Phase Ib/II Study to Evaluate Safety and Tolerability of Neoadjuvant Nivolumab and Chemotherapy in Patients With Localized Triple-negative Breast Cancer

Prior to Amendment #7: The hypothesis of this study is that the combination of cabiralizumab and nivolumab with neoadjuvant chemotherapy will decrease tumor associated macrophages (TAMs) and increase tumor infiltrating lymphocytes (TIL) compared to neoadjuvant chemotherapy plus nivolumab in patients with early stage triple-negative breast cancer (TNBC) and improve clinical outcomes.
As of Amendment #7 IRB approved 10/13/2022: The study will no longer enroll to Arm B. Cabiralizumab will no longer be given. The hypothesis of this study is that on-treatment tumor associated macrophages (TAMs) and tumor infiltrating lymphocytes (TILs) will improve (reduced TAMs, increased TILs) following neoadjuvant nivolumab with chemotherapy.

Start Date19 Nov 2020

Sponsor / Collaborator

Washington University School of Medicine

[+1]

NCT03768531

/ WithdrawnPhase 2IIT

Safety and Tolerability Study of Combination Nivolumab and Cabiralizumab as Neoadjuvant and Adjuvant Therapy for Resectable Biliary Tract Cancer

The purposed of this research is to study the safety and clinical activity of the combination of nivolumab and cabiralizumab in people with resectable biliary tract cancers (BTC).

Start Date14 Jun 2019

Sponsor / Collaborator

The Sidney Kimmel Comprehensive Cancer Center

[+1]

NCT03927105

/ CompletedPhase 2IIT

Nivolumab and the Antagonistic CSF-1R Monoclonal Antibody Cabiralizumab (BMS-986227) in Patients With Relapsed/Refractory Peripheral T Cell Lymphoma

A multicenter trial evaluating the combination of nivolumab and the antagonistic CSF-1R monoclonal antibody cabiralizumab (BMS-986227) in patients with relapsed/refractory peripheral T cell lymphoma

Start Date25 Apr 2019

Sponsor / Collaborator

Rogel Cancer Center: University of Michigan

[+1]

100 Clinical Results associated with Cabiralizumab

100 Translational Medicine associated with Cabiralizumab

100 Patents (Medical) associated with Cabiralizumab

Literatures (Medical) associated with Cabiralizumab

01 May 2025·Journal for ImmunoTherapy of Cancer

Rationale and feasibility of a rapid integral biomarker program that informs immune-oncology clinical trials: the ADVISE trial

Article

Author: Tam, Rachel ; Luke, Jason J ; Gupta, Akshita ; Lee, George ; Reilly, Tim ; Szabo, Peter ; Yao, David ; Dutta, Santanu ; Taube, Janis ; Bao, Riyue ; Massey, Ashish ; Bever, Katherine ; Neely, Jaclyn ; Hodi, F Stephen

Background:

ADVISE (ADaptiVe biomarker trial that InformS Evolution of therapy) (NCT03335540) was a biomarker-adapted feasibility clinical trial of immunohistochemistry (IHC) to inform combination immuno-oncology (I-O) treatment.

Methods:

To inform I-O combination selection, messenger RNA expression analyses from The Cancer Genome Atlas evaluated associations between programmed death 1/programmed death ligand 1 (PD-1/PD-L1) and other I-O-associated genes. Tumor tissue blocks of melanoma, non-small cell lung cancer, renal cell carcinoma, urothelial carcinoma, squamous cell carcinoma of the head and neck, and gastroesophageal junction/gastric cancer were stained by IHC to assess expression of CD8, colony-stimulating factor 1 receptor, glucocorticoid-induced tumor necrosis factor receptor (GITR), indoleamine 2,3-dioxygenase 1, lymphocyte-activation gene 3, NKp46, forkhead box P3, and PD-L1. These results facilitated an I-O treatment selection algorithm where patient biopsy results dictated allocation into combinations of nivolumab with cabiralizumab, urelumab, linrodostat mesylate, relatlimab, BMS-986156 (anti-GITR), lirilumab, ipilimumab, or irradiation. The primary endpoint was the proportion of patients with qualified baseline tumor biopsy specimens where decision-enabling biomarker analysis was completed within 12 business days to select an I-O combination therapy.

Results:

Correlation of PD-1/L1 and I-O-associated genes varied across the spectrum of T-cell-inflamed versus non-inflamed tumors; however, tumors with low/intermediate PD-L1 expression demonstrated distinct upregulation of immune markers grouped by cell type (T cell, macrophage, etc). IHC analyses of I-O naïve tumors corroborated these findings with distinct immune target upregulation in low-to-intermediate inflamed tumors and significant associations between IHC-detected markers and T-cell inflammation score across most markers. In the clinical trial, 20/23 (87%) of eligible patients were successfully allocated and started on treatment within the 12-day window, meeting the primary endpoint. The safety profile appeared to generally align with those reported for the individual combinations from other trials. No treatment responses occurred. Most patients were allocated to the cabiralizumab treatment arm.

