A First-in-human, Open-label, Dose Escalation, Phase I Clinical Trial to Evaluate the Safety, Tolerability and Preliminary Clinical Efficacy of M3T01 Monotherapy and in Combination With Pembrolizumab and Other Systemic Therapies in Patients With Advanced Solid Tumors

Phase 1 first-in-human, open-label, dose-escalation (3 + 3), dose-expansion clinical trial to evaluate the safety, tolerability and preliminary clinical efficacy of M3T01 (fully human IgG4/kappa monoclonal antibody targeting FasL) in subjects with metastatic or unresectable solid tumors.

Start Date01 Feb 2025

Sponsor / Collaborator

Providence Health & Services

NCT06245356 / Not yet recruitingPhase 2IIT

TRIFLUOX-DP: Safety of Trifluridine/Tipiracil as Replacement of Fluoropyrimidines (5-fluorouracil and Capecitabine) Based Chemotherapy as First Line Metastatic Colorectal or Gastroesophageal Cancer Regimens in Patients With Dihydropyrimidine Dehydrogenase Deficiency: a Phase II Trial

The goal of this clinical trial is to test the safety of the trifluridine/tipiracil as replacement of fluoropyrimidines based chemotherapy as first line metastatic colorectal or gastroesophageal cancer regimens in patients with dihydropyrimidine dehydrogenase (DPD) deficiency.
The main questions it aims to answer are:
* Is this alternative chemotherapy option a better option in term of safety for this type of patients?
* Does the combination of treatments improves the overall safety?
* Does the combination of treatments improves the progression-free survival, overall survival, objective response rate and disease control rate?
* Does the combination of treatment have an effect on quality of life?
Participants will:
* Receive the trifluridine/tipiracil with oxaliplatin every 14 days, associated with:
* Panitumumab or bevacizumab for colorectal adenocarcinomas
* Nivolumab or trastuzumab for gastroesophageal adenocarcinomas.
* Have a CT-Scan every 2 months until disease progression
* Complete Health-related quality of life questionnaire every 2 months for a maximum of 6 months
* Participate to the optional translational research: Blood samples fo DPYD genotyping and pharmacokinetic analysis

Start Date31 Jan 2025

Sponsor / Collaborator

UNICANCER

[+1]

NCT05314998 / Not yet recruitingPhase 3IIT

An Open Labelled Phase III Adjuvant Trial of Disease-free Survival in Patients With Resected Pancreatic Ductal Adenocarcinoma Randomized to Allocation of Oxaliplatin- or Gemcitabine-based Chemotherapy by Standard Clinical Criteria or by a Transcriptomic Treatment Specific Stratification Signature

This is a multicentre open labelled phase III adjuvant trial of disease-free survival in patients with resected pancreatic ductal adenocarcinoma randomized to allocation of oxaliplatin- or gemcitabine-based chemotherapy by standard clinical criteria (control arm) or by a transcriptomic treatment specific stratification signature or TSS (test arm).

Start Date15 Jan 2025

Sponsor / Collaborator

Heidelberg University, U.S.

[+3]

100 Clinical Results associated with Oxaliplatin

100 Translational Medicine associated with Oxaliplatin

100 Patents (Medical) associated with Oxaliplatin

14,149

Literatures (Medical) associated with Oxaliplatin

01 Dec 2025·Journal of Gastrointestinal Cancer

Third- or Further-Line Treatment in Patients with MSS Type Metastatic Colorectal Cancer

Article

Author: Gou, Miaomiao ; Qian, Niansong ; Dai, Guanghai ; Zhang, Yong ; Wang, Zhikuan

BACKGROUND:

The survival benefit from later-line treatment for patients with metastatic colorectal cancer (mCRC) remains disappointing. Here, in a real-world study, we were aimed to evaluate which choice will affect the survival of mCRC patients after standard treatment in Chinese patients.

METHODS:

A total of 129 patients with refractory mCRC were involved in the study. They received targeted monotherapy or combined with chemo-agents or PD-1 inhibitor before death. Overall survival (OS) and progression-free survival (PFS) were reviewed and evaluated from clinical features and treatment options.

RESULTS:

Among the 129 patients, the median age was 56 years (25-81). The mOS from third-line was 12.5 months. OS of patients who treated with chemo plus targeted therapy group in third-line was shown to be superior to pd-1 inhibitor in combination with antiangiogenic agents or antiangiogenic monotherapy group (15.6 m vs. 10.5 m vs. 8.4 m, p < 0.05). Patients had received triplet-drugs (bevacizumab plus low-dose irinotecan and oxaliplatin) and had prolonged survival compared to those had not (21.3 m vs 10.3 m, p = 0.004). OS between patients who had immunotherapy history or not was not significantly different (p > 0.05). The mPFS was 3.5 months in patients who had administered with antiangiogenic targeted agents plus anti-pd-1 and 4.7 months in chemo plus targeted therapy group and 2.2 months in the other group. In the triplet drugs group, preliminary results showed that ORR was 13.3% and DCR was 80%. The median PFS was 5.1 m, and the median OS was 10.6 m.

CONCLUSIONS:

Triplet drugs resulted in significantly longer overall survival, and immunotherapy may have limited benefit in MSS type CRC patients.

