNA) repair and may kill tumor cells. Regorafenib, a type of kinase inhibitor and a type of antiangiogenesis agent, blocks certain proteins, which may help keep tumor cells from growing. It may also prevent the growth of new blood vessels that tumors need to grow. Doxorubicin is in a class of medications called anthracyclines. Doxorubicin damages the cell's DNA and may kill tumor cells. It also blocks a certain enzyme needed for cell division and DNA repair. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill tumor cells. It may also lower the body's immune response. Ifosfamide, a type of alkylating agent and a type of antimetabolite, attaches to DNA in cells and may kill tumor cells. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill tumor cells. Giving VIrR/VDC/IE may be more effective than usual treatment with VDC/IE in treating patients with newly diagnosed metastatic Ewing sarcoma or other round cell sarcomas.

Start Date15 Apr 2025

Sponsor / Collaborator

The Children's Oncology Group Foundation, Inc.

NCT06647953

/ Not yet recruitingPhase 3IIT

Prospective Treatment of Types I, II and III Pleuropulmonary Blastoma (PPB)

This phase III trial tests how well surgery plus chemotherapy compared to surgery alone works in treating patients with type I pleuropulmonary blastoma (PPB), and tests how well surgery plus standard chemotherapy with the addition of topotecan works compared to surgery plus standard chemotherapy alone in treating patients with type II and III PPB.
Historically, most children with type I PPB had surgery and approximately 40% of children with type I PPB received chemotherapy following their surgery, usually for 22-42 weeks. There has not been a consistent standard for which children with type I PPB receive chemotherapy after surgery. For patients whose tumor has been removed completely with surgery, observation without chemotherapy may work as well as giving chemotherapy after surgery in preventing a return of the PPB tumor.
The standard chemotherapy for patients with types II or III PPB in the United States is four cycles of IVADo (ifosfamide, vincristine, dactinomycin, and doxorubicin) followed by 8 cycles of IVA (ifosfamide, vincristine and dactinomycin). Ifosfamide is in a class of medications called alkylating agents. It works by slowing or stopping the growth of tumor cells in the body. Vincristine is in a class of medications called vinca alkaloids. It works by stopping tumor cells from growing and dividing and may kill them. Dactinomycin is a type of antibiotic that is only used in cancer chemotherapy (antineoplastic antibiotic). It works by damaging the cell's deoxyribonucleic acid (DNA) and may kill tumor cells. Doxorubicin is in a class of medications called anthracyclines. Doxorubicin damages the cell's DNA and may kill tumor cells. It also blocks a certain enzyme needed for cell division and DNA repair. Topotecan is in a class of medications called topoisomerase I inhibitors. It works by interfering with tumor cell DNA which kills them. Giving topotecan in addition to standard IVADo and IVA chemotherapy regimens may shrink the cancer as well as or better than the standard therapy or could decrease the chance the tumor spreads while causing fewer side effects.

Start Date17 Mar 2025

Sponsor / Collaborator

The Children's Oncology Group Foundation, Inc.

100 Clinical Results associated with Ifosamide

100 Translational Medicine associated with Ifosamide

100 Patents (Medical) associated with Ifosamide

9,797

Literatures (Medical) associated with Ifosamide

01 Apr 2025·Journal of Oncology Pharmacy Practice

Cytotoxic surface contamination in hospitals: Current practices, challenges and perspectives

Review

Author: Darnis, Sophie ; Gilles, Laurence ; Tokatian, Sophie ; Basset, Mathurine ; Guitton, Jérôme ; Simonin, Claire ; Favier, Bertrand ; Chabaud, Sylvie

ObjectiveDespite significant advances in cancer treatment with targeted therapies and immunotherapies, cytotoxic chemotherapies are still extensively used. Potential cytotoxic contamination in preparing and administrating cytotoxics is still a major source of concern. Besides advanced protections including biological safety cabinets, work surface contamination needs to be continuously controlled to ensure that handling procedures and cleaning were appropriate. Contamination monitoring needs to be standardized.Data SourcesThe study searched Pubmed/Medline and Embase with"hazardous drug”, “cytotoxic drug”, “surface contamination”, “environmental contamination”, “wipe sample”, “pharmacy”, “care unit”, and selected studies reporting contamination results in work environment for pharmacy technicians and nurses, from 1 January 2017 to 31 December 2022.Data Summary The 29 studies totalized 16,196 samples and 189,571 assays. Contamination results showed 39.8% sample positivity, and 8.2% assay positivity. Multicentric studies gathering at least 500 samples or up to 800 samples would limit heterogeneity in sample positivity. In addition, monitoring of an appropriate tracer selection including at least the 7 tracers with the highest contamination frequencies (cyclophosphamide, gemcitabine, fluorouracile, ifosfamide, platinum derivatives, paclitaxel and methotrexate) would facilitate contamination comparisons amongst studies and local results. Most recent studies reported thresholds for cyclophosphamide close to 0.1 ng/cm² at the 90 th percentile. ConclusionsThe overall risk of exposure for healthcare professionals is a major concern. Sample size in multicentric studies would require at least 500 samples; quantification of all tracers with the highest contamination frequencies need to be quantified. This approach would provide a basis to develop guidelines to appropriately monitor contamination in pharmacies and patient care area managers.

01 Apr 2025·Current Problems in Cancer

Comparison of efficacy and toxicity of chemotherapeutic regimens used as adjuvant and/or neoadjuvant chemotherapy in penile cancer patients

Article

Author: Jha, Ambika Nand ; Gupta, Ashok Kumar ; Dhasthakeer, Usman

OBJECTIVETo compare the efficacy and toxicity of different chemotherapeutic regimens used as adjuvant or neoadjuvant chemotherapy in penile cancer patients.METHODOLOGYThis observational study was carried out at Mahavir Cancer Sansthan & Research Centre (MCSRC), Patna, involving 112 patients who received various chemotherapy regimens: 5-Fluorouracil with Cisplatin (FP), Paclitaxel with Carboplatin (TP₁), Paclitaxel with Cisplatin (TP₂), and Paclitaxel with Ifosfamide and Cisplatin (TIP). Efficacy was assessed based on tumor response after Neoadjuvant Chemotherapy (NACT) using RECIST v1.1, and Disease-Free Survival (DFS) was calculated with the Kaplan-Meier method. Chemotherapy toxicity was evaluated using CTCAE v4.03, and statistical analysis was performed with SPSS v22.RESULTSThe mean age of the penile cancer patients was found to be 53.5 years. The most of the patients comes under stage-IIIb (62 patients - 55.4%). Out of 88 FP received patients, 28 were treated with NACT in which 24 had partial response (PR) and 4 had progressive disease (PD). The objective response rate (ORR) for this group was found to be 85.71%. Out of 21 TP₁ received patients, 9 were treated with NACT in which 6 had CR and 3 had PR, therefore ORR was found to be 100%. Only one Patient received TIP as NACT had PR. The median DFS rate was found to be 6 months for ACT and 7 months for NACT in FP chemotherapy, whereas 10 months was found to be for ACT and NACT of TP₁ combinations. The patients received TP₁ combinations, had more than 6 months of DFS rate. The grade I-III haematological toxicity of anaemia, lymphocytopenia and thrombocytopenia was observed more in FP than TP₁ and TP₂ combinations. The grade I-III non-haematological toxicity was showed for all chemotherapy combinations.CONCLUSIONOverall, the TP₁ regimen stands out as the most effective and well-tolerated chemotherapy regimen for penile cancer, demonstrating both superior survival outcomes and a more favourable toxicity profile compared to the FP regimen.

01 Apr 2025·Pediatric Blood & Cancer

Results of the Latin American Pediatric Oncology Group (GALOP‐2011) Trial for Patients With Localized Ewing Sarcoma: A Multicentric Study of Interval‐Compressed Multiagent Chemotherapy

Article

Author: Rose, Adriana ; Siqueira, Laurice ; Santos Pestilho, Julie Francine Cerutti ; Villarroel, Milena ; Salgado, Carmen ; da Costa, Gildene Alves ; Brunetto, Algemir Lunardi ; Almeida, Maria Tereza ; Castillo, Luis ; Gregianin, Lauro José

ABSTRACTBackgroundGALOP investigators developed a prospective cooperative protocol for localized Ewing sarcoma (ES) incorporating interval‐compressed chemotherapy (VDC/IE, vincristine, doxorubicin, cyclophosphamide/ifosfamide and etoposide). After completing conventional treatment, patients were randomized to 1 year of metronomic chemotherapy (vinblastine and cyclophosphamide).MethodsPhase III randomized prospective trial. Induction consisted of six alternating cycles of VDC/IE every 14 days, followed by local control, and eight cycles of consolidation every 21 days. After consolidation, patients were randomized 1:1 to metronomic chemotherapy or stop treatment, balanced by age (>/< 14 years‐old), sex (M/F), site (pelvic/non‐pelvic), and size (>/< 8 cm). The results of randomization will be published elsewhere with longer follow‐up.ResultsBetween 2011 and 2019, 315 patients (59.7% male, median age 11.0 years) were recruited across 34 centers in Argentina, Brazil, Chile, and Uruguay. The most frequent localizations were axial (45.1%), extremity (38.1%), and pelvic (16.8%). The median time interval between cycles was 19 and 22 days at induction and consolidation, respectively. There were no unexpected toxicity or toxic deaths related to interval compression. The overall response rate post‐induction was 81.6%. Local treatment with surgery (50.8%), radiotherapy (19.7%), or a combination (26%) was performed in 304 (96.5%) patients. With a median follow‐up of 50 months (range: 1.67–121.7), the 5‐year overall and event‐free survivals were 68.6% (SE: 0.030) and 63.7% (SE: 0.029), respectively.ConclusionImplementation of a multi‐institutional protocol with the strategy of interval‐compressed induction for ES in South America was feasible with favorable results. This success is attributed to rigorous protocol adherence, extensive educational efforts, and a strong emphasis on data quality maintenance, demonstrating a reproducible model for countries with similar resource limitations.

