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 2

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 Oct 2023·International journal of radiation oncology, biology, physics

Predictors of Hepatotoxicity in Patients with Metastatic Solid Tumors Treated with Immune Checkpoint Inhibition (ICI) and Liver-Directed SBRT.

Article

Author: Lynch, C ; Juloori, A ; Chmura, S J ; Bestvina, C M ; Pitroda, S P ; Katipally, R R ; Korpics, M C

PURPOSE/OBJECTIVE(S):

Liver-metastasis-directed SBRT (LM-SBRT) alone provides durable local control for liver metastases with low rates of toxicity when adhering to established dose constraints. Whether these constraints are sufficient in the context of concurrent ICI is not established. To determine whether LM-SBRT contributes to hepatotoxic adverse events (HAE) in patients receiving ICI, we analyzed potential predictors of HAE in a prospectively evaluated cohort of clinical trial patients treated with both SBRT and ICI.

MATERIALS/METHODS:

Patients with metastatic solid tumors were included from three trials of multi-site SBRT with ICI given concurrently or shortly after SBRT provided they received all study treatments and were monitored for adverse events. ICI agents included pembrolizumab alone or dual agent ICI with nivolumab and either cabiralizumab, urelumab, or ipilimumab. LM-SBRT was delivered to 45 Gy in 3 fr with mean liver dose (MLD) limited to 16 Gy and <700 cc of liver receiving 17.1 Gy. HAE were defined using CTCAE 4.0 as: elevation of AST, ALT, bilirubin or alkaline phosphatase; autoimmune hepatitis; hepatic failure; or cholecystitis. HAE were included if rated at least possibly related to treatment by the trial monitoring committee. Cumulative incidence (CI) of HAE was modeled with death as a competing risk. Competing risks regression was performed using Fine-Gray modeling.

RESULTS:

Two hundred thirteen patients were evaluable. Median follow-up was 10 months. Median age was 61, 90 had liver metastases at treatment, 65 received SBRT to a liver lesion, 15 had underlying liver disease (cirrhosis or hepatic steatosis) and 13 patients had a primary liver cancer. Dual agent ICI was given to 97 patients. Table 1 shows CI at 6 months of grades 1-4 HAE in all patients, LM-SBRT patients and non-liver SBRT patients (NL-SBRT). None experienced grade 5 HAE. There was no significant difference in CI of any grade of HAE between LM-SBRT and NL-SBRT patients. This was also true when comparing LM-SBRT patients to NL-SBRT patients with <0.1 Gy MLD. ICI dose reduction or cessation due to HAE occurred in 4 patients, none of whom received LM-SBRT. On univariate analysis, underlying liver disease and dual agent ICI were significantly associated with grade 2+ HAE while age, LM-SBRT, MLD, primary liver cancer and presence of liver metastases at treatment were not. On multivariate analysis, underlying liver disease and dual agent ICI remained significantly associated with grade 2+ HAE (HR: 6.7, 95% CI 2.3 - 19.1; 4.7, 95% CI 1.7 - 13.0). LM-SBRT and MLD were not significant on MVA.

CONCLUSION:

LM-SBRT did not significantly increase the risk for hepatotoxicity in patients receiving ICI when respecting the above dose constraints. Risk for hepatotoxicity appears to be driven by dual agent ICI and underlying liver disease.

15 Oct 2021·Clinical cancer research : an official journal of the American Association for Cancer ResearchQ1 · MEDICINE

Phase I Study of Stereotactic Body Radiotherapy plus Nivolumab and Urelumab or Cabiralizumab in Advanced Solid Tumors

Q1 · MEDICINE

Article

Author: Fleming, Gini F. ; Moroney, John W. ; Janisch, Linda A. ; Hahn, Olwen M. ; Foster, Corey C. ; Dai, Julia ; Desai, Ami V. ; Pitroda, Sean P. ; Luke, Jason J. ; Polite, Blase N. ; Chmura, Steven J. ; Nanda, Rita ; Hseu, Robyn ; Vokes, Everett E. ; Liao, Chih-Yi ; Kindler, Hedy L. ; Ratain, Mark J. ; Hoffman, Mark D. ; Weichselbaum, Ralph R. ; Karrison, Theodore G. ; O'Donnell, Peter H.