01 Feb 2025·NEUROPHARMACOLOGY

Humanin attenuates metabolic, toxic, and traumatic neuropathic pain in mice by protecting against oxidative stress and increasing inflammatory cytokine

Article

Author: Hekim, Munevver Gizem ; Ayar, Ahmet ; Kelestemur, Muhammed Mirac ; Canpolat, Sinan ; Ozcan, Mete ; Bilgin, Batuhan ; Ozcan, Sibel ; Bulut, Ferah ; Adam, Muhammed

Neuropathic pain is associated with diverse etiologies, including sciatica, diabetes, and the use of chemotherapeutic agents. Despite the varied origins, mitochondrial dysfunction, oxidative stress, and inflammatory cytokines are recognized as key contributing factors in both the initiation and maintenance of neuropathic pain. The effects of the mitochondrial-derived peptide humanin on neuropathic pain, however, remain unclear, despite its demonstrated influence on these mechanisms in numerous disease models. This study aimed to evaluate the effects of humanin on pain behavior in murine models of metabolic (streptozotocin/STZ), toxic (oxaliplatin/OXA), traumatic (sciatic nerve cuffing/cuff), and neuropathic pain. A secondary objective was to assess whether humanin modulates oxidative damage and inflammatory cytokine levels in these neuropathic pain models. Humanin (4 mg/kg) was administered intraperitoneally (i.p.) to BALB/c male mice with induced neuropathic pain over a period of 15 days, with pain thresholds assessed using hot plate, cold plate, and Von Frey tests. Serum levels of antioxidant enzymes, oxidative stress markers, and inflammatory/anti-inflammatory cytokines were measured via enzyme-linked immunosorbent assay (ELISA). In neuropathic pain-induced mice, humanin administration resulted in a statistically significant increase in pain threshold values in the STZ + Humanin, OXA + Humanin, and cuff + Humanin groups compared to their respective control groups (P < 0.05) over 15 days. Furthermore, humanin treatment significantly elevated antioxidant enzyme levels and anti-inflammatory cytokine concentrations, while reducing oxidative stress markers and pro-inflammatory cytokine levels compared to control groups (P < 0.01). These findings suggest that humanin exhibits therapeutic potential in the treatment of neuropathic pain induced by STZ, OXA, and cuff models. The ability of humanin to mitigate neuropathic pain through the suppression of oxidative stress and inflammatory cytokines indicates its promise as a novel therapeutic strategy.

01 Feb 2025·Clinical Nutrition ESPEN

Skeletal muscle is independently associated with grade 3–4 toxicity in advanced stage pancreatic ductal adenocarcinoma patients receiving chemotherapy

Article

Author: Coolsen, Mariëlle M.E. ; Damink, Steven W.M. Olde ; Van Dam, Ronald M. ; Volmer, Leroy ; Brecheisen, Ralph ; Aberle, Merel R ; Aberle, Merel R. ; Rensen, Sander S. ; Wenmaekers, Gilles ; Van Dam, Ronald M ; van Dijk, David ; de Vos-Geelen, Judith ; Damink, Steven W M Olde ; Wee, Leonard ; Coolsen, Mariëlle M E ; Rensen, Sander S

BACKGROUND:

Patients with advanced-stage pancreatic ductal adenocarcinoma (PDAC) are regularly treated with FOLFIRINOX, a chemotherapy regimen based on 5-fluorouracil, irinotecan and oxaliplatin, which is associated with high toxicity. Dosing of FOLFIRINOX is based on body surface area, risking under- or overdosing caused by altered pharmacokinetics due to interindividual differences in body composition. This study aimed to investigate the relationship between body composition and treatment toxicity in advanced stage PDAC patients treated with FOLFIRINOX.

METHODS:

Data from patients treated at the Maastricht University Medical Centre + between 2012 and 2020 were collected retrospectively (n = 65). Skeletal muscle-, visceral adipose tissue, subcutaneous adipose tissue-, (SM-Index, VAT-Index, SAT-Index resp.) and Skeletal Muscle Radiation Attenuation (SM-RA) were calculated after segmentation of computed tomography (CT) images at the third lumbar level using a validated deep learning method. Lean body mass (LBM) was estimated using SM-Index. Toxicities were scored and grade 3-4 adverse events were considered dose-limiting toxicities (DLTs).

RESULTS:

Sixty-seven DLTs were reported during the median follow-up of 51.4 (95%CI 39.2-63.7) weeks. Patients who experienced at least one DLT had significantly higher dose intensity per LBM for all separate cytotoxics of FOLFIRINOX. Independent prognostic factors for the number of DLTs per cycle were: sarcopenia (β = 0.292; 95%CI 0.013 to 0.065; p = 0.013), SM-Index change (% per 30 days, β = -0.045; 95%CI -0.079 to -0.011; p = 0.011), VAT-Index change (% per 30 days, β = -0.006; 95%CI -0.012 to 0.000; p = 0.040) between diagnosis and the first follow-up CT scan, and cumulative relative dose intensity >80 % (β = -0.315; 95 % CI -0.543 to -0.087; p = 0.008).

CONCLUSION:

Sarcopenia and early muscle and fat wasting during FOLFIRINOX treatment were associated with treatment-related toxicity, warranting exploration of body composition guided personalized dosing of chemotherapeutics to limit DLTs.

