PRINCETON, NJ, USA I December 15, 2023 IBristol Myers Squibb (NYSE: BMY) today announced that the Phase 3 RELATIVITY-123 trial evaluating the fixed-dose combination of nivolumab and relatlimab for the treatment of microsatellite stable (MSS) metastatic colorectal cancer (mCRC) patients whose disease has progressed following at least one, but no more than four, prior lines of therapy for metastatic disease will be discontinued due to futility based on a planned analysis conducted by an independent data monitoring committee. It was determined that the trial was unlikely to meet its primary endpoints upon completion.
The recommendation to stop the study was not based on safety concerns. The safety profile was consistent with previously reported studies of the fixed-dose combination of nivolumab and relatlimab.
Investigation of the fixed-dose combination of nivolumab and relatlimab as a treatment for other tumor types will continue as planned. These results do not impact the currently approved indication for patients with unresectable or metastatic melanoma.
“Metastatic colorectal cancer is a challenging cancer to treat with high unmet needs. Though there have been advances in treating patients with microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) colorectal cancers, patients with microsatellite stable (MSS) tumors continue to have limited treatment options in later lines of therapy. While we know immunotherapies have historically demonstrated limited efficacy in MSS colorectal cancers, we had hoped to demonstrate meaningful clinical benefit in this patient population and are disappointed in this outcome,” said Jeffrey Walch, M.D., Ph.D., vice president, global program lead, Bristol Myers Squibb. “We continue to be committed to the development of I-O therapies, including Opdivo (nivolumab) and Yervoy (ipilimumab), in MSI-H/dMMR colorectal cancers, and we thank the investigators, patients, and their loved ones who participated in this trial.”
The company will share the data with investigators so they may determine appropriate next steps for patients enrolled in the RELATIVITY-123 trial. The company will complete a full evaluation of the data and work with investigators to share the results with the scientific community.
About RELATIVITY-123
RELATIVITY-123 is a Phase 3 randomized, open label, multi-center trial evaluating the fixed-dose combination of nivolumab and relatlimab compared to regorafenib or trifluridine plus tipiracil (TAS-102) in approximately 700 adult patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC) whose disease has progressed following at least one but no more than four prior lines of therapy for metastatic disease. The study did not include patients with microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) tumors. The dual primary endpoints are overall survival (OS) in all randomized patients and in randomized patients with PD-L1 combined positive score (CPS) ≥ 1. Secondary endpoints include objective response rate (ORR), progression-free survival (PFS), and duration of response (DoR) by Blinded Independent Central Review per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, safety, and time until definitive deterioration-physical function and quality of life in all randomized patients and in randomized patients with PD-L1 CPS ≥ 1.
About LAG-3
Lymphocyte-activation gene 3 (LAG-3) is a cell-surface molecule expressed on effector T cells and regulatory T cells (Tregs) and functions to control T-cell response, activation and growth. LAG-3 inhibits the function of T cells when it interacts with the cell’s ligands and reduces the activation and growth of the cell on which it is found.
This T cell dysfunction allows tumors to avoid attack from the immune system and grow unchecked. Preclinical studies indicate that inhibition of LAG-3 may promote an anti-tumor response. Early research demonstrates that targeting LAG-3 in combination with other potentially complementary immune checkpoints may be a key strategy to more effectively potentiate anti-tumor immune activity.
Bristol Myers Squibb is evaluating relatlimab, its LAG-3-blocking antibody, in clinical trials in combination with other agents in a variety of tumor types.
About Colorectal Cancer
Colorectal cancer (CRC) is cancer that develops in the colon or the rectum, which are part of the body’s digestive or gastrointestinal system. Globally, CRC is the third most commonly diagnosed cancer in the world. In 2020, it is estimated that there were approximately 1,931,000 new cases of the disease and that it will be the second leading cause of cancer-related deaths among men and women combined.
Mismatch repair deficiency (dMMR) occurs when the proteins that repair mismatch errors in DNA replication are missing or non-functional, leading to microsatellite instability-high (MSI-H) tumors. Approximately 5-7% of metastatic CRC patients have dMMR or MSI-H tumors. The remaining 95% of colorectal cancer patients with microsatellite stable (MSS)/proficient mismatch repair (pMMR) tumors have limited treatment options in later-lines of therapy.
Bristol Myers Squibb: Creating a Better Future for People with Cancer
Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine and, through innovative digital platforms, are turning data into insights that sharpen their focus. Deep understanding of causal human biology, cutting-edge capabilities and differentiated research platforms uniquely position the company to approach cancer from every angle.
Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. As a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.
OPDUALAG U.S. INDICATION
Opdualag™ (nivolumab and relatlimab-rmbw) is indicated for the treatment of adult and pediatric patients 12 years of age or older with unresectable or metastatic melanoma.
Please see U.S. Full Prescribing Information for Opdualag.
About the Bristol Myers Squibb and Ono Pharmaceutical Collaboration
In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally, except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol Myers Squibb further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.
About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.