Conclusions:

Actualization of a patient-specific I-O combination treatment selection strategy is feasible, however, determination of de novo integral biomarker thresholds of novel I-O targets to facilitate effective treatment of PD-1-refractory cancer remains fraught. These data emphasize the difficulty of integral biomarker development for I-O in translating from immunotherapy treatment-naïve biospecimens to the selection of patients in the PD-1-refractory state.

Trial registration number:

NCT03335540.

01 Sep 2024·EUROPEAN JOURNAL OF CANCER

Safety of combined ablative radiotherapy and immune checkpoint inhibitors in three phase I trials

Article

Author: Korpics, Mark C ; Pitroda, Sean P ; Chmura, Steven J ; Katipally, Rohan R ; Patel, Jyoti D ; Bestvina, Christine M ; Juloori, Aditya ; Luke, Jason J ; Lynch, Connor

BACKGROUND:

Stereotactic body radiotherapy (SBRT) is safe and effective for treatment of extracranial metastatic disease, but its safety when combined with immune checkpoint inhibitors (ICI) has not yet been comprehensively reported. Here we report adverse events (AEs) associated with combined SBRT and ICI using prospectively-collected data on patients in three trials investigating multi-site SBRT combined with ICI.

METHODS:

Patients were included from three prospective trials of ICI (pembrolizumab; nivolumab/urelumab or nivolumab/cabiralizumab; nivolumab/ipilimumab) with SBRT to 1-4 sites. AEs were recorded prospectively using the CTCAE v4.0. Survival was analyzed using Kaplan-Meier method with a 90-day landmark. Association of patient characteristics with cumulative incidence of AEs was assessed using Fine-Gray regression.

RESULTS:

213 patients were included, with a median follow-up of 10 months. Over the follow-up period, 50 % and 27 % of patients experienced at least one grade ≥ 2 or grade ≥ 3 AE, respectively. Cumulative incidences of grade ≥ 2 and grade ≥ 3 AEs at 6 months were 47 % and 23 %, respectively. Three grade 5 AEs rated "possibly" related to treatment occurred outside the 90-day dose-limiting toxicity window. Landmarked survival analysis of patients with or without grade ≥ 3 AEs showed no significant difference in progression-free or overall survival. Dual-agent ICI was significantly associated with grade ≥ 3 AE.

CONCLUSION:

This analysis features the largest prospectively evaluated cohort of patients treated with combination ablative SBRT and ICI to date and provides context for future trial design. We conclude that multi-site SBRT and ICI can be safely co-administered when SBRT is delivered with prioritization of normal tissue constraints.

01 Oct 2023·Hematology/oncology and stem cell therapy

Updates on the Treatment of Tenosynovial Giant Cell Tumor

Review

Author: Chan, Abigail S. ; Singh, Vikas ; Katiyar, Vatsala ; Dy, Paul

Tenosynovial giant cell tumor (TGCT) is a rare inflammatory disorder affecting the joint synovium, bursae, and tendon sheaths that causes non-specific and often insidious joint discomfort. The application of systemic chemotherapy has been limited due to poor and unsustained disease responses. Surgery with or without adjuvant radiation is the primary treatment modality for TGCT. With its locally destructive nature and increased recurrence, multiple surgical interventions become necessary throughout the course of the disease, leading to disfigurement, decreased quality of life, and increased mortality. However, owing to recent evidence demonstrating the overexpression of colony-stimulating factor 1 (CSF-1) in TGCT, selective tyrosine kinase inhibitors targeting CSF-1 receptors are being developed. Pex- idartinib is the first CSF-1 receptor inhibitor approved for the treatment of TGCT. Here, we discuss various available treatment strategies and ongoing investigations and trials targeting diffuse TGCT, which include nilotinib, lacnotuzu- mab, cabiralizumab, vimseltinib, and emactuzumab.

News (Medical) associated with Cabiralizumab

02 Jan 2023

·www.prnewswire.com

Propulsion of Pancreatic Cancer Pipeline as Novel and Extensive 170+ Therapies Likely to Enter in the Treatment Domain | DelveInsight