459

News (Medical) associated with Oxaliplatin

11 Dec 2024

·www.globenewswire.com

Five-year results confirm Roche’s Polivy combination therapy as new standard of care for previously untreated aggressive lymphoma

Exploratory long-term follow-up analysis of the phase III POLARIX study indicated a positive trend in overall survival in favour of Polivy in combination with R-CHP for people with first-line diffuse large B-cell lymphoma (DLBCL)1 Patients treated with Polivy in combination with R-CHP required fewer subsequent treatments, potentially reducing burdens on patients and healthcare systems1 These encouraging five-year results continue to highlight the potential of this Polivy combination to improve outcomes in first-line DLBCL, an area that previously had little advancement in nearly two decades 8 December 2024 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today data from a five-year follow-up of the pivotal phase III POLARIX study evaluating Polivy® (polatuzumab vedotin) in combination with MabThera®/Rituxan® (rituximab), cyclophosphamide, doxorubicin and prednisone (R-CHP) in people with untreated diffuse large B-cell lymphoma (DLBCL). Data were presented in an oral session at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, 7-10 December 2024 in San Diego, US. This latest analysis conducted after a median follow-up of 60.9 months, includes descriptive data on primary and secondary endpoints, as well as safety results.1 “POLARIX was the first trial to elevate treatment standards for frontline diffuse large B-cell lymphoma in 20 years and we are additionally encouraged by the five-year follow-up results,” said Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development. “More than 38,000 people worldwide have been treated with Polivy in combination with R-CHP and these data continue to underscore its potential to improve outcomes for people diagnosed with this aggressive lymphoma.” Follow-up exploratory analysis after five-years indicated a positive trend in overall survival (OS) in the intent-to-treat (ITT) population in favour of Polivy in combination with R-CHP compared to MabThera/Rituxan plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). Results showed a trend in reduction in the risk of death (HR 0.85; 95% CI: 0.63–1.15) for people with previously untreated DLBCL with the Polivy combination, an improvement on the three-year follow-up data (HR 0.94; 95% CI: 0.67–1.33). The five-year analysis of POLARIX indicates that the full difference in OS between treatment arms has yet to be observed and an additional two years of follow-up will continue.1 “Diffuse large B-cell lymphoma is a notoriously challenging cancer to treat, however, Polivy in combination with R-CHP has shown to be a critical advance for patients by helping to reduce relapse and disease progression,” said Gilles Salles, MD, PhD, Chief of Lymphoma Service, Division of Hematological Malignancies, Memorial Sloan Kettering Cancer Center, US. “The survival trend seen in this follow-up analysis reinforces the potential impact of frontline treatment with Polivy in combination with R-CHP and its role as a standard of care therapy.” In addition to the positive trend in OS, an observational analysis suggested nearly 25% fewer follow-up treatments such as radiation, systemic chemotherapy and CAR-T cell therapy were needed in patients receiving Polivy in combination with R-CHP compared to those treated with R-CHOP (38.3% vs 61.7%).1 Based on findings from a previous economic analysis which found that total healthcare costs increased with each additional line of treatment in relapsed or refractory DLBCL, a reduction in the number of subsequent therapies could potentially alleviate some of the burdens associated with relapse and disease progression.2 At five years of follow-up, benefits in progression-free survival and disease-free survival with Polivy in combination with R-CHP were maintained, consistent with the three-year follow-up data, reinforcing the potential of Polivy in combination with R-CHP to provide durable and lasting remissions. The latest follow-up data also showed a numerical reduction in death related to patients’ lymphoma in those treated with Polivy in combination with R-CHP compared to those treated with R-CHOP (9.0% vs 11.4%). The safety profile remains consistent with the known profiles of the individual study medicines with no new safety signals observed, reinforcing the positive benefit-risk profile of this Polivy combination.1 Results from an expanded cohort of 1,000 patients including global and Chinese patients demonstrated comparability to the global ITT population.1 Polivy in combination with R-CHP is currently approved for the treatment of first-line (1L) DLBCL in more than 90 countries worldwide including the US, countries throughout the EU, the UK, Japan, Canada and China. Roche continues to work with health authorities around the world to bring this treatment regimen to even more patients. Roche aims to offer various treatment options for DLBCL that meet the diverse needs of patients and healthcare systems. In an effort to elevate treatment standards even further, Roche is exploring Polivy in combination with other molecules including its bispecific antibodies. Studies include the phase III SUNMO trial evaluating the efficacy and safety of subcutaneously administered Lunsumio® (mosunetuzumab) in combination with intravenous (IV) Polivy versus IV MabThera/Rituxan plus gemcitabine and oxaliplatin (R-GemOx) in second-line or later DLBCL, and the phase III SKYGLO trial investigating the efficacy of Polivy in combination with R-CHP and Columvi® (glofitamab) versus Polivy in combination with R-CHP in 1L DLBCL. POLARIX [NCT03274492] is an international phase III, randomised, double-blind, placebo-controlled study evaluating the efficacy, safety and pharmacokinetics of Polivy® (polatuzumab vedotin) plus MabThera®/Rituxan® (rituximab), cyclophosphamide, doxorubicin, and prednisone (R-CHP) versus rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) in people with previously untreated diffuse large B-cell lymphoma (DLBCL). Eight-hundred and seventy-nine patients were randomised 1:1 to receive either Polivy plus R-CHP plus a vincristine placebo for six cycles, followed by MabThera/Rituxan for two cycles; or R-CHOP plus a Polivy placebo for six cycles, followed by two cycles of MabThera/Rituxan. The primary outcome measure is progression-free survival (PFS) as assessed by the investigator using the Lugano Response Criteria for malignant lymphoma. PFS is a clinically meaningful disease-related outcome for patients with previously untreated DLBCL as it represents the goal of first-line therapy: decreasing the risk of disease worsening. Overall survival is a secondary endpoint in the POLARIX study. DLBCL is the most common form of non-Hodgkin lymphoma (NHL), accounting for about one in three cases of NHL.3 DLBCL is an aggressive (fast-growing) type of NHL. While it is generally responsive to treatment in the frontline, as many as 40% of people will relapse or have refractory disease, at which time salvage therapy options are limited and survival is short. 4,5 Improving treatments earlier in the course of the disease and providing much needed alternative options could help to improve long-term outcomes. Approximately 160,000 people worldwide are estimated to be diagnosed with DLBCL each year.1,6 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 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 minimise the effects on normal cells. Polivy is being developed by Roche using Pfizer ADC technology and is currently being investigated for the treatment of several types of NHL. Roche has been developing medicines for people with malignant and non-malignant blood diseases for more than 25 years; our experience and knowledge in this therapeutic area runs deep. Today, we are investing more than ever in our effort to bring innovative treatment options to patients across a wide range of haematologic diseases. Our approved medicines include MabThera/Rituxan, Gazyva®/Gazyvaro® (obinutuzumab), Polivy, Venclexta®/Venclyxto® (venetoclax) in collaboration with AbbVie, Hemlibra® (emicizumab), PiaSky® (crovalimab), Lunsumio® (mosunetuzumab) and Columvi® (glofitamab). Our pipeline of investigational haematology medicines includes T-cell engaging bispecific antibody cevostamab, targeting both FcRH5 and CD3 and Tecentriq® (atezolizumab). Our scientific expertise, combined with the breadth of our portfolio and pipeline, also provides a unique opportunity to develop combination regimens that aim to improve the lives of patients even further. Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice. For over 125 years, sustainability has been an integral part of Roche’s business. As a science-driven company, our greatest contribution to society is developing innovative medicines and diagnostics that help people live healthier lives. Roche is committed to the Science Based Targets initiative and the Sustainable Markets Initiative to achieve net zero by 2045. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. References [1] Gilles S, et al. 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. Presented at: ASH Annual Meeting and Exposition; 2024 Dec 7-10; San Diego, CA, USA. Abstract #469. [2] Gatwood J, et al. Total cost of care in Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL). Presented at: ASH Annual Meeting and Exposition; 2022, Dec 10-13. Abstract #3527 [3] Cancer.Net. Lymphoma - Non-Hodgkin: Subtypes. [Internet; cited December 2024]. Available from: https://www.cancer.net/cancer-types/lymphoma-non-hodgkin/subtypes [4] Sehn LH, et al. Diffuse Large B-Cell Lymphoma. N Engl J Med. 2021;384(9):842-858. [5] Maurer MJ, et al. Event-free survival at 24 months is a robust end point for disease-related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy. J Clin Oncol. 2014;32:1066-73. [6] World Health Organization. Numbers derived from GLOBOCAN 2022. Non-Hodgkin Lymphoma Factsheet [Internet; cited December 2024]. Available from: https://gco.iarc.who.int/media/globocan/factsheets/cancers/34-non-hodgkin-lymphoma-fact-sheet.pd. The content above comes from the network. if any infringement, please contact us to modify.

