Investigator-assessed objective response rate was 54.8%, responses were durable and median duration of response was not reached
Median overall survival was not reached and overall survival rate at 9-months was 87.6% for patients receiving Opdivo plus Yervoy
PRINCETON, NJ, USA I June 3, 2017 I Bristol-Myers Squibb Company (NYSE:BMY) today announced interim data from CheckMate -142, a Phase 2, multi-cohort trial evaluating Opdivo (nivolumab) monotherapy or in combination with Yervoy (ipilimumab) for the treatment of patients with DNA mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) metastatic colorectal cancer (CRC). These results from the Opdivo and Yervoy combination cohort of the trial included 84 patients who received their first dose at least 6 months prior to analysis. The primary endpoint of investigator-assessed objective response rate (ORR) was 54.8% (95% CI: 43.5, 65.7). Responses were sustained up to 15.9 months and 85% of responses were ongoing; median duration of response was not yet reached. The 9-month overall survival (OS) rate was 87.6% (95% CI: 78.1, 93.1) and median OS had not been reached at the time of analysis. The safety profile of the Opdivo plus Yervoy combination included 28.6% of patients with Grade 3/4 treatment-related adverse events (AEs). These data from Abstract #3531 will be presented today from 8:00–11:30 AM CDT in Hall A at the American Society of Clinical Oncology (ASCO) Annual Meeting 2017.
“The clinically meaningful survival and response data for patients with dMMR or MSI-H colorectal cancer treated with Opdivo in combination with Yervoy are very promising,” said Thierry Andre, M.D., Head of the Medical Oncology Department in St. Antoine Hospital, Assistance Publique Hôpitaux de Paris. “These interim data are important as they build on the study results observed with Opdivo monotherapy in these patients and show the potential of an Immuno-Oncology combination in this advanced type of colorectal cancer for which there is a significant unmet need.”
When the proteins that repair mismatch errors in DNA replication are missing or non-functional, dMMR occurs, and leads to MSI-H tumors in certain types of cancer, including CRC. Approximately 5% of metastatic CRC patients have dMMR or MSI-H biomarkers, and these patients are less likely to benefit from conventional chemotherapy than patients whose tumors are mismatch repair proficient.
“Through our robust Immuno-Oncology research and development efforts, we are investigating predictive biomarkers like dMMR or MSI-H with the goal of tailoring treatment approaches that provide the maximum benefit for individual patients,” said Ian M. Waxman, M.D., development lead, Gastrointestinal Cancers, Bristol-Myers Squibb. “We are encouraged by these interim results for Opdivo plus Yervoy, and we look forward to further evaluating the efficacy and safety of our Immuno-Oncology combination therapies in metastatic colorectal cancer, as well as across a broad range of other tumor types.”
About CheckMate -142 (Abstract #3531)
CheckMate -142 is an international Phase 2, multi-cohort, open-label, non-comparative trial evaluating Opdivo monotherapy or in combination with Yervoy in previously treated recurrent or metastatic colorectal cancer (CRC), including patients with and without DNA mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H). In results from the Opdivo monotherapy cohort presented at the 2017 Gastrointestinal Cancers Symposium, the investigator-assessed objective response rate (ORR) was 31.1% and the 12 month overall survival (OS) rate was 73.8%. In this cohort, Opdivo was well tolerated with a safety profile consistent with that reported in other solid tumors and no new safety signals were observed.
In the combination cohort, the primary endpoint is investigator-assessed ORR using the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Other key endpoints included ORR by blinded independent central review (BICR), progression-free survival (PFS), OS and safety. Patients were treated with Opdivo (3 mg/kg) and Yervoy (1 mg/kg) every three weeks for four doses then Opdivo every two weeks until disease progression, death or unacceptable toxicity. Of the 84 patients treated, 78% had two or more prior lines of therapy.
Treatment-related adverse events (AEs) of any grade occurred in 67.9% of patients. Treatment-related AEs were managed, with 13.1% of patients discontinuing treatment. The most common AEs of any grade occurring in ≥10% of MSI-H patients were diarrhea (23.8%), fatigue (16.7%), aspartate aminotransferase increase (16.7%), pyrexia (15.5%), pruritus (15.5%), alanine aminotransferase increase (14.3%), nausea (14.3%), hyperthyroidism (13.1%) and hypothyroidism (13.1%). Grade 3/4 AEs occurred in 28.6% of patients. No treatment-related deaths were reported.
About Colorectal Cancer and dMMR or MSI-H Colorectal Cancer
Colorectal cancer (CRC) is cancer that develops in the colon or the rectum, which are parts of the body’s digestive or gastrointestinal system. Colorectal cancer is the third most common form of cancer, with a worldwide incidence of 1.4 million cases, and is the fourth most common cause of cancer deaths. In the U.S., CRC is the second leading cause of cancer-related deaths among men and women combined, with more than 135,000 new cases expected to be diagnosed annually.