News (Medical) associated with Ifosamide

05 Nov 2024

·www.businesswire.com

Genentech to Present New and Encouraging Long-term Follow-up Data Across Broad Hematology Portfolio at ASH 2024

SOUTH SAN FRANCISCO, Calif.--( BUSINESS WIRE )--Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY) announced today that it will present more than 40 abstracts across nine blood disorders at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, held December 7-10, 2024 in San Diego, California. The data underscore Genentech’s commitment to advance patient outcomes in lymphoma with long-term follow-up of its approved medicines Polivy ® (polatuzumab vedotin-piiq), Lunsumio ® (mosunetuzumab-axgb) and Columvi ® (glofitamab-gxbm) as well as new investigational combination data. Key presentations include: Five-year data from the Phase III POLARIX study (abstract #469) reinforce the potential of Polivy in combination with Rituxan ® (rituximab), cyclophosphamide, doxorubicin and prednisone (R-CHP) to provide durable and lasting remissions and for the first time show a positive trend in overall survival (OS) for people with first-line diffuse large B-cell lymphoma (DLBCL), an area that previously had little advancement in nearly two decades. Extended follow-up data of up to four years from the pivotal GO29781 study of Lunsumio (abstract #4407) and NP30179 study of Columvi (abstract #865) show long-lasting remissions and immune system recovery after the end of treatment, supporting the use of fixed-duration bispecific antibodies for third-line or later (3L+) follicular lymphoma (FL) and DLBCL, respectively. First presentation of data for a subcutaneous formulation of Lunsumio monotherapy from the pivotal Phase II GO29781 study (abstract #1645) show high rates of deep and durable responses and low rates and severity of cytokine release syndrome in people with 3L+ FL. Subcutaneously administered Lunsumio could further improve the patient experience by combining shorter administration time with the existing benefits of a fixed-duration and outpatient therapy. New patient-reported outcomes data from the Phase III STARGLO study (abstract #5132) indicate comparable health-related quality of life between treatment arms, despite higher median number of cycles received with the Columvi combination (11 versus 4). Together with the significant improvement in OS observed in the study, these data support the potential benefit for patients with second-line or later DLBCL. New and updated data from investigational study combinations of Polivy with bispecific antibodies Lunsumio and Columvi in relapsed or refractory DLBCL, including the Phase Ib/II NP39488 (abstract #988) and Phase II GO40516 (abstract #989) studies, add to the growing body of evidence demonstrating the potential of novel bispecific antibody/Polivy combinations in earlier treatment lines, and support their ongoing Phase III development. Overview of key presentations featuring Genentech medicines Medicine Abstract title Abstract number/presentation details Polivy Five-Year Analysis of the POLARIX Study: Prolonged Follow-up Confirms Positive Impact of Polatuzumab Vedotin Plus Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (Pola-R-CHP) on Outcomes #469 oral presentation Session: 626. Aggressive Lymphomas: Clinical and Epidemiological: CARs, Bispecifics, and ADCs: Progress and Challenges in Aggressive B Cell Lymphoma Sunday, December 8, 2024 9:30 AM PST A Multicenter, Prospective, Observational Study of Pola-R-CHP in Patients With Previously Untreated Diffuse Large B-Cell Lymphoma (POLASTAR): A Preliminary Analysis #4475 poster presentation Session: 626. Aggressive Lymphomas: Clinical and Epidemiological: Poster III Monday, December 9, 2024 6:00 - 8:00 PM PST Lunsumio A Randomized Phase II Study of Mosunetuzumab SC Plus Polatuzumab Vedotin Demonstrates Improved Outcomes Versus Rituximab Plus Polatuzumab Vedotin in Patients (Pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL) #989 oral presentation Session: 627. Aggressive Lymphomas: Pharmacologic Therapies: Chemotherapy-free Combinations for Relapsed Aggressive Lymphomas Monday, December 9, 2024 5:30 PM PST Subcutaneous Mosunetuzumab Leads to High Rates of Durable Responses, Low Rates of Cytokine Release Syndrome, and Non-Inferior Exposure Compared with Intravenous Administration in Patients with Relapsed/Refractory Follicular Lymphoma: Primary Analysis of a Pivotal Phase II Study #1645 poster presentation Session: 623. Mantle Cell, Follicular, Waldenstrom’s, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster I Saturday, December 7, 2024 5:30 - 7:30 PM PST Mosunetuzumab Continues to Demonstrate Clinically Meaningful Outcomes in Patients with Relapsed and/or Refractory Follicular Lymphoma after ≥2 Prior Therapies Including Those with a History of POD24: 4-Year Follow-up of a Pivotal Phase II Study #4407 poster presentation Session: 623. Mantle Cell, Follicular, Waldenstrom’s, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster III Monday, December 9, 2024 6:00 - 8:00 PM PST Mosunetuzumab Monotherapy Demonstrates Encouraging Activity and a Manageable Safety Profile in Patients with Heavily Pre-Treated Relapsed or Refractory Mantle Cell Lymphoma #1646 poster presentation Session: 623. Mantle Cell, Follicular, Waldenstrom’s, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster I Saturday, December 7, 2024 5:30 - 7:30 PM PST Fixed-Duration Subcutaneous Mosunetuzumab is Active and has a Manageable Safety Profile in Patients with Previously Untreated, Low-Tumor Burden Follicular Lymphoma: Updated Results from the Phase II MorningSun Study #3008 poster presentation Session: 623. Mantle Cell, Follicular, Waldenstrom’s, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster II Sunday, December 8, 2024 6:00 - 8:00 PM PST Travel Burden and Travel Costs of Bispecific Antibodies in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma and Relapsed/Refractory Follicular Lymphoma #782 oral presentation Session: 902. Health Services and Quality Improvement: Lymphoid Malignancies: For a Better Tomorrow - Improving Access to Blood Cancer Treatments and Trials Monday, December 9, 2024 10:45 AM PST Columvi Fixed-duration Glofitamab Monotherapy Continues to Demonstrate Durable Responses in Patients with Relapsed or Refractory Large B-Cell Lymphoma: 3-year Follow-Up From a Pivotal Phase II Study #865 oral presentation Session: 627. Aggressive Lymphomas: Pharmacologic Therapies: New R-CHOP Combinations for Treatment Naïve DLBCL Sunday, December 8, 2024 Midday PST Glofitamab in Combination with Polatuzumab Vedotin Maintains Durable Responses and a Manageable Safety Profile in Patients with Heavily Pre-treated Relapsed/Refractory (R/R) Large B-Cell Lymphoma (LBCL) Including High-Grade B-Cell Lymphoma (HGBCL): Extended Follow-Up of a Phase Ib/II Study #988 oral presentation Session: 627. Aggressive Lymphomas: Pharmacologic Therapies: Chemotherapy-free Combinations for Relapsed Aggressive Lymphomas Monday, December 9, 2024 5:15 PM PST Glofitamab in Combination with Rituximab plus Ifosfamide, Carboplatin, and Etoposide shows Favorable Efficacy and Manageable Safety in Patients with Relapsed or Refractory Diffuse Large B-cell Lymphoma, Eligible for Stem Cell Transplant or Chimeric Antigen Receptor T-cell Therapy: Results from a Phase Ib Study #987 oral presentation Session: 627. Aggressive Lymphomas: Pharmacologic Therapies: Chemotherapy-free Combinations for Relapsed Aggressive Lymphomas Monday, December 9, 2024 5:00 PM PST Primary Results of Patient-Reported Outcomes in Patients with Relapsed/Refractory Diffuse Large B-cell Lymphoma Treated with Glofitamab plus Gemcitabine and Oxaliplatin (Glofit-GemOx) Versus Rituximab plus GemOx (R-GemOx) from the Phase III STARGLO Study #5132 poster presentation Session: 906. Outcomes Research: Lymphoid Malignancies Excluding Plasma Cell Disorders: Poster III Monday, December 9, 2024 6:00 - 8:00 PM PST Glofitamab Induces High Response Rates and Durable Remissions in Patients (Pts) with Heavily Pretreated Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL), including those with a Poor Prognosis: Subgroup Results from a Phase I/II Study #1631 poster presentation Session: 623. Mantle Cell, Follicular, Waldenstrom’s, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster I Saturday, December 7, 2024 5:30 - 7:30 PM PST A Healthcare Utilization Model Comparing Time Toxicity Between Glofitamab and Epcoritamab Treatment Regimens #3647 poster presentation Session: 902. Health Services and Quality Improvement: Lymphoid Malignancies: Poster II Sunday, December 8, 2024 6:00 - 8:00 PM PST Englumafusp alfa Englumafusp Alfa (CD19-4-1BBL) Combined with Glofitamab is Safe and Efficacious in Patients with R/R B-NHL: Extended Follow Up Analysis of the Dose-Escalation Part of Phase I Trial BP41072 #990 oral presentation Session: 627. Aggressive Lymphomas: Pharmacologic Therapies: Chemotherapy-free Combinations for Relapsed Aggressive Lymphomas Monday, December 9, 2024 5:45 PM PST Cevostamab Cevostamab in Patients with Heavily Pretreated Relapsed/Refractory Multiple Myeloma (RRMM): Updated Results from an Ongoing Phase I Study Demonstrate Clinically Meaningful Activity and Manageable Safety and Inform the Doses and Regimen for Combination Studies #1021 oral presentation Session: 654. Multiple Myeloma: Pharmacologic Therapies: Into the Future: New Drugs and Combinations in Multiple Myeloma Monday, December 9, 2024 4:30 PM PST Venclexta ® (venetoclax)* CRISTALLO: Results from a Phase III Trial of Venetoclax–Obinutuzumab versus Fludarabine, Cyclophosphamide and Rituximab or Bendamustine–Rituximab in Patients with Untreated Chronic Lymphocytic Leukemia Without Del(17p) or TP53 Mutations #3237 poster presentation Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster II Sunday, December 8, 2024 6:00 - 8:00 PM PST P-CD19CD20-ALLO1 (in collaboration with Poseida Therapeutics) P-CD19CD20-ALLO1: Potent Fully Allogeneic CAR-T Therapy Targeting CD19 and CD20 with Superior Efficacy Over Single-Target Products #4805 poster presentation Session: 702. CAR-T Cell Therapies: Basic and Translational: Poster III Monday, December 9, 2024 6:00 - 8:00 PM PST P-BCMA-ALLO1 (in collaboration with Poseida Therapeutics) A Phase 1 Study of P-BCMA-ALLO1, a Non-viral, Allogeneic BCMA Directed CAR-T in Relapsed/Refractory Multiple Myeloma (RRMM): Results from Optimized Lymphodepletion Cohort #4828 poster presentation Session: 704. Cellular Immunotherapies: Early Phase Clinical Trials and Toxicities: Poster III Monday, December 9, 2024 6:00 - 8:00 PM PST Hemlibra ® (emicizumab) Bleed Patterns in Infants, From Birth to 12 Months of Age, with Hemophilia A Treated with Emicizumab: Exploratory Analysis of the HAVEN 7 Study #1214 poster presentation Session: 322. Hemophilia A and B: Clinical and Epidemiological: Poster I Saturday, December 7, 2024 5:30 - 7:30 PM PST Real-World Experience With Emicizumab for Hemophilia A From the Physician Perspective Based on Survey Data #5078 poster presentation Session: 905. Outcomes Research: Non-Malignant Conditions Excluding Hemoglobinopathies: Poster III Monday, December 9, 2024 6:00 - 8:00 PM PST PiaSky ® (crovalimab) Phase III Randomized COMMODORE 2 Trial: 2-Year Efficacy and Safety of Crovalimab in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Naive to Complement Inhibition #2687 poster presentation Session: 508. Bone Marrow Failure: Acquired: Poster II Sunday, December 8, 2024 6:00 - 8:00 PM PST Phase III COMMODORE 1 Trial: 2-Year Efficacy and Safety of Crovalimab in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Switched from Ravulizumab #4078 poster presentation Session: 508. Bone Marrow Failure: Acquired: Poster III Monday, December 9, 2024 6:00 - 8:00 PM PST *Venclexta is being developed by AbbVie and Genentech, a member of the Roche Group. It is jointly commercialized by the companies in the United States and commercialized by AbbVie outside of the United States. About Polivy ® (polatuzumab vedotin-piiq) Polivy is a first-in-class anti-CD79b antibody-drug conjugate (ADC). The CD79b protein is expressed specifically in the majority of B cells, an immune cell impacted in some types of non-Hodgkin’s lymphoma (NHL), making it a promising target for the development of new therapies. Polivy binds to cancer cells such as CD79b and destroys these B cells through the delivery of an anti-cancer agent, which is thought to minimize the effects on normal cells. Polivy is being developed by Genentech using Seagen ADC technology and is currently being investigated for the treatment of several types of NHL. Polivy U.S. Indication Polivy is a prescription medicine used with other medicines (a rituximab product, cyclophosphamide, doxorubicin, and prednisone) as a first treatment for adults who have moderate to high risk diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) or high-grade