Clinical ResultASHDrug Approval

06 Dec 2024

·www.prnewswire.com

Charles R. Scheper, Chairman of Bexion Pharmaceuticals Board, Named Great Living Cincinnatian

COVINGTON, Ky., Dec. 6, 2024 /PRNewswire/ -- Bexion Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company developing a novel class of biologic therapy to treat solid tumor cancers and chemotherapy-induced peripheral neuropathy (CIPN), today announced that its Chairman of the Board, Charles R. Scheper, has been named a Great Living Cincinnatian by The Cincinnati Regional Chamber. Being named a Great Living Cincinnatian is regarded as the preeminent honor in the Cincinnati community. According to The Cincinnati Regional Chamber, Great Living Cincinnatians are recognized by the Cincinnati Regional Chamber for service to the community; business and civic attainment on a local, state, national or international level; leadership; awareness of the needs of others; and distinctive accomplishments that have brought favorable attention to their community, institution, or organization. Mr. Charles "Chuck" Scheper joined Bexion as Chairman of the Board in 2010. He was the Chief Operating Officer at Great American Financial Resources, a $20 billion life and annuity company until his retirement in 2010. Prior to that position, Mr. Scheper was president and chief executive officer of Manhattan National Life Insurance Company and president of Pioneer Financial Services. Chuck is a cancer survivor and his journey to wellness led him to become active in various causes related to cancer, including Cancer Support Community, where he has served as the National Board Chairperson and board member. Currently, he is also the Chair of Catalytic Development Funding Corp of Northern Kentucky and Covington Economic Development Authority. "We are incredibly proud to celebrate our Chairman of the Board, Chuck Scheper, as a Great Living Cincinnatian," said Jim Beach, Bexion's Chief Executive Officer. "This recognition reflects his outstanding leadership and significant impact on our community. Chuck embodies the values we strive for at Bexion and inspires us to continue making a difference in people's lives." More information about the award and upcoming award ceremony in 2025 is available here. About BXQ-350 Bexion's lead drug candidate is BXQ-350, a first-in-class biologic containing the multifunctional sphingolipid activator protein, Saposin C, and a phospholipid. Multiple Phase 1 clinical trials in adult and pediatric patients have demonstrated a robust safety profile for BXQ-350 with evidence of single agent activity across multiple solid tumor types. Additionally, other clinical and non-clinical data suggest BXQ-350 has activity in chemotherapy-induced peripheral neuropathy, an area of high unmet medical need in patients treated with oxaliplatin and other chemotoxic agents. About Bexion Pharmaceuticals Bexion Pharmaceuticals, a clinical-stage biopharmaceutical company, is developing a new generation of biologic therapy to treat solid tumor cancers and chemotherapy-induced peripheral neuropathy (CIPN) with potential portfolio expansion opportunities in other cancers and broader neuropathic pain indications. Bexion has generated data in multiple classes of solid tumors, including colorectal cancer, high-grade gliomas, and pediatric brain tumors. The Company has completed enrollment in the open label portion of its Phase 1b/2 study evaluating BXQ-350 in combination with the standard of care. The Company is now planning to proceed to the randomized, double-blind, placebo-controlled portion of the study. The Company has also completed enrollment in a proof-of-concept trial for the treatment of CIPN. About the Cincinnati Regional Chamber The Cincinnati Regional Chamber is the premier business and civic organization dedicated to growing the vibrancy and economic prosperity of the Cincinnati region. To achieve its vision that Cincinnati is a growing, thriving region where everyone belongs, the Chamber seeks to grow their economy, grow their population, and grow their cultural vibrancy — with the foundation of a strong business community — to foster a welcoming environment for all. The Chamber's membership offerings, signature leadership programs, government and regional advocacy efforts, community events such as BLINK and Oktoberfest as well as key partnerships with organizations like Cincinnati Experience, Cincinnati Compass, Cincinnati Minority Business Accelerator, and the Workforce Innovation Center lead the way in making that vision a reality. For more information, visit . Investor Contact: William Windham Solebury Strategic Communications 646-378-2946 [email protected] Media Contact: Joyce LaViscount Bexion Pharmaceuticals 859-446-7386 [email protected] SOURCE Bexion Pharmaceuticals, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 1Executive Change