DNA mismatch repair deficiency (dMMR) occurs when the proteins that repair mismatch errors in DNA replication are missing or non-functional, which leads to microsatellite instability-high (MSI-H) tumors in certain types of cancer, including CRC. Approximately 15% of CRC patients and 5% of metastatic CRC patients have dMMR or MSI-H biomarkers. Patients with dMMR or MSI-H metastatic CRC are less likely to benefit from conventional chemotherapy and typically have a poor prognosis, with lower survival rates on conventional chemotherapy than patients whose tumors are mismatch repair proficient. Routine testing to confirm dMMR or MSI-H status should be conducted for all CRC patients.
Bristol-Myers Squibb & Immuno-Oncology: Advancing Oncology Research
At Bristol-Myers Squibb, patients are at the center of everything we do. Our vision for the future of cancer care is focused on researching and developing transformational Immuno-Oncology (I-O) medicines for hard-to-treat cancers that could potentially improve outcomes for these patients.
We are leading the scientific understanding of I-O through our extensive portfolio of investigational compounds and approved agents. Our differentiated clinical development program is studying broad patient populations across more than 50 types of cancers with 14 clinical-stage molecules designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs position us to advance I-O/I-O, I-O/chemotherapy, I-O/targeted therapies and I-O/radiation therapies across multiple tumors and potentially deliver the next wave of therapies with a sense of urgency. We also continue to pioneer research that will help facilitate a deeper understanding of the role of immune biomarkers and how patients’ individual tumor biology can be used as a guide for treatment decisions throughout their journey.
We understand making the promise of I-O a reality for the many patients who may benefit from these therapies requires not only innovation on our part but also close collaboration with leading experts in the field. Our partnerships with academia, government, advocacy and biotech companies support our collective goal of providing new treatment options to advance the standards of clinical practice.
About Opdivo
Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.
Opdivo’s leading global development program is based on Bristol-Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has enrolled more than 25,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.
In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 60 countries, including the United States, the European Union and Japan. In October 2015, the company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.
U.S. FDA-APPROVED INDICATIONS FOR OPDIVO ®
OPDIVO® (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials
OPDIVO® (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.
OPDIVO® (nivolumab) is indicated for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.
OPDIVO® (nivolumab) is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
About the Bristol-Myers Squibb and Ono Pharmaceutical Co., Ltd. Collaboration
In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Ltd (Ono), 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, Bristol-Myers Squibb and Ono 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 and Facebook.
SOURCE: Bristol-Myers Squibb
Post Views: 90
Investigator-assessed objective response rate was 54.8%, responses were durable and median duration of response was not reached
Median overall survival was not reached and overall survival rate at 9-months was 87.6% for patients receiving Opdivo plus Yervoy
PRINCETON, NJ, USA I June 3, 2017 I Bristol-Myers Squibb Company (NYSE:BMY) today announced interim data from CheckMate -142, a Phase 2, multi-cohort trial evaluating Opdivo (nivolumab) monotherapy or in combination with Yervoy (ipilimumab) for the treatment of patients with DNA mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) metastatic colorectal cancer (CRC). These results from the Opdivo and Yervoy combination cohort of the trial included 84 patients who received their first dose at least 6 months prior to analysis. The primary endpoint of investigator-assessed objective response rate (ORR) was 54.8% (95% CI: 43.5, 65.7). Responses were sustained up to 15.9 months and 85% of responses were ongoing; median duration of response was not yet reached. The 9-month overall survival (OS) rate was 87.6% (95% CI: 78.1, 93.1) and median OS had not been reached at the time of analysis. The safety profile of the Opdivo plus Yervoy combination included 28.6% of patients with Grade 3/4 treatment-related adverse events (AEs). These data from Abstract #3531 will be presented today from 8:00–11:30 AM CDT in Hall A at the American Society of Clinical Oncology (ASCO) Annual Meeting 2017.
“The clinically meaningful survival and response data for patients with dMMR or MSI-H colorectal cancer treated with Opdivo in combination with Yervoy are very promising,” said Thierry Andre, M.D., Head of the Medical Oncology Department in St. Antoine Hospital, Assistance Publique Hôpitaux de Paris. “These interim data are important as they build on the study results observed with Opdivo monotherapy in these patients and show the potential of an Immuno-Oncology combination in this advanced type of colorectal cancer for which there is a significant unmet need.”
When the proteins that repair mismatch errors in DNA replication are missing or non-functional, dMMR occurs, and leads to MSI-H tumors in certain types of cancer, including CRC. Approximately 5% of metastatic CRC patients have dMMR or MSI-H biomarkers, and these patients are less likely to benefit from conventional chemotherapy than patients whose tumors are mismatch repair proficient.
“Through our robust Immuno-Oncology research and development efforts, we are investigating predictive biomarkers like dMMR or MSI-H with the goal of tailoring treatment approaches that provide the maximum benefit for individual patients,” said Ian M. Waxman, M.D., development lead, Gastrointestinal Cancers, Bristol-Myers Squibb. “We are encouraged by these interim results for Opdivo plus Yervoy, and we look forward to further evaluating the efficacy and safety of our Immuno-Oncology combination therapies in metastatic colorectal cancer, as well as across a broad range of other tumor types.”