B-cell lymphoma (HGBL). Polivy is a prescription medicine used with other medicines, bendamustine and a rituximab product, to treat DLBCL in adults who have progressed after at least 2 prior therapies. Important Safety Information Possible serious side effects Everyone reacts differently to Polivy therapy, so it’s important to know what the side effects are. Some people who have been treated with Polivy have experienced serious to fatal side effects. Your doctor may stop or adjust your treatment if any serious side effects occur. Be sure to contact your healthcare team if there are any signs of these side effects. Nerve problems in your arms and legs: This may happen as early as after your first dose and may worsen with every dose. Your doctor will monitor for signs and symptoms, such as changes in your sense of touch, numbness or tingling in your hands or feet, nerve pain, burning sensation, any muscle weakness, or changes to your walking pattern Infusion-related reactions: You may experience fever, chills, rash, breathing problems, low blood pressure, or hives within 24 hours of your infusion Low blood cell counts: Treatment with Polivy can cause severe low blood cell counts. Your doctor will monitor your blood counts throughout treatment with Polivy Infections: If you have a fever of 100.4°F (38°C) or higher, chills, cough, or pain during urination, contact your healthcare team. Your doctor may also give you medication before giving you Polivy, which may prevent some infections Rare and serious brain infections: Your doctor will monitor closely for signs and symptoms of these types of infections. Contact your doctor if you experience confusion, dizziness or loss of balance, trouble talking or walking, or vision changes Tumor lysis syndrome: Caused by the fast breakdown of cancer cells. Signs include nausea, vomiting, diarrhea, and lack of energy Potential harm to liver: Some signs include tiredness, weight loss, pain in the abdomen, dark urine, and yellowing of your skin or the white part of your eyes. You may be at higher risk if you already had liver problems or you are taking other medication Side effects seen most often The most common side effects during treatment were Nerve problems in arms and legs Nausea Tiredness or lack of energy Diarrhea Constipation Hair loss Redness and sores of the lining of the mouth, lips, throat, and digestive tract Polivy may lower your red or white blood cell counts and increase uric acid levels. Polivy may not be for everyone. Talk to your doctor if you are Pregnant or think you are pregnant: Data have shown that Polivy may harm your unborn baby Planning to become pregnant: Women should avoid getting pregnant while taking Polivy. Women should use effective contraception during treatment and for 3 months after their last Polivy treatment. Men taking Polivy should use effective contraception during treatment and for 5 months after their last Polivy treatment Breastfeeding: Women should not breastfeed while taking Polivy and for 2 months after the last dose These may not be all the side effects. Talk to your healthcare provider for more information about the benefits and risks of Polivy treatment. You may report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch . You may also report side effects to Genentech at (888) 835-2555. Please see the full Prescribing Information and visit https://www.Polivy.com for additional Important Safety Information. About Lunsumio ® (mosunetuzumab-axgb) Lunsumio is a first-in-class CD20xCD3 T-cell engaging bispecific antibody designed to target CD20 on the surface of B cells and CD3 on the surface of T cells. This dual targeting activates and redirects a patient’s existing T cells to engage and eliminate target B cells by releasing cytotoxic proteins into the B cells. A robust clinical development program for Lunsumio is ongoing, investigating the molecule as a monotherapy and in combination with other medicines, for the treatment of people with B-cell non-Hodgkin’s lymphomas, including follicular lymphoma and diffuse large B-cell lymphoma, and other blood cancers. Lunsumio U.S. Indication Lunsumio (mosunetuzumab-axgb) is a prescription medicine used to treat adults with follicular lymphoma whose cancer has come back or did not respond to previous treatment, and who have already received two or more treatments for their cancer. It is not known if Lunsumio is safe and effective in children. The conditional approval of Lunsumio is based on response rate. There are ongoing studies to establish how well the drug works. What is the most important information I should know about Lunsumio? Lunsumio may cause Cytokine Release Syndrome (CRS), a serious side effect that is common during treatment with Lunsumio and can also be severe or life-threatening. Get medical help right away if you develop any signs or symptoms of CRS at any time, including: fever of 100.4°F (38°C) or higher chills low blood pressure fast or irregular heartbeat tiredness or weakness difficulty breathing headache confusion feeling anxious dizziness or light-headedness nausea vomiting Due to the risk of CRS, you will receive Lunsumio on a “step-up dosing schedule.” The step-up dosing schedule is when you receive smaller “step-up” doses of Lunsumio on Day 1 and Day 8 of your first cycle of treatment You will receive a higher dose of Lunsumio on Day 15 of your first cycle of treatment If your dose of Lunsumio is delayed for any reason, you may need to repeat the step-up dosing schedule Before each dose in Cycle 1 and Cycle 2, you will receive medicines to help reduce your risk of CRS Your healthcare provider will check you for CRS during treatment with Lunsumio and may treat you in a hospital if you develop signs and symptoms of CRS. Your healthcare provider may temporarily stop or completely stop your treatment with Lunsumio, if you have severe side effects. What are the possible side effects of Lunsumio? Lunsumio may cause serious side effects, including: Neurologic problems. Your healthcare provider will check you for neurologic problems during treatment with Lunsumio. Your healthcare provider may also refer you to a healthcare provider who specializes in neurologic problems. Tell your healthcare provider right away if you develop any signs or symptoms of neurologic problems during or after treatment with Lunsumio, including: headache numbness and tingling of the arms, legs, hands, or feet dizziness confusion and disorientation difficulty paying attention or understanding things forgetting things or forgetting who or where you are trouble speaking, reading, or writing sleepiness or trouble sleeping tremors loss of consciousness seizures muscle problems or muscle weakness loss of balance or trouble walking Serious infections. Lunsumio can cause serious infections that may lead to death. Your healthcare provider will check you for signs and symptoms of infection before and during treatment. Tell your healthcare provider right away if you develop any signs or symptoms of infection during treatment with Lunsumio, including: fever of 100.4° F (38° C) or higher chest pain tiredness shortness of breath painful rash sore throat pain during urination feeling weak or generally unwell Low blood cell counts. Low blood cell counts are common during treatment with Lunsumio and can also be severe. Your healthcare provider will check your blood cell counts during treatment with Lunsumio. Lunsumio may cause the following low blood cell counts: low white blood cell counts (neutropenia). Low white blood cells can increase your risk for infection low red blood cell counts (anemia). Low red blood cells can cause tiredness and shortness of breath low platelet counts (thrombocytopenia). Low platelet counts can cause bruising or bleeding problems Growth in your tumor or worsening of tumor related problems (Tumor flare). Lunsumio may cause serious or severe worsening of your tumor. Tell your healthcare provider if you develop any of these signs or symptoms of tumor flare during your treatment with Lunsumio: tender or swollen lymph nodes, chest pain, cough, trouble breathing, and pain or swelling at the site of the tumor Your healthcare provider may temporarily stop or permanently stop treatment with Lunsumio if you develop severe side effects. The most common side effects of Lunsumio include: tiredness, rash, fever, and headache. The most common severe abnormal lab test results with Lunsumio include: decreased phosphate, increased glucose, and increased uric acid levels. Before receiving Lunsumio, tell your healthcare provider about all of your medical conditions, including if you: have ever had an infusion reaction after receiving Lunsumio have an infection, or have had an infection in the past which lasted a long time or keeps coming back have or have had Epstein-Barr Virus are pregnant or plan to become pregnant. Lunsumio may harm your unborn baby. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with Lunsumio Females who are able to become pregnant: your healthcare provider should do a pregnancy test before you start treatment with Lunsumio you should use an effective method of birth control during your treatment and for 3 months after the last dose of Lunsumio are breastfeeding or plan to breastfeed. It is not known if Lunsumio passes into your breast milk. Do not breastfeed during treatment and for 3 months after the last dose of Lunsumio Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. What should I avoid while receiving Lunsumio? Do not drive, operate heavy machinery, or do other dangerous activities if you develop dizziness, confusion, tremors, sleepiness, or any other symptoms that impair consciousness until your signs and symptoms go away. These may be signs and symptoms of CRS or neurologic problems. These are not all the possible side effects of Lunsumio. Talk to your healthcare provider for more information about the benefits and risks of Lunsumio. You may report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch . You may also report side effects to Genentech at (888) 835-2555. Please see Important Safety Information, including Serious Side Effects, as well as the Lunsumio full Prescribing Information and Medication Guide or visit https://www.Lunsumio.com . About Columvi ® (glofitamab-gxbm) Columvi is a CD20xCD3 T-cell engaging bispecific antibody designed to target CD3 on the surface of T cells and CD20 on the surface of B cells. Columvi was designed with a novel 2:1 structural format. This T-cell engaging bispecific antibody is engineered to have one region that binds to CD3, a protein on T cells, a type of immune cell, and two regions that bind to CD20, a protein on B cells, which can be healthy or malignant. This dual-targeting brings the T cell in close proximity to the B cell, activating the release of cancer cell-killing proteins from the T cell. A clinical development program for Columvi is ongoing, investigating the molecule as a monotherapy and in combination with other medicines for the treatment of people with B-cell non-Hodgkin’s lymphomas, including diffuse large B-cell lymphoma and other blood cancers. Columvi U.S. Indication Columvi (glofitamab-gxbm) is a prescription medicine to treat adults with certain types of diffuse large B-cell lymphoma (DLBCL) or large B-cell lymphoma (LBCL) that has come back (relapsed) or that did not respond to previous treatment (refractory), and who have received 2 or more prior treatments for their cancer. It is not known if Columvi is safe and effective in children. The conditional approval of Columvi is based on response rate and durability of response. There are ongoing studies to establish how well the drug works. What is the most important information I should know about Columvi? Columvi can cause Cytokine Release Syndrome (CRS), a serious side effect that is common during treatment with Columvi, and can also be serious and lead to death. Call your healthcare provider or get emergency medical help right away if you develop any signs or symptoms of CRS, including: fever of 100.4°F (38°C) or higher chills or shaking fast or irregular heartbeat dizziness or light-headedness trouble breathing shortness of breath Due to the risk of CRS, you will receive Columvi on a “step-up dosing schedule”. A single dose of a medicine called obinutuzumab will be given to you on the first day of your first treatment cycle (Day 1 of Cycle 1). You will start the Columvi step-up dosing schedule a week after the obinutuzumab dose. The step-up dosing schedule is when you receive smaller “step-up” doses of Columvi on Day 8 and Day 15 of Cycle 1. This is to help reduce your risk of CRS. You should be hospitalized during your infusion and for 24 hours after receiving the first step-up dose on Day 8. You should be hospitalized during your infusion and for 24 hours after receiving the second step-up dose on Day 15 if you experienced CRS