05 Dec 2024

·www.globenewswire.com

Medicenna Provides Clinical Update and Announces First Complete Responder in MDNA11 and KEYTRUDA® (pembrolizumab) Combination Dose Escalation Arm of the ABILITY-1 Study

70-year-old patient with advanced chemo-refractory anal cancer achieves complete response (CR) in 8 weeks when treated with MDNA11 in combination with Merck’s (known as MSD outside of the US and Canada) anti-PD-1 therapy, KEYTRUDA® (pembrolizumab) Complete regression of all tumors in two CPI-resistant patients in monotherapy arms continue to show durability with a patient with melanoma remaining tumor free at week 63 while a patient with pancreatic cancer remains off all anti-cancer therapy for 11 months after completing the study A patient with advanced MSS colorectal cancer with a previously announced partial response (PR) continues treatment in the combination escalation arm as of week 32 with a confirmed PR Both objective responses (1 CR and 1PR) among evaluable patients in the combination dose escalation arm (N=9) are in tumor types with high unmet need and where checkpoint inhibitors (CPI) have not been approved The ABILITY-1 study is showing promising disease control rates (DCR = CR+PR+SD) of 55% (1 CR, 4 PRs, and 6 SDs) and 78% (1 CR, 1 PR and 5 SDs) in the monotherapy and combination arms, respectfully Additional monotherapy and combination clinical data from the ABILITY-1 study will be presented at medical conferences in Q1 and Q2 of 2025 TORONTO and HOUSTON, Dec. 05, 2024 (GLOBE NEWSWIRE) -- Medicenna Therapeutics Corp. (“Medicenna” or the “Company”) (TSX: MDNA, OTCQX: MDNAF), a clinical-stage immunotherapy company focused on the development of Superkines, announced that updated clinical data from the ongoing Phase 1/2 ABILITY-1 study were presented today at the 2024 Immunotherapy Bridge held in Naples, Italy. The oral presentation by Dr Arash Yavari, MB BS, DPhil, included new data highlighting the first complete response (CR) in the combination dose escalation phase of the study in a 70-year-old patient with advanced anal squamous cell carcinoma (anal SCC), in addition to follow up safety and efficacy results from the monotherapy and combination arms of the ABILITY-1 study. The anal SCC patient previously progressed on two prior lines of treatment comprising of chemotherapy combination and chemo-radiation treatments. The patient achieved a 100% reduction of all measurable target and non-target lesions by Week 8, highlighting MDNA11’s potential to enhance checkpoint inhibitor efficacy in advanced solid tumor types traditionally considered less sensitive to immunotherapy. “These remarkable results from our monotherapy and early data from the combination dose escalation highlights the transformative potential of MDNA11 as a combination therapy with checkpoint inhibitors like KEYTRUDA®, while demonstrating an acceptable safety profile as dose escalation continues,” said Fahar Merchant, PhD, President and CEO of Medicenna. “Achieving a complete response in a patient with anal squamous cell carcinoma, a cancer with historically low immunotherapy response rates, demonstrates MDNA11’s ability to reinvigorate the immune system and tackle difficult-to-treat tumors. We look forward to sharing additional clinical data at medical conferences in Q1 and Q2 of 2025 as we advance MDNA11 as a potent and safe immunotherapy to dramatically improve current immunotherapies and deliver life-changing outcomes for patients.” Key findings from the on-going ABILITY-1 study (data cut-off as of November 18th, 2024) include: Safety Profile MDNA11 has a favorable safety profile both as a monotherapy and in combination with KEYTRUDA®. Over 90% of treatment-related adverse events (TRAEs) were Grade 1-2 and transient, with no DLTs or new safety signals observed in combination dose escalation cohorts. MDNA11 at doses of 120 µg /kg (Q3W monotherapy; Q2W and Q3W in combination with Keytruda (400 mg Q6W) are currently being evaluated. Immunodynamics MDNA11 preferentially expands immune effector cells, including activated (CD25+) and “stemness-like” (TCF-1+) CD8+ T cells, which are critical for sustained anti-tumor responses.Robust, dose-dependent lymphocyte expansion in combination with KEYTRUDA®, sustained with repeat MDNA11 dosing. Monotherapy Tumor Response in Immune Checkpoint Inhibitor-Resistant Patients MDNA11 continues to demonstrate encouraging deep and durable single-agent anti-tumor activity among patients who progressed on prior ICI therapy: An objective response rate (ORR) of 30% in the monotherapy dose expansion arm with 3 PRs among 10 patients who had all previously failed ICI therapy and had advanced and/or metastatic melanoma, non-melanoma skin cancer or MSI-H/dMMR tumors. The ORR is 25% from a total of 20 patients when including 10 phase 2 eligible patients from the MDNA11 monotherapy dose escalation arm who received at least 60 µg/kg MDNA11 and were ICI-resistant.Overall, objective responses in ICI-resistant patients include 1 CR and 4 PRs 2 PRs among 3 MSI-H patients (ORR of 66.7%) with both responders having metastatic pancreatic ductal adenocarcinoma (PDAC).1 CR and 2 PRs among 11 patients with cutaneous melanoma (ORR of 27.3%). Complete resolution of all target and non-target lesions in two patients: 1 confirmed CR in a melanoma patient continues on treatment as of week 63.Pancreatic cancer patient (MSI-H) achieved complete resolution of target and non-target metastatic lesions in the liver including a new lesion treated with MDNA11 following a single cycle of radiation, achieved durable response for 20 months during the study and continues to remain off anti-cancer therapy for 11 months. SD in 6 patients for a disease control rate (DCR = CR+PR+SD) of 55% including 3 with duration > 6 months, yielding a clinical benefit rate of 40% (8/20). MDNA11 Combination with KEYTRUDA® Tumor Response The objective of the combination dose escalation/evaluation portion of the ABILITY-1 study is to assess the safety, pharmacokinetics and immunodynamics of MDNA11 at various doses and dosing regimens when combined with KEYTRUDA® (400mg, Q6W), and to determine the recommended dose and schedule for the combination dose expansion portion of the study. Encouraging preliminary signs of anti-tumor activity have been observed with MDNA11 in combination with KEYTRUDA® to date in dose escalation cohorts 1 (60 µg/kg Q2W MDNA11) and 2 (90 µg/kg Q2W MDNA11). Among 9 heavily pre-treated, efficacy-evaluable patients, tumor control was observed in 7 patients for a DCR of 78% including a CR in an anal squamous cell carcinoma patient and PR in a microsatellite-stable (MSS) colorectal cancer patient. CR in a 70-year-old male with anal squamous cell carcinoma Patient progressed on 2 prior lines of chemotherapy (1L capecitabine/mitomycin plus radiation therapy; 2L carboplatin/paclitaxel)CR achieved on first