The prevalence of pancreatic cancer has been rising since the past few years, which prompts the growing demand for treatment options. The increasing prevalence of cancer, the robust pipeline, and the growing research and development activities to develop novel therapies to treat Pancreatic Cancer drive the market. The companies developing the potential therapies in the last stage of development include FibroGen, Eli Lilly and Company, CARsgen Therapeutics, and several others. LAS VEGAS, Jan. 2, 2023 /PRNewswire/ -- DelveInsight's ' Pancreatic Cancer Pipeline Insight – 2022 ' report provides comprehensive global coverage of available, marketed, and pipeline pancreatic cancer therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the pancreatic cancer pipeline domain. Key Takeaways from the Pancreatic Cancer Pipeline Report DelveInsight's pancreatic cancer pipeline report depicts a robust space with 150+ active players working to develop 170+ pipeline therapies for pancreatic cancer treatment. Key pancreatic cancer companies such as FibroGen, Innovent Biologics, CARsgen Therapeutics, Ascentage Pharma, NGM Biopharmaceuticals, TME Pharma AG, Lee's Pharmaceutical Limited, ImmunityBio, Inc., Rgene Corporation, CSPC ZhongQi Pharmaceutical Technology Co., Ltd., CanBas Co. Ltd., Jiangsu HengRui Medicine Co., Ltd., Bristol-Myers Squibb, SynerGene Therapeutics, Inc., AbbVie, Silenseed Ltd, Galera Therapeutics, Inc., Helix BioPharma, Golden Biotechnology Corporation, Eli Lilly and Company, Innovent Biologics (Suzhou) Co. Ltd., Panbela Therapeutics, Inc., GlaxoSmithKline, Chia Tai Tianqing Pharmaceutical Group, Roche, Prestige Biopharma Limited, Everfront Biotech Co., Ltd., XBiotech, Inc., Incyte Corporation, Ability Pharmaceuticals SL, Lokon Pharma, HCW Biologics, Amplia Therapeutics Limited, BioLineRx, Ltd., Taiho Pharmaceutical, Sanofi, Scandion Oncology, Nelum, Celldex Therapeutics, Merus N.V., Seagen Inc., GC Cell Corporation, MetiMedi Pharmaceuticals, Lumicell, Nuvation Bio Inc., ENB Therapeutics, BioNTech SE, Bayer, Genentech, Inc., Rise Biopharmaceuticals, Inc., Prestige Biopharma Limited, iOnctura, Shanghai Unicar-Therapy Bio-medicine Technology, Shanghai Hengrui Pharmaceutical Co., Ltd., Hangzhou Neoantigen Therapeutics Co., Ltd., EUSA Pharma, Inc.,Agenus Inc., Arcus Biosciences, Inc.Amgen, Biomea Fusion, and others are evaluating pancreatic cancer drugs to improve the treatment landscape. Promising pancreatic cancer pipeline therapies in various stages of development include Pamrevlumab, Niraparib, CT041, APG-1387, BNT141, ENB003, NUV-868, MCLA-128, LUM015, tisotumab vedotin, OMT-111, tusamitamab ravtansine, SCO-101, NGM120, CDX-301, NLM-001, TAS 102, Olaptesed pegol, BL-8040, Gimatecan, AMP945, N-803, HCW9218, BLEX 404, delolimogene mupadenorepvec, Mitoxantrone Hydrochloride Liposome injection, ABTL0812, CBP501, Pemigatinib, SHR-1701, Fluzoparib, XB2001, Cabiralizumab, EF-009, SGT-53, ABBV-927, PBP1510, Vemurafenib, siG12D-LODER, Penpulimab, GC4711, GSK2256098, L-DOS47, SBP-101, Antroquinonol, LY3214996, Sintilimab, RP72, PBP1510, IOA-289, U87, MVT-5873, SHR-A1904, iNeo-Vac-P01, iNeo-Vac-P01, TQB2858, Siltuximab, AGEN1423, AB680, AMG 199, BMF-219, and others. In December 2022, Targovax ASA announced that it has entered into a collaboration agreement with The University of Kansas Cancer Center (KU Cancer Center) and Agenus Inc. to run a clinical trial testing mutant RAS vaccine TG01 in combination with PD-1 CPI balstilimab in pancreatic cancer following surgery and standard-of-care (SoC) chemotherapy. In December 2022, Bluestar Genomics, Inc. announced the initiation of the New Onset Diabetes Management for Earlier Detection (NODMED) trial, one of the largest clinical studies in pancreatic cancer to date. The trial will use Bluestar Genomics' proprietary epigenomic methods for the detection of the disease. In December 2022, iOnctura BV, a clinical-stage biotech developing novel cancer therapies, had been granted €17.5 million ($18.6 million) funding from the European Investment Council's (EIC) accelerator program to develop IOA-289 for pancreatic cancer.The EIC's funding consists of a grant of €2.5 million ($2.7 million) and €15 million ($16 million) of equity investment. In December 2022, In the Phase I/II CodeBreaK 100 trial, the KRAS G12C inhibitor sotorasib achieved meaningful anticancer activity with an acceptable safety profile in heavily pretreated patients with KRAS G12C-mutated metastatic pancreatic cancer, according to researchers at The University of Texas MD Anderson Cancer Center. The results of the trial, published in the The New England Journal of Medicine, indicate an objective response rate of 21.1% and a median