during the first step-up dose. You will receive your first full dose of Columvi a week after the second step-up dose (this will be Day 1 of Cycle 2). If your dose of Columvi is delayed for any reason, you may need to repeat the “step-up dosing schedule”. If you had more than mild CRS with your previous dose of Columvi, you should be hospitalized during and for 24 hours after receiving your next dose of Columvi. Before each dose of Columvi, you will receive medicines to help reduce your risk of CRS and infusion-related reactions. Your healthcare provider will monitor you for CRS during treatment with Columvi and may treat you in a hospital if you develop signs and symptoms of CRS. Your healthcare provider may temporarily stop or completely stop your treatment with Columvi if you have severe side effects. Carry the Columvi Patient Wallet Card with you at all times and show it to all of your healthcare providers. The Columvi Patient Wallet Card lists the signs and symptoms of CRS you should get emergency medical help for right away. What are the possible side effects of Columvi? Columvi may cause serious side effects, including: Cytokine Release Syndrome. Neurologic problems. Columvi can cause serious neurologic problems that may lead to death. Your healthcare provider will monitor you for neurologic problems during treatment with Columvi. Your healthcare provider may also refer you to a healthcare provider who specializes in neurologic problems. Tell your healthcare provider right away if you develop any signs or symptoms of neurologic problems, including: headache confusion and disorientation difficulty paying attention or understanding things trouble speaking sleepiness memory problems numbness, tingling, or weakness of the hands or feet dizziness shaking (tremors) Serious Infections. Columvi can cause serious infections that may lead to death. Your healthcare provider will monitor you for signs and symptoms of infection and treat you as needed. Tell your healthcare provider right away if you develop any signs of an infection, including: fever, chills, weakness, cough, shortness of breath, or sore throat. Growth in your tumor or worsening of tumor related problems (tumor flare). Tell your healthcare provider if you get any of these signs or symptoms of tumor flare: tender or swollen lymph nodes pain or swelling at the site of the tumor chest pain cough trouble breathing The most common side effects of Columvi include: CRS, muscle and bone pain, rash, and tiredness. The most common severe abnormal lab test results with Columvi include: decreased white blood cells, decreased phosphate (an electrolyte), increased uric acid levels, and decreased fibrinogen (a protein that helps with blood clotting). Your healthcare provider may temporarily stop or completely stop treatment with Columvi if you develop certain side effects. Before receiving Columvi, tell your healthcare provider about all of your medical conditions, including if you: have an infection have kidney problems are pregnant or plan to become pregnant. Columvi may harm your unborn baby Females who are able to become pregnant: Your healthcare provider should do a pregnancy test before you start treatment with Columvi. You should use effective birth control (contraception) during treatment and for 1 month after your last dose of Columvi. Talk to your healthcare provider about what birth control method is right for you during this time. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with Columvi. are breastfeeding or plan to breastfeed. Columvi may pass into your breast milk. Do not breastfeed during treatment and for 1 month after your last dose of Columvi. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. What should I avoid while receiving Columvi? Do not drive, operate heavy machinery, or do other dangerous activities if you develop dizziness, confusion, shaking (tremors), sleepiness, or any other symptoms that impair consciousness until your signs and symptoms go away. These may be signs and symptoms of neurologic problems. These are not all the possible side effects of Columvi. Talk to your health care provider for more information about the benefits and risks of Columvi. You may report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch . You may also report side effects to Genentech at (888) 835-2555. Please see Important Safety Information, including Serious Side Effects , as well as the Columvi full Prescribing Information and Medication Guide or visit https://www.Columvi.com . About Venclexta ® (venetoclax) Venclexta is a first-in-class targeted medicine designed to selectively bind and inhibit the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers and other tumors, BCL-2 builds up and prevents cancer cells from dying or self-destructing, a process called apoptosis. Venclexta blocks the BCL-2 protein and works to help restore the process of apoptosis. Venclexta is being developed by AbbVie and Genentech, a member of the Roche Group. It is jointly commercialized by the companies in the United States and commercialized by AbbVie outside of the United States. Together, the companies are committed to research with Venclexta, which is currently being studied in clinical trials across several types of blood cancers. Venclexta U.S. Indications Venclexta is a prescription medicine used: to treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). in combination with azacitidine, or decitabine, or low-dose cytarabine to treat adults with newly-diagnosed acute myeloid leukemia (AML) who: ‒ are 75 years of age or older, or ‒ have other medical conditions that prevent the use of standard chemotherapy. It is not known if Venclexta is safe and effective in children. Important Safety Information What is the most important information patients should know about Venclexta? Venclexta can cause serious side effects, including: Tumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure, the need for dialysis treatment, and may lead to death. The patient’s doctor will do tests to check their risk of getting TLS before they start taking Venclexta. The patient will receive other medicines before starting and during treatment with Venclexta to help reduce the risk of TLS. The patient may also need to receive intravenous (IV) fluids into their vein. The patient’s doctor will do blood tests to check for TLS when the patient first starts treatment and during treatment with Venclexta. It is important for patients to keep appointments for blood tests. Patients should tell their doctor right away if they have any symptoms of TLS during treatment with Venclexta, including fever, chills, nausea, vomiting, confusion, shortness of breath, seizures, irregular heartbeat, dark or cloudy urine, unusual tiredness, or muscle or joint pain. Patients should drink plenty of water during treatment with Venclexta to help reduce the risk of getting TLS. Patients should drink 6 to 8 glasses (about 56 ounces total) of water each day, starting 2 days before the first dose on the day of the first dose of Venclexta, and each time a dose is increased. The patient’s doctor may delay, decrease the dose, or stop treatment with Venclexta if the patient has side effects. When restarting Venclexta after stopping for 1 week or longer, the patient’s doctor may again check for the risk of TLS and change the patient’s dose. What patients should not take Venclexta? Certain medicines must not be taken when the patient first starts taking Venclexta and while the dose is being slowly increased because of the risk of increased TLS. Patients should tell their doctor about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Venclexta and other medicines may affect each other causing serious side effects. Patients must not start new medicines during treatment with Venclexta without first talking with their doctor. Before taking Venclexta, patients must tell their doctor about all of their medical conditions, including if they: Have kidney or liver problems. Have problems with body salts or electrolytes, such as potassium, phosphorus, or calcium. Have a history of high uric acid levels in the blood or gout. Are scheduled to receive a vaccine. Patients should not receive a “live vaccine” before, during, or after treatment with Venclexta, until the patient’s doctor tells them it is okay. If the patient is not sure about the type of immunization or vaccine, the patient should ask their doctor. These vaccines may not be safe or may not work as well during treatment with Venclexta. Are pregnant or plan to become pregnant. Venclexta may harm an unborn baby. If the patient is able to become pregnant, the patient’s doctor should do a pregnancy test before the patient starts treatment with Venclexta, and the patient should use effective birth control during treatment and for at least 30 days after the last dose of Venclexta. If the patient becomes pregnant or thinks they are pregnant, the patient should tell their doctor right away. Are breastfeeding or plan to breastfeed. It is not known if Venclexta passes into the patient’s breast milk. Patients are instructed to not breastfeed during treatment with Venclexta and for 1 week after the last dose. What to avoid while taking Venclexta: Patients should not drink grapefruit juice or eat grapefruit, Seville oranges (often used in marmalades), or starfruit while they are taking Venclexta. These products may increase the amount of Venclexta in the patient’s blood. What are the possible side effects of Venclexta? Venclexta can cause serious side effects, including: Low white blood cell counts (neutropenia). Low white blood cell counts are common with Venclexta, but can also be severe. The patient’s doctor will do blood tests to check their blood counts during treatment with Venclexta and may pause dosing. Infections. Death and serious infections such as pneumonia and blood infection (sepsis) have happened during treatment with Venclexta. The patient’s doctor will closely monitor and treat the patient right away if they have a fever or any signs of infection during treatment with Venclexta. Patients should tell their doctor right away if they have a fever or any signs of an infection during treatment with Venclexta. The most common side effects of Venclexta when used in combination with obinutuzumab or rituximab or alone in people with CLL or SLL include low white blood cell count; low platelet count; low red blood cell count; diarrhea; nausea; upper respiratory tract infection; cough; muscle and joint pain; tiredness; and swelling of arms, legs, hands, and feet. The most common side effects of Venclexta in combination with azacitidine or decitabine or low-dose cytarabine in people with AML include nausea; diarrhea; low platelet count; constipation; low white blood cell count; fever with low white blood cell count; tiredness; vomiting; swelling of arms, legs, hands, or feet; fever; infection in lungs; shortness of breath; bleeding; low red blood cell count; rash; stomach (abdominal) pain; infection in your blood; muscle and joint pain; dizziness; cough; sore throat; and low blood pressure. Venclexta may cause fertility problems in males. This may affect the ability to father a child. Patients should talk to their doctor if they have concerns about fertility. These are not all the possible side effects of Venclexta. Patients should call their doctor for medical advice about side effects. Report side effects to the FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch . Report side effects to Genentech at 1-888-835-2555. Please see the Venclexta full Prescribing Information , including the Medication Guide , for additional Important Safety Information or visit https://www.venclexta.com/ . About Hemlibra Hemlibra is a bispecific factor IXa- and factor X-directed antibody. It is designed to bring together factor IXa and factor X, proteins required to activate the natural coagulation cascade and restore the blood clotting process for hemophilia A patients. Hemlibra is a prophylactic (preventative) treatment that can be administered by an injection of a ready-to-use solution under the skin (subcutaneously) once weekly, every two weeks or every four weeks. Hemlibra was created by Chugai Pharmaceutical Co., Ltd. and is being co-developed globally by Chugai, Roche and Genentech . Hemlibra U.S. Indication Hemlibra is a prescription medicine used for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children, ages newborn and older, with hemophilia A with or without factor VIII inhibitors. Important Safety Information What is the most important information to know about Hemlibra? Hemlibra increases the potential for blood to clot. People who use activated prothrombin complex concentrate (aPCC; Feiba ® ) to treat breakthrough bleeds while taking Hemlibra may be at risk of serious side effects related to blood clots. These serious side effects include: Thrombotic