SOURCE: Bristol Myers Squibb
Post Views: 210
PRINCETON, NJ, USA I December 15, 2023 IBristol Myers Squibb (NYSE: BMY) today announced that the Phase 3 RELATIVITY-123 trial evaluating the fixed-dose combination of nivolumab and relatlimab for the treatment of microsatellite stable (MSS) metastatic colorectal cancer (mCRC) patients whose disease has progressed following at least one, but no more than four, prior lines of therapy for metastatic disease will be discontinued due to futility based on a planned analysis conducted by an independent data monitoring committee. It was determined that the trial was unlikely to meet its primary endpoints upon completion.
The recommendation to stop the study was not based on safety concerns. The safety profile was consistent with previously reported studies of the fixed-dose combination of nivolumab and relatlimab.
Investigation of the fixed-dose combination of nivolumab and relatlimab as a treatment for other tumor types will continue as planned. These results do not impact the currently approved indication for patients with unresectable or metastatic melanoma.
“Metastatic colorectal cancer is a challenging cancer to treat with high unmet needs. Though there have been advances in treating patients with microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) colorectal cancers, patients with microsatellite stable (MSS) tumors continue to have limited treatment options in later lines of therapy. While we know immunotherapies have historically demonstrated limited efficacy in MSS colorectal cancers, we had hoped to demonstrate meaningful clinical benefit in this patient population and are disappointed in this outcome,” said Jeffrey Walch, M.D., Ph.D., vice president, global program lead, Bristol Myers Squibb. “We continue to be committed to the development of I-O therapies, including Opdivo (nivolumab) and Yervoy (ipilimumab), in MSI-H/dMMR colorectal cancers, and we thank the investigators, patients, and their loved ones who participated in this trial.”
The company will share the data with investigators so they may determine appropriate next steps for patients enrolled in the RELATIVITY-123 trial. The company will complete a full evaluation of the data and work with investigators to share the results with the scientific community.
About RELATIVITY-123
RELATIVITY-123 is a Phase 3 randomized, open label, multi-center trial evaluating the fixed-dose combination of nivolumab and relatlimab compared to regorafenib or trifluridine plus tipiracil (TAS-102) in approximately 700 adult patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC) whose disease has progressed following at least one but no more than four prior lines of therapy for metastatic disease. The study did not include patients with microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) tumors. The dual primary endpoints are overall survival (OS) in all randomized patients and in randomized patients with PD-L1 combined positive score (CPS) ≥ 1. Secondary endpoints include objective response rate (ORR), progression-free survival (PFS), and duration of response (DoR) by Blinded Independent Central Review per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, safety, and time until definitive deterioration-physical function and quality of life in all randomized patients and in randomized patients with PD-L1 CPS ≥ 1.
About LAG-3
Lymphocyte-activation gene 3 (LAG-3) is a cell-surface molecule expressed on effector T cells and regulatory T cells (Tregs) and functions to control T-cell response, activation and growth. LAG-3 inhibits the function of T cells when it interacts with the cell’s ligands and reduces the activation and growth of the cell on which it is found.
This T cell dysfunction allows tumors to avoid attack from the immune system and grow unchecked. Preclinical studies indicate that inhibition of LAG-3 may promote an anti-tumor response. Early research demonstrates that targeting LAG-3 in combination with other potentially complementary immune checkpoints may be a key strategy to more effectively potentiate anti-tumor immune activity.
Bristol Myers Squibb is evaluating relatlimab, its LAG-3-blocking antibody, in clinical trials in combination with other agents in a variety of tumor types.
About Colorectal Cancer
Colorectal cancer (CRC) is cancer that develops in the colon or the rectum, which are part of the body’s digestive or gastrointestinal system. Globally, CRC is the third most commonly diagnosed cancer in the world. In 2020, it is estimated that there were approximately 1,931,000 new cases of the disease and that it will be the second leading cause of cancer-related deaths among men and women combined.
Mismatch repair deficiency (dMMR) occurs when the proteins that repair mismatch errors in DNA replication are missing or non-functional, leading to microsatellite instability-high (MSI-H) tumors. Approximately 5-7% of metastatic CRC patients have dMMR or MSI-H tumors. The remaining 95% of colorectal cancer patients with microsatellite stable (MSS)/proficient mismatch repair (pMMR) tumors have limited treatment options in later-lines of therapy.
Bristol Myers Squibb: Creating a Better Future for People with Cancer
Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine and, through innovative digital platforms, are turning data into insights that sharpen their focus. Deep understanding of causal human biology, cutting-edge capabilities and differentiated research platforms uniquely position the company to approach cancer from every angle.
Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. As a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.
OPDUALAG U.S. INDICATION
Opdualag™ (nivolumab and relatlimab-rmbw) is indicated for the treatment of adult and pediatric patients 12 years of age or older with unresectable or metastatic melanoma.
Please see U.S. Full Prescribing Information for Opdualag.
About the Bristol Myers Squibb and Ono Pharmaceutical Collaboration
In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally, except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol Myers Squibb further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.
About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.
SOURCE: Bristol Myers Squibb
Post Views: 210