time-to-response of 1.5 months, with 84% of patients experiencing disease control. Median progression-free survival was 4 months, and overall survival was 6.9 months. In December 2022, Oncolytics Biotech® Inc. announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to pelareorep in combination with Roche's anti-PD-L1 checkpoint inhibitor atezolizumab, and the chemotherapeutic agents gemcitabine and nab-paclitaxel, for the treatment of advanced/metastatic pancreatic ductal adenocarcinoma (PDAC). This represents pelareorep's second FDA Fast Track designation. In December 2022, RemeGen Co., Ltd. announced that its latest antibody-drug conjugate (ADC), RC118 for injection, has been granted two orphan drug designations (ODD) by the United States Food and Drug Administration (FDA) for gastric cancer (including gastroesophageal junction cancer) and pancreatic cancer. This marks the Company's fourth, having previously been granted ODD twice for Disitamab Vedotin (RC48) and Telitacicept (RC18) earlier this year. In December 2022, Panbela Therapeutics, Inc. announced that the European Medicines Agency (EMA) Committee for Orphan Medicinal Products issued a positive opinion on Panbela's application for orphan designation of ivospemin ( SBP-101) in combination with gemcitabine and nab-Paclitaxel in patients with metastatic pancreatic ductal adenocarcinoma (PDA). In September 2022, Qualigen Therapeutics, Inc. announced the presentation of two posters on QN-302 at the AACR 8th Special Conference on Pancreatic Cancer. The data presented include information on the compound's safety, tolerability, and efficacy in a pancreatic cancer model. The poster included preclinical toxicology data that showed QN-302 does not produce adverse toxicological reactions in mouse models at therapeutic doses. In in vitro tests, QN-302 inhibits acetylcholinesterase (AChE) by 53% and muscarinic receptor (M2) by 70% at 1 µM. Request a sample and discover the recent advances in pancreatic cancer drugs @ Pancreatic Cancer Pipeline Report The pancreatic cancer pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage pancreatic cancer drugs, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the pancreatic cancer clinical trial landscape. Pancreatic Cancer Overview Pancreatic cancer develops in the pancreas tissues, an abdomen organ located behind the stomach's bottom portion. The pancreas secretes hormones that help control blood sugar and enzymes that aid digestion. Pancreatic cancer is a condition in which malignant (cancer) cells develop in pancreatic tissues. The pancreas can develop tumors in various ways, including malignant and noncancerous tumors. However, the precise causes of pancreatic cancer are unknown. Individuals diagnosed with pancreatic cancer before the tumor develops or spreads have an average life expectancy of pancreatic cancer of 3 to 3.5 years. Pancreatic cancer symptoms may include jaundice, dark urine, weight loss, loss of appetite, fatigue, and others. A pancreatic cancer diagnosis is difficult because symptoms are frequently confused with those of other disorders, such as irritable bowel syndrome. The extent of the cancer determines the treatment of pancreatic cancer options. Pancreatic cancer treatment options may include surgery, chemotherapy, radiation therapy, targeted therapy, or a combination of these. Learn more about the diseases and pancreatic cancer diet @ Pancreatic Cancer Tests A snapshot of the Pancreatic Cancer Pipeline Drugs mentioned in the report: Learn more about the emerging pancreatic cancer treatment options @ Pancreatic Cancer Clinical Trials Pancreatic Cancer Therapeutics Assessment The pancreatic cancer pipeline report proffers an integral view of pancreatic cancer emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Pancreatic Cancer Pipeline Report Coverage: Global Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Therapeutics Assessment By Route of Administration: Inhalation, Intranasal, Intravenous, Oral, Parenteral, Subcutaneous Therapeutics Assessment By Molecule Type: Antibody, Antisense oligonucleotides, Immunotherapy, Monoclonal antibody, Peptides, Protein, Recombinant protein, Small molecule, Stem Cell, Vaccine Therapeutics Assessment By Mechanism of Action: Connective tissue growth factor inhibitors, Poly(ADP-ribose) polymerase 1 inhibitors, Poly(ADP-ribose) polymerase 2 inhibitors, Immunologic cytotoxicity, T lymphocyte replacements, Growth differentiation factor 15 inhibitors, Endothelin B receptor antagonists, Image enhancers Key Pancreatic Cancer Companies: FibroGen, Innovent Biologics, CARsgen Therapeutics, Ascentage Pharma, NGM Biopharmaceuticals, TME Pharma AG, Lee's Pharmaceutical