microangiopathy (TMA), a condition involving blood clots and injury to small blood vessels that may cause harm to one’s kidneys, brain, and other organs Blood clots (thrombotic events), which may form in blood vessels in the arm, leg, lung, or head Patients should talk to their doctor about the signs and symptoms of these serious side effects, which can include Confusion Stomach, chest, or back pain Weakness Nausea or vomiting Swelling, pain, or redness Feeling sick or faint Decreased urination Swelling of arms and legs Yellowing of skin and eyes Eye pain, swelling, or trouble seeing Fast heart rate Numbness in your face Headache Shortness of breath Coughing up blood If patients experience any of these symptoms during or after treatment with Hemlibra, they should get medical help right away. Patients should carefully follow their healthcare provider’s instructions regarding when to use an on demand bypassing agent or factor VIII, and the dose and schedule to use for breakthrough bleed treatment. If aPCC (Feiba ® ) is needed, patients should talk to their healthcare provider in case they feel they need more than 100 U/kg of aPCC (Feiba ® ) total. Patients’ bodies may make antibodies against Hemlibra, which may stop Hemlibra from working properly. Patients should contact their healthcare provider immediately if they notice that Hemlibra has stopped working for them (e.g., increase in bleeds). The most common side effects of Hemlibra include: injection site reactions (redness, tenderness, warmth, or itching at the site of injection), headache, and joint pain. These are not all of the possible side effects of Hemlibra. Patients can speak with their healthcare provider for more information. What else should patients know about Hemlibra? Patients should see the detailed “Instructions for Use” that comes with Hemlibra for information on how to prepare and inject a dose of Hemlibra, and how to properly throw away (dispose of) used needles and syringes. Patients should stop taking their prophylactic bypassing therapy the day before they start Hemlibra Patients may continue taking their prophylactic factor VIII for the first week of Hemlibra Hemlibra may interfere with laboratory tests that measure how well blood is clotting and create an inaccurate result. Patients should speak with their healthcare provider about how this may affect their care. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Patients should only use Hemlibra for the condition it was prescribed. Patients should not give Hemlibra to other people, even if they have the same symptoms that they have. It may harm them. Patients should tell their healthcare provider about all the medicines they take , including prescription medicines, over-the-counter medicines, vitamins, or herbal supplements. Patients should keep a list of them to show their healthcare provider and pharmacist. Before using Hemlibra, patients should tell their healthcare provider about all of their medical conditions , including if they are pregnant, plan to become pregnant, are breastfeeding, or plan to breastfeed. Since Hemlibra was tested in males, there is no information on whether Hemlibra may impact an unborn baby or breast milk. Females who are able to become pregnant should use birth control during treatment. Side effects may be reported to the FDA at (800) FDA-1088 or www.fda.gov/medwatch . Side effects may also be reported to Genentech at (888) 835-2555. Please see Important Safety Information, including Serious Side Effects, as well as the Hemlibra full Prescribing Information and Medication Guide or visit https://www.hemlibra.com/ . Indications & Important Safety Information What is PIASKY? PIASKY is a prescription medicine used to treat a disease called paroxysmal nocturnal hemoglobinuria (PNH) in adults and children 13 years of age or older who weigh at least 88 pounds (40 kg). It is not known if PIASKY is safe and effective in children under 13 years of age and in people who weigh less than 88 pounds (40kg). What is the most important information I should know about PIASKY? PIASKY is a medicine that can affect your immune system. PIASKY may lower the ability of your immune system to fight infections PIASKY increases your chance of getting serious infections caused by Neisseria meningitidis . Meningococcal infections may quickly become life-threatening or cause death if not recognized and treated early. You must complete or update your meningococcal vaccines at least 2 weeks before your first dose of PIASKY. If your healthcare provider decides that immediate treatment with PIASKY is needed and your meningococcal vaccination is not up to date, you should receive meningococcal vaccination as soon as possible, and receive antibiotics for as long as your healthcare provider tells you. If you have been given a meningococcal vaccine in the past, you might need additional vaccines before starting PIASKY. Your healthcare provider will decide if you need additional meningococcal vaccine. Meningococcal vaccines do not prevent all meningococcal infections. Call your healthcare provider or get emergency medical care right away if you get any of these signs and symptoms of a serious meningococcal infection: fever fever and a rash fever with a high heart rate fever with a headache headache with nausea or vomiting headache with a stiff neck or stiff back confusion muscle aches, with flu-like symptoms eyes sensitive to light Your healthcare provider will give you a Patient Safety Card about the risk of serious meningococcal infection. Carry it with you at all times during treatment and for 11 months after your last dose of PIASKY. Your risk of meningococcal infection may continue for several months after your last dose of PIASKY. It is important to show this card to any healthcare provider who treats you. This will help them diagnose and treat you quickly. PIASKY is only available through a program called the PIASKY Risk Evaluation and Mitigation Strategy (PIASKY REMS). Before you can receive PIASKY, your healthcare provider must: enroll in the PIASKY REMS program. counsel you about the risk of serious meningococcal infection. give you information about the signs and symptoms of serious meningococcal infection. make sure that you are vaccinated with a meningococcal vaccine and that you receive antibiotics if you need to start PIASKY right away if you are not up to date on your vaccines. give you a Patient Safety Card about your risk of meningococcal infection. Immune system reactions called Type III hypersensitivity reactions are common during treatment with PIASKY and can be serious. If you are currently being treated with or have been treated with another C5 inhibitor medicine and you switch to PIASKY , PIASKY may cause Type III hypersensitivity reactions. People may also develop Type III hypersensitivity reactions when they switch from PIASKY to another C5 inhibitor medicine. If you have been treated with another C5 inhibitor medicine and you switch to PIASKY, or if you have been treated with PIASKY and you switch to another C5 inhibitor medicine, your healthcare provider should monitor you for 30 days after you switch medicines. Call your healthcare provider or go to the nearest emergency room right away if you have any signs or symptoms of Type III hypersensitivity reaction including: joint pain muscle or bone pain rash or skin problems itching headache kidney problems numbness and tingling or a feeling of pins and needles especially of the hands and feet fever weakness, tiredness, or lack of energy stomach trouble or pain PIASKY may also increase the risk of other types of serious infections , including infections caused by Neisseria spp. , Streptococcus pneumoniae , Haemophilus influenzae , and Neisseria gonorrhoeae . If you receive treatment with PIASKY, you should receive vaccines against Streptococcus pneumoniae . If your child receives treatment with PIASKY, your child should receive vaccines against Streptococcus pneumoniae and may receive vaccines against Haemophilus influenzae , depending on their age. Call your healthcare provider right away if you have any new signs or symptoms of infection such as: fever of 100.4°F (38°C) or higher cough chest pain tiredness feeling short of breath painful rash sore throat burning pain when passing urine feeling weak or generally unwell Who should not receive PIASKY? Do not receive PIASKY if you: Have a serious meningococcal infection caused by Neisseria meningitidis when you are starting PIASKY treatment. Are allergic to crovalimab or any of the ingredients in PIASKY. Before receiving PIASKY tell your healthcare provider about all of your medical conditions, including if you: have an infection or fever. are pregnant or plan to become pregnant. It is not known if PIASKY may harm your unborn baby. are breastfeeding or plan to breastfeed. It is not known if PIASKY passes into your breast milk. Tell your healthcare provider about all the medicines you take , including prescription and over-the-counter medicines, vitamins, and herbal supplements. PIASKY and other medicines can affect each other, causing side effects. Especially tell your healthcare provider if you are currently being treated with or have ever been treated with any other complementary C5 inhibitor (C5 inhibitor) medicine. PIASKY is a C5 inhibitor medicine. Know the medicines you take and the vaccines you receive. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. How should I receive PIASKY? Your healthcare provider will give you your PIASKY treatment. Your first dose will be given through a vein by intravenous (IV) infusion on Day 1 by your healthcare provider. This is the first loading dose. Another loading dose will be given as an injection under the skin (subcutaneous) on Days 2, 8, 15, and 22. Your maintenance doses will begin on Day 29 and then will be given every 4 weeks as a subcutaneous injection. Your healthcare provider will prescribe the dose based on your weight. If your weight changes, tell your healthcare provider. Talk to your healthcare provider if you miss receiving your dose of PIASKY. If you are changing treatment from another C5 inhibitor such as eculizumab or ravulizumab to PIASKY , you should receive your first loading dose of PIASKY no sooner than the time you would have received your next scheduled dose of eculizumab or ravulizumab. If you stop taking PIASKY and do not switch to another treatment for your PNH, your healthcare provider will need to monitor you closely for at least 20 weeks after stopping PIASKY. Stopping treatment with PIASKY may cause a breakdown of red blood cells due to PNH. Symptoms or problems that can happen due to red blood cell breakdown include: a lower number of red blood cells (anemia) blood in your urine or dark urine feeling short of breath feeling tired or low energy (fatigue) stomach pain blood clotting (thrombosis) difficulty swallowing difficulty getting or keeping an erection (erectile dysfunction) kidneys not working properly What are the possible side effects of PIASKY? PIASKY can cause serious side effects including: Infusion- and injection-related reactions. Infusion- or injection-related reactions may happen during or after your PIASKY administration. Symptoms may include headache, pain at infusion or injection site or in other parts of your body, swelling, bruising or bleeding, red skin, itching and rash. PIASKY can also cause serious allergic reactions. Tell your healthcare provider right away or go to the nearest emergency room if you get any of the following symptoms or symptoms of a serious allergic reaction: shortness of breath or trouble breathing pain or tightness in your chest wheezing feeling dizzy or lightheaded swelling of the throat, lips, tongue, or face skin itching, hives, or rash fever or chills The most common side effects of PIASKY are: infusion-related reactions respiratory tract infections including infections of the lungs, cold symptoms, and pain or swelling of the nose or throat viral infections Type III hypersensitivity reactions Tell your healthcare provider about any side effect that bothers you or that does not go away. These are not all the possible side effects of PIASKY. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . You may also report side effects to Genentech at (888) 835-2555. Please see the full Prescribing Information and Medication Guide for additional Important Safety Information, including Serious Side Effects , or visit https://www.piasky.com/ . About Genentech in Hematology For more than 20 years, Genentech has been developing medicines with the goal to redefine treatment in hematology. Today, we’re investing more than ever in our effort to bring innovative treatment options to people with diseases of the blood. For more information visit http://www.gene.com/hematology . About Genentech Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com .