About CheckMate -142 (Abstract #3531)
CheckMate -142 is an international Phase 2, multi-cohort, open-label, non-comparative trial evaluating Opdivo monotherapy or in combination with Yervoy in previously treated recurrent or metastatic colorectal cancer (CRC), including patients with and without DNA mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H). In results from the Opdivo monotherapy cohort presented at the 2017 Gastrointestinal Cancers Symposium, the investigator-assessed objective response rate (ORR) was 31.1% and the 12 month overall survival (OS) rate was 73.8%. In this cohort, Opdivo was well tolerated with a safety profile consistent with that reported in other solid tumors and no new safety signals were observed.
In the combination cohort, the primary endpoint is investigator-assessed ORR using the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Other key endpoints included ORR by blinded independent central review (BICR), progression-free survival (PFS), OS and safety. Patients were treated with Opdivo (3 mg/kg) and Yervoy (1 mg/kg) every three weeks for four doses then Opdivo every two weeks until disease progression, death or unacceptable toxicity. Of the 84 patients treated, 78% had two or more prior lines of therapy.
Treatment-related adverse events (AEs) of any grade occurred in 67.9% of patients. Treatment-related AEs were managed, with 13.1% of patients discontinuing treatment. The most common AEs of any grade occurring in ≥10% of MSI-H patients were diarrhea (23.8%), fatigue (16.7%), aspartate aminotransferase increase (16.7%), pyrexia (15.5%), pruritus (15.5%), alanine aminotransferase increase (14.3%), nausea (14.3%), hyperthyroidism (13.1%) and hypothyroidism (13.1%). Grade 3/4 AEs occurred in 28.6% of patients. No treatment-related deaths were reported.
About Colorectal Cancer and dMMR or MSI-H Colorectal Cancer
Colorectal cancer (CRC) is cancer that develops in the colon or the rectum, which are parts of the body’s digestive or gastrointestinal system. Colorectal cancer is the third most common form of cancer, with a worldwide incidence of 1.4 million cases, and is the fourth most common cause of cancer deaths. In the U.S., CRC is the second leading cause of cancer-related deaths among men and women combined, with more than 135,000 new cases expected to be diagnosed annually.
DNA mismatch repair deficiency (dMMR) occurs when the proteins that repair mismatch errors in DNA replication are missing or non-functional, which leads to microsatellite instability-high (MSI-H) tumors in certain types of cancer, including CRC. Approximately 15% of CRC patients and 5% of metastatic CRC patients have dMMR or MSI-H biomarkers. Patients with dMMR or MSI-H metastatic CRC are less likely to benefit from conventional chemotherapy and typically have a poor prognosis, with lower survival rates on conventional chemotherapy than patients whose tumors are mismatch repair proficient. Routine testing to confirm dMMR or MSI-H status should be conducted for all CRC patients.
Bristol-Myers Squibb & Immuno-Oncology: Advancing Oncology Research
At Bristol-Myers Squibb, patients are at the center of everything we do. Our vision for the future of cancer care is focused on researching and developing transformational Immuno-Oncology (I-O) medicines for hard-to-treat cancers that could potentially improve outcomes for these patients.
We are leading the scientific understanding of I-O through our extensive portfolio of investigational compounds and approved agents. Our differentiated clinical development program is studying broad patient populations across more than 50 types of cancers with 14 clinical-stage molecules designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs position us to advance I-O/I-O, I-O/chemotherapy, I-O/targeted therapies and I-O/radiation therapies across multiple tumors and potentially deliver the next wave of therapies with a sense of urgency. We also continue to pioneer research that will help facilitate a deeper understanding of the role of immune biomarkers and how patients’ individual tumor biology can be used as a guide for treatment decisions throughout their journey.
We understand making the promise of I-O a reality for the many patients who may benefit from these therapies requires not only innovation on our part but also close collaboration with leading experts in the field. Our partnerships with academia, government, advocacy and biotech companies support our collective goal of providing new treatment options to advance the standards of clinical practice.
About Opdivo
Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.
Opdivo’s leading global development program is based on Bristol-Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has enrolled more than 25,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.
In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 60 countries, including the United States, the European Union and Japan. In October 2015, the company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.
U.S. FDA-APPROVED INDICATIONS FOR OPDIVO ®
OPDIVO® (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials
OPDIVO® (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.
OPDIVO® (nivolumab) is indicated for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.
OPDIVO® (nivolumab) is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
About the Bristol-Myers Squibb and Ono Pharmaceutical Co., Ltd. Collaboration
In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Ltd (Ono), 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, Bristol-Myers Squibb and Ono 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 and Facebook.
SOURCE: Bristol-Myers Squibb
Post Views: 90