Limited, ImmunityBio, Inc., Rgene Corporation, CSPC ZhongQi Pharmaceutical Technology Co., Ltd., CanBas Co. Ltd., Jiangsu HengRui Medicine Co., Ltd., Bristol-Myers Squibb, SynerGene Therapeutics, Inc., AbbVie, Silenseed Ltd, Galera Therapeutics, Inc., Helix BioPharma, Golden Biotechnology Corporation, Eli Lilly and Company, Innovent Biologics (Suzhou) Co. Ltd., Panbela Therapeutics, Inc., GlaxoSmithKline, Chia Tai Tianqing Pharmaceutical Group, Roche, Prestige Biopharma Limited, Everfront Biotech Co., Ltd., XBiotech, Inc., Incyte Corporation, Ability Pharmaceuticals SL, Lokon Pharma, HCW Biologics, Amplia Therapeutics Limited, BioLineRx, Ltd., Taiho Pharmaceutical, Sanofi, Scandion Oncology, Nelum, Celldex Therapeutics, Merus N.V., Seagen Inc., GC Cell Corporation, MetiMedi Pharmaceuticals, Lumicell, Nuvation Bio Inc., ENB Therapeutics, BioNTech SE, Bayer, Genentech, Inc., Rise Biopharmaceuticals, Inc., Prestige Biopharma Limited, iOnctura, Shanghai Unicar-Therapy Bio-medicine Technology, Shanghai Hengrui Pharmaceutical Co., Ltd., Hangzhou Neoantigen Therapeutics Co., Ltd., EUSA Pharma, Inc.,Agenus Inc., Arcus Biosciences, Inc., Amgen, Biomea Fusion, and others. Key Pancreatic Cancer Pipeline Therapies: Pamrevlumab, Niraparib, CT041, APG-1387, BNT141, ENB003, NUV-868, MCLA-128, LUM015, tisotumab vedotin, OMT-111, tusamitamab ravtansine, SCO-101, NGM120, CDX-301, NLM-001, TAS 102, Olaptesed pegol, BL-8040, Gimatecan, AMP945, N-803, HCW9218, BLEX 404, delolimogene mupadenorepvec, Mitoxantrone Hydrochloride Liposome injection, ABTL0812, CBP501, Pemigatinib, SHR-1701, Fluzoparib, XB2001, Cabiralizumab, EF-009, SGT-53, ABBV-927, PBP1510, Vemurafenib, siG12D-LODER, Penpulimab, GC4711, GSK2256098, L-DOS47, SBP-101, Antroquinonol, LY3214996, Sintilimab, RP72,PBP1510, IOA-289, U87, MVT-5873, SHR-A1904, iNeo-Vac-P01, iNeo-Vac-P01, TQB2858, Siltuximab, AGEN1423, AB680, AMG 199, BMF-219, and others. Dive deep into rich insights for pancreatic cancer research; visit @ New Treatment for Pancreatic Cancer Table of Contents For further information on pancreatic cancer prevention, reach out @ Pancreatic Cancer Drug Treatment Related Reports Pancreatic Cancer Epidemiology Pancreatic Cancer Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical, and forecasted pancreatic cancer epidemiology in the 7MM. Pancreatic Cancer Market Pancreatic Cancer Market Insight, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the market trends, market drivers, market barriers, and key pancreatic cancer companies, including FibroGen, NeoImmuneTech, NOXXON Pharma, Silenseed Ltd., Amgen, NGM Biopharmaceuticals, among others. Advanced Pancreatic Cancer Market Advanced Pancreatic Cancer Market Insight, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the market trends, market drivers, market barriers, and key advanced pancreatic cancer companies, including AstraZeneca, Merck Sharp & Dohme LLC, Bayer, Roche, among others. Advanced Pancreatic Cancer Pipeline Advanced Pancreatic Cancer Pipeline Insight – 2022 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key advanced pancreatic cancer companies, including FibroGen, NeoImmuneTech, NOXXON Pharma, Silenseed Ltd., Amgen, NGM Biopharmaceuticals, among others. Metastatic Pancreatic Cancer Market Metastatic Pancreatic Cancer Market Insight, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the market trends, market drivers, market barriers, and key metastatic pancreatic cancer companies, including Takeda Oncology, Salspera, Eli Lilly and Company, among others. Metastatic Pancreatic Cancer Pipeline Metastatic Pancreatic Cancer Pipeline Insight – 2022 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key metastatic pancreatic cancer companies, including Takeda Oncology, Salspera, Eli Lilly and Company, among others. Other Trending Oncology Reports Follicular lymphoma | Indolent lymphoma | Severe Toxicities In Lymphoma | Marginal Zone Lymphoma | Vulvar Squamous Cell Carcinoma | Cholangiocarcinoma | Metastatic Cutaneous Squamous cell Carcinoma | Nasopharyngeal Carcinoma | Ductal Carcinoma in Situ | Oncolytic Virus Cancer Therapy | Cancer Cachexia | Intratumoral Cancer Therapies | Brain Cancer Related Healthcare Blogs Upcoming Oncology Drugs Oncology Market Outlook Future of Oncology Market Related Cases Studies Competitive Intelligence Market Assessment Product Assessment Epidemiology Assessment Related Healthcare Services Healthcare Business Consulting Healthcare Competitive Intelligence Services Healthcare Asset Prioritization Services About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. Connect with us at LinkedIn Contact Us Shruti Thakur [email protected] +1(919)321-6187 Logo: SOURCE DelveInsight Business Research, LLP