Phase 2Clinical ResultPhase 3Phase 1ASH

09 Sep 2024

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"Overturning" the B7H3 Target: Can Its Potential be Transformed with ADC Drugs?

B7-H3 (also known as CD276) is a type I transmembrane glycoprotein and a member of the B7 family. It has no expression in monocytes, granulocytes, and normal human tissues but is expressed in some dendritic cells, T cells, natural killer (NK) cells, and B cells, making it a newly discovered immune checkpoint. This target not only facilitates immune escape of tumor cells by inhibiting the immune system but also promotes cancer progression through mechanisms of tumor metastasis, drug resistance, and angiogenesis in non-immune pathways. Studies have found that B7-H3 is abundantly expressed in several tumor tissues such as non-small cell lung cancer, pancreatic cancer, primary liver cancer, colorectal cancer, breast cancer, prostate cancer, pharyngeal cancer, melanoma, etc. Its abundant expression in tumor tissues often accompanies poor prognosis in patients, shorter overall survival period, and progression-free survival. Current B7H3 Drug Development ScenarioAccording to an incomplete count, there are over a hundred drugs targeting B7-H3 under research. They include monoclonal antibodies, bispecific antibodies, antibody-drug conjugates (ADC), antibody-linked nuclides, cellular therapies, fusion proteins, etc.; none of which have been approved yet. However, the development of drugs targeting B7-H3 has not been smooth sailing. Several clinical trials have been halted, and patient deaths have posed obstacles. For instance, in January 2019, the FDA suspended a Phase I trial for the CD3/B7H3 bispecific antibody MGD009 to treat B7H3-positive solid tumors due to the occurrence of liver-related adverse events. In 2022, enoblituzumab（MGA271）, a B7H3 monoclonal antibody, developed by I-MAB/MacroGenics was halted as patients died during the Phase II trial for advanced head and neck cancer. Additionally, the study of Macrogenics' B7H3 targeted ADC drug, vobramitamab duocarmazine (MGC-018) was also halted due to patient death and severe adverse events in the Phase II clinical trial for prostate cancer. B7H3 Trade StatusDespite these difficulties, deals for B7-H3 drugs have not decreased. According to an incomplete estimate, there have been 18 trades regarding the B7H3 target so far. Taking the past two years as an example: In July 2024, Biocytogen and IDEAYA Biosciences reached an option and licensing agreement for their BsADC project targeting B7H3/PTK7. The potential total transaction reaches 406.5 million USD, which includes 100 million USD in clinical development and regulatory milestone payments. In July 2024, Escugen and Innolake Biopharm agreed on an exclusive global license for using Escugen’s new ADC technology platform EZWi-Fit® to develop ADC products targeting specific targets. Meanwhile, Innovent's ground-breaking bispecific ADC product ILB-3103 that was designed using the EZWi-Fit® technology has successfully completed pharmacological verification of PCC (preclinical candidate compounds). This product targets DLL-3 and B7H3, two promising tumor-related targets.In December 2023, Hansoh Pharma and GSK have reached an exclusive licensing agreement on HS-20093, a B7H3 ADC drug independently developed by Hansoh Pharma. Hansoh Pharmaceuticals will grant GSK the exclusive rights to develop, manufacture, and commercialize HS-20093 globally (excluding Mainland China, Hong Kong, Macau, and Taiwan). According to the agreement, Hansoh will receive an upfront payment of $185 million and is eligible to receive up to $1.525 billion in success milestone payments. Upon commercialization of the product, GSK will also pay tiered royalty fees based on net sales outside of Mainland China, Hong Kong, Macau, and Taiwan.In October 2023, Daiichi Sankyo and Merck reached a global development and commercialization agreement for Daiichi Sankyo's three ADC candidate drugs: patritumab deruxtecan (HER3-DXd), ifinatamab deruxtecan (I-DXd), and raludotatug deruxtecan (R-DXd). They will develop and potentially commercialize these candidate ADC therapies globally. Daiichi Sankyo will retain exclusive rights in Japan and will be fully responsible for the production and supply. The potential transaction value for the three projects is up to $22 billion, among which ifinatamab deruxtecan is a B7H3-targeting ADC drug.In April 2023, BioNTech and DualityBio reached an exclusive licensing and collaboration agreement on two ADC pipelines, DB-1303 and DB-1311. Under the agreement, DualityBio will receive an upfront payment of $170 million and is expected to earn over $1.5 billion in milestone payments for development, registration, and commercialization, as well as a percentage of future potential sales in the single to double-digits as royalty fees. DB-1311 is a B7-H3-targeting antibody-conjugated drug.Which advantages do these targeted B7H3 ADC drugs have that are worth large pharmaceutical companies' investments? We will provide a brief analysis for some representative drugs. Latest Advances in B7H3 ADCsAccording to incomplete statistics, there are approximately 33 B7H3 ADC drugs currently in research, and around 14 drugs are in clinical research stages. 1.Ifinatamab Deruxtecan Ifinatamab Deruxtecan (I-DXd，DS-7300a), an ADC targeting B7-H3, is exclusively designed with Daiichi Sankyo DXd ADC technology. It consists of a humanized anti-B7-H3 IgG1 monoclonal antibody coupled with a cleavable tetrapeptide linker and Topoisomerase I inhibitor payload (a derivative of Exatecan, DXd). It is currently in phase III of clinical trials. According to data presented at the IASLC 2023 World Lung Cancer Conference, sub-group analyses of phase 1/2 trials of ifinatamab deruxtecan for treating SCLC revealed an objective response rate of 52.4%, median progression-free survival of 5.6 months, and overall survival of 12.2 months. In July 2024, it was shown on the Chinese Clinical Trial Registry that the company had registered DS-7300a for Phase III clinical trials. The aim is to compare the safety and efficacy of DS-7300a with treatments chosen by physicians in recurring small cell lung cancer (SCLC) trial participants. 2.HS-20093 Developed by Hansoh Pharma, HS-20093, a novel ADC targeting B7-H3, is composed of a humanized anti-B7-H3 monoclonal antibody covalently linked to a Topoisomerase I inhibitor (TOPOi) payload. Currently, several phase I and II clinical trials are underway in China to treat various cancers, including lung cancer, sarcoma, head and neck cancer, and other solid tumors. At the 2024 ASCO, the therapeutic potential of HS-20093 in small-cell lung cancer and osteosarcoma was showcased. Firstly, the company revealed research data from the phase II trial, ARTEMIS-002, for the treatment of relapsed/refractory osteosarcoma patients. From June to December 2023, a total of 34 relapsed/refractory osteosarcoma patients were enrolled and received HS-20093 doses of 8.0mg/kg (N=15) or 12.0mg/kg (N=19). At baseline, most patients had stage IV disease and lung metastases. Among them, 22 patients (64.7%) had received ≥3 types of previous treatments. 