Abstract:

Purpose::

CD137 agonism and CSF1R blockade augment stereotactic body radiotherapy (SBRT) and anti-programmed death-1 in preclinical models. We evaluated the safety and efficacy of SBRT with nivolumab+urelumab (CD137 agonist) or nivolumab+cabiralizumab (CSF1R inhibitor).

Patients and Methods::

This phase I clinical trial enrolled patients with advanced solid tumors that had progressed on standard therapies. SBRT was delivered to 1–4 metastases with nivolumab+urelumab or nivolumab+cabiralizumab given concurrently and following SBRT. Dose-limiting toxicity (DLT) was the primary endpoint with anatomic location-specific SBRT doses deemed safe if ≤33% DLT frequency was observed. Secondary endpoints included RECISTv1.1 response, progression-free survival (PFS), overall survival (OS), and molecular correlative studies.

Results::

Sixty patients were enrolled, and median follow-up for living patients is 13.8 months. Of these, 23 (38%) received SBRT+nivolumab+urelumab and 37 (62%) received SBRT+nivolumab+cabiralizumab. Seven patients (12%) experienced a DLT (n = 3 grade 3, n = 4 grade 4) in the following anatomic cohorts: abdominal/pelvic (3/17, 18%), liver (1/13, 8%), central lung (2/14, 14%), and peripheral lung (1/12, 8%). Of 41 patients radiographically evaluable for best overall response including 55 radiated and 23 unirradiated RECIST target lesions, 2 had complete responses (5%), 7 had partial responses (17%), 12 had stable disease (29%), and 20 had progression (49%). Median estimated PFS and OS are 3.0 months [95% confidence interval (CI), 2.9–4.8] and 17.0 months (95% CI, 6.8–undetermined), respectively. No patients with elevated pre-SBRT serum IL8 experienced a response.

Conclusions::

SBRT to ≤4 sites with nivolumab+urelumab or nivolumab+cabiralizumab for treating advanced solid tumors is feasible with acceptable toxicity and modest antitumor activity.See related commentary by Rodriguez-Ruiz et al., p. 5443

01 Oct 2021·The American Journal of dermatopathologyQ4 · MEDICINE

Papillary Dermal Elastolysis Secondary to Combination Nivolumab and Cabiralizumab Therapy: Histiocytes and Dermal Mucin as Clues to the Diagnosis

Q4 · MEDICINE

Article

Author: Criscito, Maressa C ; Yin, Lu ; Lo Sicco, Kristen ; Haimovic, Adele ; Stokar, Evan ; Siolas, Despina ; Brinster, Nooshin K

Abstract::

Papillary dermal elastolysis has been described in the setting of experimental combination nivolumab and cabiralizumab immunotherapy. We report a third patient with distinctive, generalized atrophic macules that developed after a morbilliform eruption during a clinical trial for treatment of metastatic pancreatic adenocarcinoma. Histopathological findings demonstrated diminished elastic fibers in the papillary dermis, associated with a histiocyte-rich infiltrate and increased dermal mucin, features that should clue the dermatopathologist to this condition.

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

100 Deals associated with Cabiralizumab

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KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15082

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Biliary Tract Neoplasms	Phase 2	-	Bristol Myers Squibb Co.	14 Jun 2019
Biliary Tract Neoplasms	Phase 2	-	The Sidney Kimmel Comprehensive Cancer Center	14 Jun 2019
Peripheral T-Cell Lymphoma	Phase 2	US	Bristol Myers Squibb Co.	25 Apr 2019
Pancreatic Cancer	Phase 2	US	Bristol Myers Squibb Co.	19 Dec 2017
Pancreatic Cancer	Phase 2	JP	Bristol Myers Squibb Co.	19 Dec 2017
Pancreatic Cancer	Phase 2	CA	Bristol Myers Squibb Co.	19 Dec 2017
Pancreatic Cancer	Phase 2	DK	Bristol Myers Squibb Co.	19 Dec 2017
Pancreatic Cancer	Phase 2	DE	Bristol Myers Squibb Co.	19 Dec 2017
Pancreatic Cancer	Phase 2	IT	Bristol Myers Squibb Co.	19 Dec 2017
Pancreatic Cancer	Phase 2	KR	Bristol Myers Squibb Co.	19 Dec 2017