Fast TrackOrphan DrugClinical ResultImmunotherapy

04 Mar 2021

·medcitynews.com

Amgen’s $1.9B Five Prime deal adds to cancer drug pipeline and Asia strategy

Amgen, which is looking to bolster its cancer drug pipeline and build its presence in Asia, is acquiring Five Prime Therapeutics in a $1.9 billion deal that checks off both goals. On Thursday, Amgen announced it has agreed to pay $38 cash for each share of Five Prime, a more than 70 percent premium to the company’s closing stock price on Wednesday. Five Prime develops immuno-oncology drugs and targeted cancer therapies. The jewel of the South San Francisco-based biotech’s pipeline is bemarituzumab (usually shortened to “bema”), an antibody ready to advance to Phase 3 testing in gastric cancer. “This deal advances our strategic imperative to grow our business internationally, and in Asia-Pacific in particular, where gastric cancer is highly prevalent and where we previously stated we expect to generate roughly 25% of revenue growth over the next 10 years,” Amgen Chief Financial Officer Peter Griffin said on a conference call. For Five Prime, acquisition by the Thousand Oaks, California-based pharma giant represents a lifeline following a series of clinical and financial setbacks in recent years that left much of the biotech’s fortunes resting on its lead antibody drug. Gastric cancer accounts for more than one million cancer diagnoses globally and is the third leading cause of cancer deaths worldwide, trailing only lung and colorectal cancers. Five Prime does not aim to address all gastric cancers. The company designed bema to target fibroblast growth factor receptor 2 (FGFR2), a tumor growth protein overexpressed in an estimated 10% of gastric cancer patients. In 2019, with encouraging safety results from a small Phase 1 study, Five Prime set out to jump straight into Phase 3. The company began enrolling patients, while at the same time hunting for a partner that could execute the full clinical trial. According to Five Prime’s 2019 annual report, the plan was to conduct an early analysis to assess efficacy of the treatment. Depending on the outcome, the company could continue the trial as a Phase 3 test, stop the study, or amend the clinical trial design. Five Prime noted in the report that even if it received clearance from the independent data monitoring committee to proceed with the Phase 3 plan, carrying out that study would require securing a pharma partner to pay for it. But potential partners told the company it was unlikely to land a collaborator without data from previously untreated patients with gastric or gastroesophogeal cancers. Last year, the company pivoted from its Phase 3 plan and instead began a randomized Phase 2 study. The Phase 2 results came through last November, showing that the Five Prime drug, in combination with standard of care chemotherapy, met the study’s main goals compared to treatment with chemotherapy alone. But the results were not without problems. Inflammation of the cornea, as well as stomatitis, which is inflammation of the mouth and lips, were higher in the bema group. Also, more patients dropped out of the treatment group than the control arm. David Reese, Amgen’s executive vice president of research and development, said corneal inflammation was not unexpected because the protein that bema targets is also expressed on corneal cells. That problem can be addressed in future studies with eye drops. Reese added that stomatitis was less of a driver in patients dropping out of the study. The inflammation is a known side effect of the chemotherapy, he said. Amgen will proceed with a Phase 3 test of bema. Gastric cancer is the lead target, but Reese said the pharma giant will also explore other cancers driven by FGFR2b, such as squamous cell carcinoma of the lung, breast and ovarian cancers, and other solid tumors. Looking further down the road, Reese said Amgen would explore combinations with other types of cancer drugs, such as checkpoint inhibitors and tyrosine kinase inhibitors. Acquisition by Amgen marks the latest twist in a long road for Five Prime. Founded in 2002 by Bay Area biotech veteran Lewis “Rusty” Williams, the company set out with drug discovery technology that identified proteins on cells that contribute to disease. The company used that technology to design protein drugs addressing those targets, leveraging the platform into partnerships with bigger companies including GlaxoSmithKline, UCB, and Bristol Myers Squibb. In 2013, with drugs for inflammatory diseases and cancer in clinical testing, Williams took Five Prime public, raising $62.4 million in an IPO priced at $13 per share. Some of Five Prime’s drugs found their way into testing in combination with cancer therapies from its partners. Cabiralizumab, a Five Prime antibody developed to block a protein called colony-stimulating factor-1, was tested in combination with BMS’s nivolumab. But the drug disappointed in 2017 after data from an early-stage test showed higher than expected toxicity. In early 2019, Five Prime restructured to save cash. Jobs in research, pathology, and manufacturing were eliminated. Later that year, the biotech restructured again and eliminated most of its workers involved in discovering drug targets and creating therapeutic proteins. According to a Five Prime securities filing, most of the company’s lab equipment was auctioned off last April. Five Prime implemented the corporate shakeups to keep its focus on the cancer drugs that had already reached clinical testing. Cabiralizumab was still one of those drugs. But a little more than a year ago, the antibody failed a mid-stage study in pancreatic cancer. BMS had acquired rights to that drug as part of an alliance that started in 2015. After the Phase 2 failure, the pharma giant said it would not sponsor additional tests of that Five Prime antibody. At that point, shares of Five Prime were trading at around $4.50 each. BMS remains a partner on two other Five Prime cancer programs. SeaGen is the company’s only other remaining collaborator, with an antibody drug conjugate in preclinical development for an undisclosed disease target. In 2017, Zai Labs licensed rights to develop and commercialize bema in China, Hong Kong, Macau, and Taiwan. The Shanghai-based company is responsible for developing and commercializing the drug in those markets. Amgen will inherit that agreement and will receive a royalty on Zai Lab’s future net sales. Among Five Prime’s programs, partnered and internal, Bema was furthest along in clinical development. Amgen will evaluate Five Prime’s earlier-stage programs on an asset-by-asset basis, Reese said. Bema is set to join an Amgen pipeline that has gastric cancer drug candidates in early clinical development. AMG199 addresses gastric cancer that overexpresses the protein mucin-17. AMG910 is in development for gastric cancer that expresses the protein CLDN18.2. Reese said that the Five Prime drug is appropriate for Amgen’s strategy to develop targeted cancer therapies. “One of our beliefs is that the future of oncology broadly is the marriage of immuno-oncology and precision medicine targeting specific molecular alterations, and I think this fits nicely within that broader strategic rubric in a complement to the other assets in our portfolio,” he said. The boards of directors of both companies have approved the transaction, which is expected to close in the second quarter of this year. If Five Prime receives a superior offer, or if the company backs out of the agreement, it must pay Amgen a $76 million termination fee, according to terms of the merger agreement.