26 patients (76.5%) received 4 types of standard therapies including platinum complex, anthracyclines, ifosfamide, and methotrexate. As of December 25, 2023, 10 patients treated with 12.0 mg/kg HS-20093 had an objective response rate (ORR) of 20.0%; two confirmed partial responses were noted in the 12.0mg/kg group, with the longest response lasting for 4.0 months. The disease control rate for patients in the 8 mg/kg HS-20093 treatment group was 81.8% (9/11) and 100% (10/10) for those in the 12.0 mg/kg HS-20093 treatment group. The median progression-free survival of all 21 patients was not yet mature. In terms of safety, 33 patients experienced treatment-emergent adverse events (TEAEs); the most common grade 3/4 TEAEs were neutropenia, leukopenia, thrombocytopenia, lymphopenia, and anemia. No deaths caused by TEAEs were reported. Secondly, the company revealed results on the efficacy and safety of extended dose for SCLC patients previously treated with platinum standard. Data was collected until November 30, 2023, with relapsed treatments completed. In post-baseline scans, 96.2% (50/52) of patients showed a reduction in target tumor lesions, and 44.2% (23/52) had deep remission, defined as a tumor shrinkage of ≥50%. The median overall survival was not yet reached. Regardless of B7-H3 expression, a response was noted in all patients. Pharmacokinetics (PK) showed that exposure increased roughly proportionate with the dosage, with a half-life of 3-7 days. The PK curves of total antibodies and ADC were similar and effective payload exposure was relatively low. Safety was consistent with previous reports; the most common grade ≥3 treatment-related adverse events (≥10%) were neutropenia, leukopenia, lymphopenia, thrombocytopenia, and anemia. 3.Vobramitamab Duocarmazine Vobramitamab duocarmazine (MGC-018) is an ADC drug independently developed by MacroGenics. It is composed of a humanized B7-H3 monoclonal antibody, a cleavable linker, and the toxic drug Duocarmycin (DUBA). It can disrupt DNA in dividing and non-dividing cells, thereby causing cell death. It is proposed for the treatment of B7-H3 positive solid tumors. According to previously published data, in phase I/II dose-escalation and cohort expansion studies: in the dose-escalation part, among 9 prostate cancer patients, 5 exhibited a ≥50% decrease in prostate specific antigen (PSA) levels during treatment, and 2 patients had reduced target lesions (one reduced by 29%). The recommended phase II dose (RP2D) is 3mg/kg, IV, Q3W. In the cohort expansion part, among 16 evaluable patients, 4 (25%) had a reduction in target lesions by more than 30% (2 confirmed for PR, 2 unconfirmed for PR), and 21 out of 39 evaluable patients (53.8%) had a PSA reduction of over 50%. A total of 83 patients (96.5%) experienced at least one treatment-emergent adverse event. The most common treatment-related adverse events (TRAEs) (with an incidence rate of at least 20%) were fatigue, neutropenia, hand-foot syndrome, pleural effusion, nausea, and weakness. Febrile neutropenia was not reported. The safety was manageable. 4.YL201 YL201 is a B7H3-targeted ADC drug, developed using the proprietary TMALIN® technology platform by MediLink Therapeutics. This B7-H3 target is highly expressed in esophageal cancer, and with the tumor microenvironment and traditional lysosome extracellular and intracellular dual-dissolution mechanism of MediLink 's TMALIN® technology, YL201 effectively kills esophageal cancer cells which is reflected in pre-clinical and clinical trial data. Currently, the YL201 project is carrying out dose-expansion studies in multiple cancers in China and the US, including further efficacy exploration in esophageal cancer indications. 5.MHB088C MHB088C is an Antibody-Drug Conjugate (ADC) targeting B7H3, comprising of humanized anti-B7H3 monoclonal antibody coupled with a highly effective DNA topoisomerase I inhibitor that is 5 to 10 times stronger than DXd. Preclinical studies show that MHB088C possesses potent binding affinity, excellent internalization rate, and strong tumor-killing activity; it is 3 to 10 times stronger than DS-7300a analog in CDX models. Toxicology studies revealed no particular toxicity or interstitial lung disease (ILD) incidence with MHB088C, compared to other B7H3 ADCs. According to the phase 1/2 study disclosed at 2024 ASCO, the trial recruited patients with recurrent/metastatic solid tumors, divided into two stages: Dose Escalation (D-esc) and Dose Expansion (D-exp). During the D-esc stage, MHB088C was administered intravenously at doses of 0.8, 1.6, 3.0 mg/kg Q2W; 3.0, 4.0 mg/kg Q3W. Results showed that as of December 31, 2023, among 12 evaluable patients, 5 displayed Partial Responses (PRs), with an Objective Response Rate (ORR) of 41.7%, and a Disease Control Rate (DCR) of 91.7%. Among 3 SCLC patients, all reached PRs, hence an ORR of 100.0%, with one achieving Complete Response (CR) and another showing nearly 80% tumor volume reduction. The efficacy in 2 SCLC patients was achieved in the 1.6 mg/kg Q2W group. All SCLC patients showed response at the first tumor evaluation. The most common Treatment-Related Adverse Events (TRAEs) observed in ≥25% of patients were decreased neutrophil count, decreased lymphocyte count, and decreased white blood cell (WBC) count. The most common Grade ≥3 TRAEs (in ≥5% of patients) were decreased neutrophil count (33.3%), decreased lymphocyte count (30.0%), decreased WBC count (26.7%), decreased platelet count (23.3%), and anemia (15.0%). No reports of ILD were made. 6.DB-1311 DB-1311, the third-generation ADC product based on Duality Biologics's unique DITAC technology platform, exhibited powerful antitumor activity in various tumor models and demonstrated good safety and promising pharmacokinetic features in preclinical safety evaluations. Currently, the company is conducting a Phase I/IIa multi-center, open-label, first-in-human study evaluating DB-1311's safety, tolerability, pharmacokinetics, and preliminary anticancer activity in patients with advanced/metastatic solid tumors. In June 2024, the FDA granted BNT324/DB-1311 Fast Track designation for the treatment of patients with metastatic/unresectable castration-resistant prostate cancer (CRPC) showing disease progression during or after standard systemic therapy. 7.7MW3711 7MW3711, developed by Mabwell based on the novel antibody-drug conjugate technology platform IDDC™ (Interchain-Disulfide Drug Conjugate), consists of an innovative antibody molecule, a novel linker, and a novel Payload (Topoisomerase I inhibitor), and possesses full intellectual property rights. After injection into the human body, 7MW3711 can bind to tumor cell surface antigens, enter tumor cells, and release small molecules targetedly through specific enzymatic actions, thereby achieving precise tumor destruction. 8.IBI3001 IBI3001 is a potentially world-first dual-specific ADC targeting B7-H3 and EGFR, using the clinic-validated SYNtecanE® site-specific conjugation platform, and possesses multiple antitumor mechanisms: (1) enhanced EGFR signal blocking; (2) EGFR and B7-H3-mediated drug endocytosis and cytotoxicity; (3) powerful ADC bystander effects. The optimized B7-H3 arm not only strengthens the effect of EGFR signal blocking, but also reduces the toxicity of the EGFR target. In multiple in vitro and in vivo tumor models, IBI3001 has demonstrated potent tumor-killing effects and high tolerability, with a treatment window up to 40-fold. 9.ILB-3101 ILB-3101 is an antibody-drug conjugate targeting B7H3, developed based on Innolake's proprietary antibody and ADC platforms, and owns full, independent intellectual property rights. The antibody of B7H3, screened and optimized by the drug, has significant advantages over the B7H3 antibody used by leading international benchmark ADC products in key indicators such as internalization and in vitro and in vivo pharmacodynamics tests. For linker-effective payload, Innolake has selected a uniquely toxic payload substance, which offers higher efficacy and better safety than vinblastine type toxins (such as Dxd). Its linker is specifically designed, highly stable in plasma and possesses independent intellectual property rights. In preclinical CDX studies, ILB-3101 has demonstrated superior antitumor effects compared to two leading international B7H3 ADC products. In pre-toxicological studies in crab-eating macaques, ILB-3101 also exhibited a wider therapeutic window. How to obtain the latest research advancements in the field of biopharmaceuticals? In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery!

09 Aug 2024

·www.fda.gov

FDA grants accelerated approval to afamitresgene autoleucel for unresectable or metastatic synovial sarcoma