study evaluable imaging scan at Week 8; patient continues on combination treatment Confirmed PR in 52-year-old female with MSS colorectal cancer Patient progressed on 2 prior lines of chemotherapy (1L folinate/fluorouracil/oxaliplatin; 2L capecitabine)Continues on combination treatment as of week 32 A copy of the presentation has been posted on the “Scientific Presentations” page of Medicenna’s website. About MDNA11 MDNA11 is an intravenously administered, long-acting, ‘beta-enhanced not-alpha’ IL-2 Superkine specifically engineered to overcome the shortcomings of aldesleukin and other next generation IL-2 variants by preferentially activating immune effector cells (CD8+ T and NK cells) responsible for killing cancer cells, with minimal or no stimulation of immunosuppressive Tregs. These unique proprietary features of the IL-2 Superkine have been achieved by incorporating seven specific mutations and genetically fusing it to a recombinant human albumin scaffold to improve the pharmacokinetic (PK) profile and pharmacological activity of MDNA11 due to albumin’s natural propensity to accumulate in highly vascularized sites, in particular tumor and tumor draining lymph nodes. MDNA11 is currently being evaluated in the Phase 1/2 ABILITY-1 study as both monotherapy and in combination with KEYTRUDA®. About the ABILITY-1 Study The ABILITY-1 study (NCT05086692) is a global, multi-center, open-label study that assesses the safety, tolerability, pharmacokinetics, pharmacodynamics and anti-tumor activity of MDNA11 as monotherapy or in combination with KEYTRUDA®. In the combination dose escalation portion of the Phase 2 study, approximately 20 patients are expected to be enrolled and administered ascending doses of MDNA11 intravenously in combination with KEYTRUDA®. This portion of the study includes patients with a wide range of solid tumors with the potential for susceptibility to immune modulating therapeutics. Upon identification of an appropriate dose regimen for combination, the study will proceed to combination dose expansion. About Medicenna Therapeutics Medicenna is a clinical-stage immunotherapy company focused on developing novel, highly selective versions of IL-2, IL-4 and IL-13 Superkines and first-in-class Empowered Superkines. Medicenna’s long-acting IL-2 Superkine, MDNA11, is a next-generation IL-2 with superior affinity toward CD122 (IL-2 receptor beta) and no CD25 (IL-2 receptor alpha) binding, thereby preferentially stimulating cancer-killing effector T cells and NK cells. MDNA11 is being evaluated in the Phase 1/2 ABILITY-1 Study (NCT05086692) as a monotherapy and in combination with KEYTRUDA®. Medicenna’s IL-4 Empowered Superkine, bizaxofusp (formerly MDNA55), has been studied in 5 clinical trials enrolling over 130 patients, including a Phase 2b trial for recurrent GBM, the most common and uniformly fatal form of brain cancer. Bizaxofusp has obtained FastTrack and Orphan Drug status from the FDA and FDA/EMA, respectively. Medicenna’s early-stage high-affinity IL-2β biased IL-2/IL-15 Super-antagonists, from its MDNA209 platform, are being evaluated as potential therapies for autoimmune and graft-versus host diseases. Medicenna’s early-stage BiSKITs™ (Bifunctional SuperKine ImmunoTherapies) and the T-MASK™ (Targeted Metalloprotease Activated SuperKine) programs are designed to enhance the ability of Superkines to treat immunologically “cold” tumors. For more information, please visit www.medicenna.com, and follow us on Twitter and LinkedIn. Forward-Looking Statements This news release may contain forward-looking statements within the meaning of applicable securities laws. Forward-looking statements include, but are not limited to, express or implied statements regarding the future operations of the Company, estimates, plans, strategic ambitions, partnership activities and opportunities, objectives, expectations, opinions, forecasts, projections, guidance, outlook or other statements that are not historical facts, such as statements on the therapeutic treatment potential and safety profile of MDNA11 (both as monotherapy and in combination with KEYTRUDA®) and the timing and/or release of any additional clinical updates. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early-stage pre-clinical or clinical studies may not be indicative of full results or results from later stage or larger scale clinical studies and do not ensure regulatory approval. You should not place undue reliance on these statements, or the scientific data presented. Forward-looking statements are often identified by terms such as “will”, “may”, “should”, “anticipate”, “expect”, “believe”, “seek”, “potentially” and similar expressions. and are subject to risks and uncertainties. Forward-looking statements are based on a number of assumptions believed by the Company to be reasonable at the date of this news release. Although the Company believes that the expectations reflected in such forward-looking statements are reasonable, there can be no assurance that such statements will prove to be accurate. These statements are subject to certain risks and uncertainties and may be based on assumptions that could cause actual results and future events to differ materially from those anticipated or implied in such statements. Important factors that could cause actual results to differ materially from the Company’s expectations include the risks detailed in the latest annual information form of the Company and in other filings made by the Company with the applicable securities regulators from time to time in Canada. The reader is cautioned that assumptions used in the preparation of any forward-looking information may prove to be incorrect. Events or circumstances may cause actual results to differ materially from those predicted, as a result of numerous known and unknown risks, uncertainties, and other factors, many of which are beyond the control of the Company. The reader is cautioned not to place undue reliance on any forward-looking information. Such information, although considered reasonable by management, may prove to be incorrect and actual results may differ materially from those anticipated or implied in forward-looking statements. Forward-looking statements contained in this news release are expressly qualified by this cautionary statement. The forward-looking statements contained in this news release are made as of the date hereof and except as required by law, we do not intend and do not assume any obligation to update or revise publicly any of the included forward-looking statements. This news release contains hyperlinks to information that is not deemed to be incorporated by reference in this new release. Investor and Company Contact: Christina CameronInvestor Relationsir@medicenna.com(647) 953-0673 Daniel ScarrInvestor Relations & Business Developmentdscarr@medicenna.com(647) 220-4509