CollaborateAntibodyAcquisitionIPO

11 Mar 2016

·www.biospace.com

Bad News for Bay Area’s Five Prime as GlaxoSmithKline Walks Away from Cancer Drug Pact

March 11, 2016 By Alex Keown , BioSpace.com Breaking News Staff SOUTH SAN FRANCISCO – GlaxoSmithKline is terminating its five-year developmental partnership with California-based Five Prime Therapeutics for the early-stage cancer drug FP-1039, which was being studied for non-small cell lung cancer and mesothelioma, Five Prime announced Thursday. On March 10, Five Prime said London-based GlaxoSmithKline notified the company that it was providing its 180-day notice of termination of the FP-1039 license and collaboration agreement for convenience. In January, GlaxoSmithKline and Five Prime abandoned its squamous non-small cell lung cancer trial with FP-1039, but continued to focus on a trial for mesothelioma. Five Prime said it plans to work with GSK to “ensure completion of enrollment in the ongoing mesothelioma arm of the Phase 1b study and to transfer the asset and program back to Five Prime.” Five Prime said it will base decisions on future development of FP-1039 for mesothelioma on “whether the quality and durability of responses in this population is maintained in this trial.” GlaxoSmithKline has submitted the mesothelioma data for presentation at the ASCO 2016 annual meeting, Five Prime said. Although GSK terminated its relationship, Five Prime’s stock is up more than 6 percent this morning, trading at $32.95 per share. The stock increase followed Five Prime’s 2015 fourth quarter financial report showing revenue of $363.3, beating analysts’ estimates of $354.8 million, the Associated Press reported. For the full year Five Prime posted net income of $249.6 million. Since the start of 2016, Five Prime’s stock is down about 20 percent. The stock started the year trading at $41.50 per share. In February, the stock hit a low of $29.04 per share. Lewis T. “ Rusty ” Williams , president and chief executive officer of Five Prime, called 2015 a transformational year for the company. Although the GSK agreement is coming to an end, Williams touted its ongoing partnership with Bristol-Myers Squibb for the development and commercialization of its experimental FPA008 therapy. He said the agreement “maximizes the clinical and commercial potential of FPA008” and the “exceptional terms have strengthened our financial position.” In October, Five Prime secured an immuno-oncology deal with Bristol-Myers Squibb worth $1.74 billion. The deal is for the development and commercialization of Five Prime’s colony stimulating factor 1 receptor (CSF1R) antibody program, including FPA008 which is in Phase 1 development for immunology and oncology indications. That deal replaced a previous one between the two companies to combine Opdivo (nivolumab), Bristol-Myers Squibb’s programmed-death 1 (PD-1) immune checkpoint inhibitor, with FPA008 in six tumor types. FPA008 is an investigational antibody that inhibits CSF1R and has been shown in preclinical models to block the activation and survival of monocytes and macrophages. In addition to the Bristol-Myers deal, Williams said the company is encouraged by early data from its experimental gastric cancer treatment FPA144. FPA144 is an anti-FGF receptor 2b (FGFR2b) monoclonal antibody that is engineered to recruit NK cells into the tumor microenvironment. In January, Five Prime presented clinical data for FPA144 that showed two partial responses in six gastric cancer patients with IHC 3+ FGFR2b-positive gastric cancer, as well as a partial response in a patient whose bladder cancer overexpressed FGFR2b. “Beyond our clinical programs, we also made progress in our internal immuno-oncology research programs, and continue to be on track to IND application in 2017,” Williams said in a statement.

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Indication	Highest Phase	Country/Location	Organization	Date
Triple Negative Breast Cancer	Phase 2	United States	Bristol Myers Squibb Co.	19 Nov 2020
Biliary Tract Neoplasms	Phase 2	-	Bristol Myers Squibb Co.	14 Jun 2019
Peripheral T-Cell Lymphoma	Phase 2	United States	Bristol Myers Squibb Co.	25 Apr 2019
Pancreatic Cancer	Phase 2	United States	Bristol Myers Squibb Co.	18 Dec 2017
Pancreatic Cancer	Phase 2	Japan	Bristol Myers Squibb Co.	18 Dec 2017
Pancreatic Cancer	Phase 2	Canada	Bristol Myers Squibb Co.	18 Dec 2017
Pancreatic Cancer	Phase 2	Denmark	Bristol Myers Squibb Co.	18 Dec 2017
Pancreatic Cancer	Phase 2	Germany	Bristol Myers Squibb Co.	18 Dec 2017
Pancreatic Cancer	Phase 2	Italy	Bristol Myers Squibb Co.	18 Dec 2017
Pancreatic Cancer	Phase 2	Spain	Bristol Myers Squibb Co.	18 Dec 2017