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04331067 (CTgov)	Phase 1/2	Triple Negative Breast Cancer	15	Tumor biopsy+Cabiralizumab+Nivolumab+Carboplatin+Paclitaxel (Arm B: Neoadjuvant Chemo + Nivolumab + Cabiralizumab)	ccpuysudzf(xwrkjkrafa) = riteqessct wlfvkwnrbc (kzbifxqohi, adxcerftqf - vfqlqrocwz) View more	-	16 May 2024
NCT04331067 (CTgov)	Phase 1/2	Triple Negative Breast Cancer	15	Tumor biopsy+Nivolumab+Carboplatin+Paclitaxel (Arm A: Neoadjuvant Chemo + Nivolumab)	mlaeigawpl(vjumlrnevb) = igbwgdccrc esxhqkxltx (wandodacxw, kiwprvgqlw - pjtbvxdjlp) View more	-	16 May 2024
NCT03599362 (CTgov)	Phase 2	Pancreatic carcinoma non-resectable	7	Stereotactic Body Radiotherapy (SBRT)+Cabiralizumab+Nivolumab	kvueuriucw(fqqeuprifb) = tbibifxdgb qqwuwvhoix (zvtosmoieu, qtyjmenrqd - ygwfwboocm) View more	-	19 Oct 2021
NCT03927105 (CTgov)	Phase 2	Peripheral T-Cell Lymphoma	4	cabiralizumab+Nivolumab	jftiokgqqh(oqlnwuimhq) = eegdklrxaz jxvzrwvzfn (vsaepcgcpn, gldcuhcofc - ondpvnklnb) 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	kzrtrmsxef(tngdhnszrl) = 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) ysovyplpdk (gsxuncqjvy ) View more	Positive	01 Sep 2021
NCT02471716 (CTgov)	Phase 1/2	Pigmented Villonodular Synovitis	66	FPA008 (Phase 1 FPA008 Dose Escalation 1mg/kg)	qjfsqtnkfy(sbpncgaqub) = tlzpheurrj kehazzxrmg (dqejcsftyk, cthndbodvj - plfjiatdcz) View more	-	31 Aug 2021
NCT02471716 (CTgov)	Phase 1/2	Pigmented Villonodular Synovitis	66	FPA008 (Phase 1 FPA008 Dose Escalation 2mg/kg)	qjfsqtnkfy(sbpncgaqub) = lsiacbbtwx kehazzxrmg (dqejcsftyk, jzoztmrysx - mcinzrhjke) View more	-	31 Aug 2021
NCT03431948 (Pubmed \| Clin Cancer Res) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	60	SBRT+Nivolumab+Urelumab or Cabiralizumab	vrltxotfjs(yejrozumau) = zwglbvymqo dleswdgamz (huyzkjpqll ) View more	Positive	24 Jun 2021
NCT03158272 (CTgov)	Phase 1	Advanced cancer	19	cabiralizumab (M1 Cohort)	aiqbjhtcyr(tstqvzzrom) = yfgbhmzxjl jbjsvqtisq (esnxrwxeqo, gcqoakilfe - smeeuijpez) View more	-	21 Dec 2020
NCT03158272 (CTgov)	Phase 1	Advanced cancer	19	cabiralizumab (M2 Cohort)	aiqbjhtcyr(tstqvzzrom) = tmrmlcmslc jbjsvqtisq (esnxrwxeqo, mvgvwdyzel - eevpureicq) View more	-	21 Dec 2020

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