Clinical ResultImmunotherapyPhase 2Orphan DrugRadiation Therapy

100 Deals associated with Oxaliplatin

External Link

KEGG	Wiki	ATC	Drug Bank
D01790	Oxaliplatin	L01XA03	DB00526

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Small intestine carcinoma	JP	Yakult Honsha Co., Ltd.	21 Sep 2018
Stomach Cancer	JP	Yakult Honsha Co., Ltd.	20 Mar 2015
Pancreatic Cancer	JP	Yakult Honsha Co., Ltd.	20 Dec 2013
Colorectal Cancer	US	Sanofi-Aventis U.S. LLC	10 Jan 2007
Advanced Colorectal Adenocarcinoma	AU	Medis Pharma Pty Ltd.	28 Nov 2006
Colonic Cancer	US	Sanofi-Aventis U.S. LLC	09 Aug 2002
Rectal Cancer	US	Sanofi-Aventis U.S. LLC	09 Aug 2002
Neoplasms	CN	Nanjing Pharmaceutical Factory	01 Jan 2000

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diffuse Large B-Cell Lymphoma	Phase 3	US	Hoffmann-La Roche, Inc.	23 Feb 2021
Diffuse Large B-Cell Lymphoma	Phase 3	CN	Hoffmann-La Roche, Inc.	23 Feb 2021
Diffuse Large B-Cell Lymphoma	Phase 3	AU	Hoffmann-La Roche, Inc.	23 Feb 2021
Diffuse Large B-Cell Lymphoma	Phase 3	BE	Hoffmann-La Roche, Inc.	23 Feb 2021
Diffuse Large B-Cell Lymphoma	Phase 3	DK	Hoffmann-La Roche, Inc.	23 Feb 2021
Diffuse Large B-Cell Lymphoma	Phase 3	FR	Hoffmann-La Roche, Inc.	23 Feb 2021
Diffuse Large B-Cell Lymphoma	Phase 3	DE	Hoffmann-La Roche, Inc.	23 Feb 2021
Diffuse Large B-Cell Lymphoma	Phase 3	PL	Hoffmann-La Roche, Inc.	23 Feb 2021
Diffuse Large B-Cell Lymphoma	Phase 3	PR	Hoffmann-La Roche, Inc.	23 Feb 2021
Diffuse Large B-Cell Lymphoma	Phase 3	KR	Hoffmann-La Roche, Inc.	23 Feb 2021