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03336216 (CTgov)	Phase 2	Pancreatic Cancer	205	nab-paclitaxel+Leucovorin+gemcitabine+Irinotecan+5-Fluorouracil (Arm A: Investigator Choice)	avalrnhexy(zemsmcvfpy) = ytwmrfujlt clfiheiatu (ujlmzlcmuc, qtaevvzxjl - qxbafwtpju) View more	-	23 Jul 2024
				Cabiralizumab+Nivolumab (Arm B: Cabiralizumab + Nivolumab)	avalrnhexy(zemsmcvfpy) = urzivsegpt clfiheiatu (ujlmzlcmuc, hmdntgudqg - jbupoxysjv) View more
NCT04331067 (CTgov)	Phase 1/2	Triple Negative Breast Cancer	15	Tumor biopsy+Cabiralizumab+Nivolumab+Paclitaxel+Carboplatin (Arm B: Neoadjuvant Chemo + Nivolumab + Cabiralizumab)	phmmeouifh(punfwaskin) = riwfxvkhyf fudfbhfizg (jziofnelvt, 82.5) View more	-	16 May 2024
				Tumor biopsy+Nivolumab+Paclitaxel+Carboplatin (Arm A: Neoadjuvant Chemo + Nivolumab)	iqmvnybspb = cocqmmapgj aoliwdqqrz (fvmzbgivvc, clssxnstfl - eybpbyqqla) View more
NCT03502330 (Pubmed \| Mol Cancer)	Phase 1	-	-	Cabiralizumab (anti-CSF1R)	ogtpjwspcz(smdwzqdcnj) = pvpwiwygft txxmnobzhu (wppzdsujho ) View more	Negative	14 Nov 2023
				Sotigalimab (CD40-agonist)	ogtpjwspcz(smdwzqdcnj) = pjhcekstgx txxmnobzhu (wppzdsujho ) View more
NRG BR001 (ASTRO2022)	Phase 1	-	207	Nivolumab/Urelumab	axcxvmyfos(ormyaedigg) = There were 3 grade 5 AEs: 2 respiratory failures and 1 pulmonary hemorrhage that were rated possibly treatment related wnszpyreqv (ltiuijcsxx ) View more	Positive	01 Nov 2022
				Nivolumab/Cabiralizumab
NCT03599362 (CTgov)	Phase 2	Pancreatic carcinoma non-resectable	7	Stereotactic Body Radiotherapy (SBRT)+Cabiralizumab+Nivolumab	tnondrzlvo = nuvgofuhwl gkzpzwtugw (yhynhcqxug, axhxlxlqxc - ycafdcumtf) View more	-	19 Oct 2021
NCT03927105 (CTgov)	Phase 2	Peripheral T-Cell Lymphoma	4	cabiralizumab+Nivolumab	txgtodylir = zupgispbsg dimngpzarp (sidhsgggnj, qralpqmoif - zqpamkoqbm) View more	-	10 Sep 2021
NCT03502330 (Pubmed \| Clin Cancer Res) Manual	Phase 1	Melanoma \| Non-Small Cell Lung Cancer \| Kidney Neoplasms	26	Sotigalimab+Cabiralizumab+Nivolumab	sozlimydyv(pvmhtjsldt) = asymptomatic elevations of lactate dehydrogenase (n = 26), creatine kinase (n = 25), aspartate aminotransferase (n = 25), and alanine aminotransferase (n = 19); periorbital edema (n = 17); and fatigue (n = 13) yqfkovnfun (zqnnzfdlda ) View more	Positive	01 Sep 2021
NCT02471716 (FPA008-002, CTgov)	Phase 1/2	Pigmented Villonodular Synovitis	66	FPA008 (Phase 1 FPA008 Dose Escalation 1mg/kg)	zidccezlkh = zqwwsygkhm ikavibrkhw (dvszxztfwv, aumiyhtvby - nwojnfbhim) View more	-	31 Aug 2021
				FPA008 (Phase 1 FPA008 Dose Escalation 2mg/kg)	zidccezlkh = ikdqvrowcl ikavibrkhw (dvszxztfwv, evyuyxcroi - yvbbholtkn) View more
NCT03431948 (Pubmed \| Clin Cancer Res) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	60	SBRT+Nivolumab+Urelumab or Cabiralizumab	qtmcjysucw(olqckvcgtw) = sewvivnizt equeblowab (ouklhpyvqm ) View more	Positive	24 Jun 2021
NCT03158272 (CTgov)	Phase 1	Advanced cancer	19	cabiralizumab (M1 Cohort)	jekxpxlqbi = anzqkjtfrw aeozqttzon (tjkzruaipk, edzvqdbfyi - mgsdnwlrvj) View more	-	21 Dec 2020
				cabiralizumab (M2 Cohort)	jekxpxlqbi = nzysejbtsz aeozqttzon (tjkzruaipk, gmaezoppju - yayrpehqzw) View more

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