On August 2, 2024, the Food and Drug Administration granted accelerated approval to afamitresgene autoleucel (TECELRA, Adaptimmune, LLC), a melanoma-associated antigen A4 (MAGE-A4)-directed genetically modified autologous T cell immunotherapy, for adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are HLA-A*02:01P, -A*02:02P, -A*02:03P, or -A*02:06P positive and whose tumor expresses the MAGE-A4 antigen as determined by FDA-approved or cleared companion diagnostic devices. Full prescribing information for TECELRA will be posted at 2024 Biological License Application Approvals. Efficacy was evaluated in SPEARHEAD-1, Cohort 1, a multicenter, single-arm, open-label clinical trial that enrolled HLA-A*02:01-03 and 06 allele positive patients with inoperable or metastatic synovial sarcoma who had received prior systemic therapy with either doxorubicin and/or ifosfamide and whose tumor expressed the MAGE-A4 tumor antigen. Patients received lymphodepleting chemotherapy with fludarabine and cyclophosphamide. Fifty-two patients with synovial sarcoma were enrolled and underwent leukapheresis, eight of whom did not receive afamitresgene autoleucel due to death (n=3), loss of eligibility prior to lymphodepleting chemotherapy (n=3), withdrawal by patient (n=1), and investigator decision (n=1). Forty-five patients received lymphodepletion and one patient withdrew consent before treatment, for a total of 44 patients who received a single infusion of afamitresgene autoleucel. The main efficacy outcome measure was overall response rate (ORR) according to RECIST v1.1 evaluated by independent review, supported by duration of response (DOR). ORR was 43.2% (95% Confidence Interval [CI]: 28.4, 59.0). The median time to response was 4.9 weeks (95% CI: 4.4 weeks, 8 weeks). The median DOR was 6 months (95% CI: 4.6, not reached). Among patients who were responsive to the treatment, 45.6% and 39.0% had a duration of response greater than or equal to 6 months and 12 months, respectively. The prescribing information includes a Boxed Warning for serious or fatal cytokine release syndrome (CRS), which may be severe or life-threatening. The most common nonlaboratory adverse reactions (≥ 20%) were cytokine release syndrome, nausea, vomiting, fatigue, infections, pyrexia, constipation, dyspnea, abdominal pain, non-cardiac chest pain, decreased appetite, tachycardia, back pain, hypotension, diarrhea, and edema. The most common grade 3 or 4 laboratory abnormalities (≥ 20%) were lymphocyte count decreased, neutrophil count decreased, white cell blood count decreased, red blood cell decreased, and platelet count decreased. The recommended afamitresgene autoleucel dose is between 2.68 x 109 to 10 x 109 MAGE-A4 T cell receptor (TCR) positive T cells, administered in one or more infusion bags. Do not use a leukodepleting filter or prophylactic systemic corticosteroids. This application is approved under the accelerated approval pathway. To verify the clinical benefit of afamitresgene autoleucel, the FDA and the sponsor agreed upon a postmarketing requirement for an ongoing study in adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are HLA-A*02:01P, -A*02:02P, -A*02:03P, or -A*02:06P positive and whose tumor expresses the MAGE-A4 antigen. This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This application was granted Regenerative Medicine Advanced Therapy, priority review, and orphan drug designation. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics. Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088. For assistance with single-patient INDs for investigational oncology products regulated by the Center for Biologics Evaluation and Research, healthcare professionals may email OTPRPMS@fda.hhs.gov. Follow the Oncology Center of Excellence on X: @FDAOncologyExternal Link Disclaimer. Content current as of: 08/02/2024 Regulated Product(s) Drugs 08/02/2024 Drugs Resources for Information | Approved Drugs Oncology (Cancer)/Hematologic Malignancies Approval Notifications Ongoing | Cancer Accelerated Approvals Verified Clinical Benefit | Cancer Accelerated Approvals Withdrawn | Cancer Accelerated Approvals Other | Cancer Accelerated Approvals Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) Short Description Oncology (Cancer)/Hematologic Malignancies Approval Notifications Ongoing | Cancer Accelerated Approvals Verified Clinical Benefit | Cancer Accelerated Approvals Withdrawn | Cancer Accelerated Approvals Other | Cancer Accelerated Approvals Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) Short Description

Clinical ResultAccelerated ApprovalImmunotherapyDrug ApprovalPriority Review

100 Deals associated with Ifosamide

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KEGG	Wiki	ATC	Drug Bank
D00343	Ifosamide	L01AA06	DB01181

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Bone Tissue Neoplasms	Japan	Shionogi & Co., Ltd.	14 Feb 2005
Childhood Malignant Solid Neoplasm	Japan	Shionogi & Co., Ltd.	14 Feb 2005
Gonadal Tissue Neoplasms	Japan	Shionogi & Co., Ltd.	14 Dec 2004
Hemorrhagic cystitis	United States	Baxter Healthcare Corp.	14 Aug 1987
Osteosarcoma	Japan	Shionogi & Co., Ltd.	16 Apr 1985
Prostatic Cancer	Japan	Shionogi & Co., Ltd.	16 Apr 1985
Small Cell Lung Cancer	Japan	Shionogi & Co., Ltd.	16 Apr 1985
Uterine Cervical Cancer	Japan	Shionogi & Co., Ltd.	16 Apr 1985
Breast Cancer	France	Baxter International, Inc.	01 Jan 1976
Lung Cancer	France	Baxter International, Inc.	01 Jan 1976
Lymphoma	France	Baxter International, Inc.	01 Jan 1976
Ovarian Cancer	France	Baxter International, Inc.	01 Jan 1976
Sarcoma	France	Baxter International, Inc.	01 Jan 1976
Testicular Neoplasms	France	Baxter International, Inc.	01 Jan 1976

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Refractory Osteosarcoma	Phase 2	China	Jiangsu Hengrui Pharmaceuticals Co., Ltd.	01 Mar 2022
Toxicity	Phase 2	China	Jiangsu Hengrui Pharmaceuticals Co., Ltd.	01 Mar 2022
Chondrosarcoma	Preclinical	France	Atlanthera SASU	27 Jul 2018
Ewing Sarcoma	Preclinical	France	Atlanthera SASU	14 Jul 2018

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05364424 (GO43693, ASH2024) Manual	Phase 1	Diffuse Large B-Cell Lymphoma	41	Glofitamab inIfosfamideon CarboplatinEtoposide	(vvznbysila) = speuoymthg ivxdxfnqiq (xuxmtvatzd, 60.0 - 90.7) View more	Positive	09 Dec 2024
NCT04154189 (OLIE, Pubmed \| JAMA Oncol)	Phase 2	Osteosarcoma, Recurrent Second line	81	Lenvatinib + Ifosfamide and Etoposide	zhbkesqzjb(jnnopubjfw) = mlqqwzxwiu guwpcbovbb (syrxqvpwpz, 59.3 - 86.9) View more	Negative	01 Dec 2024
				Ifosfamide and Etoposide	zhbkesqzjb(jnnopubjfw) = jajpsxzyzz guwpcbovbb (syrxqvpwpz, 47.7 - 79.2) View more
NCT03016871 (NICE, CTgov)	Phase 2	Refractory Hodgkin Lymphoma \| Recurrent Hodgkin Lymphoma	78	Laboratory Biomarker Analysis+Nivolumab+Etoposide+Carboplatin+Ifosfamide (Cohort A (Nivolumab, Etoposide, Ifosfamide, Carboplatin))	snhfrcasiu(lbbjvytgdf) = ievmbqxcsl cakdmbinoy (ffyeojejri, fmsbxesewz - hzqpghdfxb) View more	-	09 Oct 2024
				Laboratory Biomarker Analysis+Nivolumab+Etoposide+Carboplatin+Ifosfamide (Cohort B (Nivolumab, Etoposide, Ifosfamide, Carboplatin))	snhfrcasiu(lbbjvytgdf) = xzcyihtlss cakdmbinoy (ffyeojejri, agbqslofml - hhxuwepeoc) View more
ESMO2024 Manual	Phase 2	Nonseminomatous Germ Cell Tumor	34	Paclitaxelnifosfamidecisplatin	(fxlpgnlmul) = ctrjzsjtpo oudwwwwuvc (cocttpzbwg ) View more	Negative	15 Sep 2024
NCT04665765 (CTgov)	Phase 2	Primary mediastinal large B-cell lymphoma refractory \| Primary mediastinal large B-cell lymphoma recurrent \| Diffuse large B-cell lymphoma refractory \| Recurrent Non-Hodgkin Lymphoma \| Refractory Transformed Indolent B-Cell Non-Hodgkin Lymphoma \| Diffuse large B-cell lymphoma recurrent	41	Etoposide+Polatuzumab Vedotin+carboplatin+Ifosfamide+Rituximab	mskkeiifaq(dmkjajliqw) = dtlfzhwvhm bywebeuhnr (niuwypzfvu, zvzpgntobo - tgpsdznhep) View more	-	26 Aug 2024
NCT00936936 (CTgov)	Phase 2	Testicular Neoplasms \| Germ Cell and Embryonal Neoplasms	64	Bevacizumab (Cohort 1: HD GeM-DMC+ ICE + Bevacizumab for Refractory GCT)	(dhouodctwp) = envdycawbx jqalmwkqey (jtepexovgm, umidarrdob - odvwkvfpax) View more	-	26 Aug 2024
				Mesna+Etoposide+Carboplatin+Melphalan+Ifosfamide+Gemcitabine+Docetaxel (Cohort 2: HD GeM-DMC+ ICE for Refractory GCT)	(dhouodctwp) = ideeyoiegi jqalmwkqey (jtepexovgm, ekrbkhuhmv - evwjzkebbh) View more
NCT02375204 (TIGER, Pubmed) Manual	Phase 2	Germ Cell and Embryonal Neoplasms Second line	104	Paclitaxel, IIfosfamide anCisplatinin (TIP)	(hluwhlepqx) = kpkzmcfrpu sovlfypgtv (mhuxksbplg, 59 - 77) View more	Positive	19 Jul 2024
				Paclitaxel + Ifosfamide + Cisplatin (patients had favorable risk factors)	(hluwhlepqx) = mhnsipkwoo sovlfypgtv (mhuxksbplg, 61 - 80) View more
NCT02628405 (CTgov)	Phase 1/2	Primary mediastinal large B-cell lymphoma refractory \| Primary mediastinal large B-cell lymphoma recurrent \| Diffuse large B-cell lymphoma refractory \| Recurrent Non-Hodgkin Lymphoma \| B-cell lymphoma refractory \| Diffuse large B-cell lymphoma recurrent \| B-cell lymphoma recurrent	30	Laboratory Biomarker Analysis+Lenalidomide+Etoposide+Carboplatin+Ifosfamide+Rituximab	(dawpcfedcd) = dfgmhnffqd avruusword (zmfbboxerx, drvvgwfpwx - ncvsxjrblt) View more	-	01 Jul 2024
NCT04947501 (N9, ASCO2024) Manual	Early Phase 1	High Risk Neuroblastoma	15	cyclophosphamidehostopotecanopovincristineistifosfamidecarboplatinetoposide	(cnwejghxyh) = uitatoridj dilvgzlpfw (okfomghrqp ) View more	Positive	24 May 2024
				cyclophosphamideplatopotecansidvincristineifosfamidecarboplatinetoposide	(zyqubfwvhk) = bndxqvviqw pqrkpddfir (yvcvweicjf ) View more
ISN WCN2024	Not Applicable	Diabetes Insipidus \| Acidosis, Renal Tubular	-	Ifosfamide 3g/m2	mhtjbtlvyu(fycpkpkpvf) = presented after the first cycle of chemotherapy cqjinpmesd (tpyolbmptz ) View more	-	01 Apr 2024

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