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03217097 (MGMT-NET, Pubmed \| J Clin Oncol)	Phase 2	Neuroendocrine Tumors	105	Alkylating agents	ttomxwwhbe(jgtpdqsodl) = lddvprzteq wqsjqouwpn (zevlqtksne ) View more	Positive	25 Nov 2024
NCT03217097 (MGMT-NET, Pubmed \| J Clin Oncol)	Phase 2	Neuroendocrine Tumors	105	Oxaliplatin	ttomxwwhbe(jgtpdqsodl) = acqurpdqel wqsjqouwpn (zevlqtksne ) View more	Positive	25 Nov 2024
NCT03259035 (CCTG CO.28 \| NEO \| CO.28, CTgov)	Phase 2	Rectal Cancer	58	folinic acid+oxaliplatin+capecitabine+fluorouracil	wrkyvazkie(jkhtndagzm) = hehmppklmw jnzctriapb (jvyqthrqkz, ogvabwxsql - gufgqbvrja) View more	-	10 Oct 2024
NCT03483038 (NEO-Nal-IRI, CTgov)	Phase 2	Pancreatic adenocarcinoma	45	LEUCOVORIN CALCIUM+Liposomal Irinotecan+Oxaliplatin+Fluorouracil	sdirpjfaik(fbbzlwnrxv) = xztbkfqaxu bcztnhllzo (wkqhfwjqgs, vttjlznhze - wzagntfzfx) View more	-	23 Sep 2024
NCT03388190 (METIMMOX, ESMO2024)	Phase 2	Metastatic Microsatellite Stable Colorectal Carcinoma First line TMB \| BRAF-V600E \| CRP	34	FLOX (oxaliplatin, 5-fluorouracil, folinic acid) Q2W	mhiodqxjka(zvuobwjvsv) = grkkhrgpzo mgnelksymw (xljrkcnchz ) View more	Positive	16 Sep 2024
SOHO2024	Not Applicable	Diffuse Large B-Cell Lymphoma	-	AZA+ R-GemOx	exnutkeyof(qhsyrfuxbb) = Grades 3–4 adverse events were mainly hematological, and all toxicities were transient and reversible qbicenvfxc (nzwwtwjhuk )	-	04 Sep 2024
NCT01595321 (CTgov)	Phase 2	Pancreatic adenocarcinoma	19	Stereotactic Body Radiation+Leucovorin Calcium+irinotecan+oxaliplatin+Irinotecan hydrochloride+FLUOROURACIL (Cohort 1: SBRT and FOLFIRINOX)	ivgmclrzvo(qporfkgybn) = fqgpiyzxkb ziyovxfkhc (srxjqwbtso, gowvryorow - lwdljfxjjv) View more	-	14 Aug 2024
NCT01595321 (CTgov)	Phase 2	Pancreatic adenocarcinoma	19	Stereotactic Body Radiation (Cohort 2: SBRT and Modified FOLFIRINOX)	ivgmclrzvo(qporfkgybn) = xyparvljxa ziyovxfkhc (srxjqwbtso, ispbohlvfj - khwxbjzidt) View more	-	14 Aug 2024
NCT01515748 (PRODIGY, Pubmed)	Phase 3	Advanced gastric carcinoma Neoadjuvant \| Adjuvant	-	Neoadjuvant Docetaxel, Oxaliplatin, and S-1 Plus Surgery and Adjuvant S-1	qvwvldgxxe(atgpgeuifa) = iuskzbgnty boohbmfjtf (qtpsnszuci )	Positive	12 Jul 2024
NCT02352337 (PRODIGE 35-PANOPTIMOX \| PANOPTIMOX, CTgov)	Phase 2	Secondary malignant neoplasm of pancreas	276	Leucovorin Calcium+irinotecan+oxaliplatin+Irinotecan hydrochloride+FLUOROURACIL (FOLFIRINOX)	cotvykuzxu(pfreimwqwm) = trhzkohlwn dlabptzsbm (psnmqugycd, ofiuqiajcu - sdajcggvlo) View more	-	10 Jul 2024
NCT02352337 (PRODIGE 35-PANOPTIMOX \| PANOPTIMOX, CTgov)	Phase 2	Secondary malignant neoplasm of pancreas	276	LV+irinotecan+oxaliplatin+Irinotecan hydrochloride+FLUOROURACIL (FOLFIRINOX + LV5FU2 in Maintenance)	cotvykuzxu(pfreimwqwm) = mjyrfudmdu dlabptzsbm (psnmqugycd, migboowbqd - pekgblsfwb) View more	-	10 Jul 2024
IRCT20140903019036N3 (ESMO_GI2024) Manual	Phase 2	Esophageal Carcinoma Neoadjuvant	59	Carboplatin/Paclitaxel (CP) regimen	pvyrxaebpg(ftslmkazgl) = yoefqwnmtf tggvbjnpkw (ikxdtzadht )	Similar	20 Jun 2024
IRCT20140903019036N3 (ESMO_GI2024) Manual	Phase 2	Esophageal Carcinoma Neoadjuvant	59	Oxaliplatin/Capecitabine (XELOX) regimen	pvyrxaebpg(ftslmkazgl) = jbzqkplqoq tggvbjnpkw (ikxdtzadht )	Similar	20 Jun 2024
ESMO_GI2024	Not Applicable	Colorectal Cancer	-	Oxaliplatin (CRC patients with HSR to OXL)	tzlultfbng(tgivhkocbh) = OIIS is a rare but potentially fatal complication caused by a type II antibody-mediated hypersensitivity reaction (HSR), with different clinical presentations including autoimmune haemolytic anaemia, acute immune thrombocytopenia (AIT), Evans Syndrome (ES) and thrombotic microangiopathy (TMA) sxoctmjfmi (tozdbrswxc ) View more	-	20 Jun 2024

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