Overall response rate with Opdivo was 21%, and more than double with the Opdivo plus Yervoy combination (46%), in patients with high tumor mutation burden
Overall survival rate with Opdivo at one year was 35%, and nearly double with the Opdivo plus Yervoy combination (62%), in patients with high tumor mutation burden
First report of tumor mutation burden as a potential predictive biomarker for the combination of two I-O agents
PRINCETON, NJ, USA I October 16, 2017 I Bristol-Myers Squibb Company (NYSE:BMY) today announced data evaluating Opdivo (nivolumab) and Opdivo plus Yervoy (ipilimumab) in previously treated small cell lung cancer (SCLC) patients whose tumors were evaluable for tumor mutation burden (TMB), from the Phase 1/2 CheckMate -032 trial. The primary objective of this trial was objective response rate (ORR) as assessed by a blinded independent central review (BICR), for which results were previously presented; in the pooled intent-to-treat (ITT) population (n=401), the ORR was 11% with Opdivo alone and 22% with the combination. Among the ITT population, 211 (53%) patients had an evaluable TMB result for these analyses and were divided into subgroups of high, medium and low levels of TMB.
Patients with high TMB who received Opdivo plus Yervoy had an ORR of 46%; the ORR was 16% and 22% in patients with medium and low levels of TMB, respectively. Patients with high TMB who received Opdivo had an ORR of 21%; the ORR was 7% and 5%, in patients with medium and low levels of TMB, respectively. In patients with high TMB who received Opdivo plus Yervoy, 62% were alive at one year; 20% and 23% of patients with medium and low levels of TMB were alive at one year, respectively. In patients with high TMB who received Opdivo, 35% were alive at one year; 26% and 22% of patients with medium and low levels of TMB were alive at one year, respectively. No new safety data were presented in this analysis.
Over time, cancer cells accumulate mutations that are not seen in normal cells of the body. Tumor mutation burden is a measurement of the quantity of mutations carried by tumor cells, and is one type of biomarker that may help predict the likelihood a patient responds to Immuno-Oncology (I-O) therapies.
“These exploratory TMB data from CheckMate -032 are the first to show the potential of using mutation burden to predict response in some patients with the combination of two I-O agents,” said Matthew D. Hellmann, M.D., study investigator, Memorial Sloan Kettering Cancer Center. “Further investigation is warranted to explore the application of this marker across lung cancers, and in the setting of both I-O combination and monotherapy.”
These data will be presented today at the International Association for the Study of Lung Cancer (IASLC) 18th World Conference on Lung Cancer (WCLC) in Yokohama, Japan during the Biomarker for Lung Cancer oral session from 4:15-4:25 PM JST (Abstract # 11063).
Nick Botwood, M.D., development lead, thoracic cancers, Bristol-Myers Squibb, said, “Assessing the effect of TMB on treatment outcomes has been an important part of our ongoing translational medicine research. Based on these exploratory data from CheckMate -032 in previously treated small cell lung cancer, and the growing scientific evidence for this biomarker, we continue to investigate TMB to understand its relevance as a marker to potentially predict outcomes with immunotherapy. We are committed to our ongoing thoracic cancer development program, focused on identifying patients most likely to benefit from immunotherapy.”
About CheckMate -032
CheckMate -032 is an ongoing Phase 1/2 open-label trial, evaluating the safety and efficacy of Opdivo monotherapy 3 mg/kg every two weeks or Opdivo 1 mg/kg plus Yervoy 3 mg/kg every three weeks for four cycles, in advanced or metastatic solid tumors. All patients were treated until disease progression or unacceptable toxicity. The trial included both PD-L1 expressors and non-expressors. The primary objective was objective response rate (ORR) as assessed by a blinded independent central review (BICR). Secondary objectives included safety, overall survival (OS), progression-free survival (PFS) and duration of response (DOR). Biomarker analysis was an exploratory objective.
Progression-free survival data for the TMB-evaluable patient population were also presented at the WCLC. Patients with high TMB who received Opdivo plus Yervoy had a one-year PFS rate of 30%; the rates were 8% and 6% in patients with medium and low TMB levels, respectively. Patients with high TMB who received Opdivo had a one-year PFS rate of 21%; the rate was 3% in patients with medium TMB level; PFS was not evaluable in patents with low TMB level.
About Small Cell Lung Cancer
Small cell lung cancer (SCLC) is one of two main types of lung cancer, which has been the most common cancer in the world for several decades and accounts for about 10% to 15% of all lung cancers. Survival rates vary depending on the stage of the cancer when it is diagnosed, and five-year survival rates tend to be lower than non-small cell lung cancer, as SCLC is faster growing and symptoms are often not detected until the cancer is at an advanced stage. Globally, the five-year survival rate for Stage I SCLC is between 20% and 40%; for Stage IV SCLC, the five-year survival rate drops to 1%.
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’ 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.
OPDIVO® (nivolumab) is indicated for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. 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 hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the 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.
About the WCLC
The World Conference on Lung Cancer (WCLC) is the world’s largest meeting dedicated to lung cancer and other thoracic malignancies, attracting over 6,000 researchers, physicians and specialists from more than 100 countries. The goal is to disseminate the latest scientific achievements; increase awareness, collaboration and understanding of lung cancer; and to help participants implement the latest developments across the globe. Organized under the theme of “Synergy to Conquer Lung Cancer,” the conference will cover a wide range of disciplines and unveil several research studies and clinical trial results. For more information, visit http://wclc2017.iaslc.org/.
SOURCE: Bristol-Myers Squibb
Post Views: 9
Overall response rate with Opdivo was 21%, and more than double with the Opdivo plus Yervoy combination (46%), in patients with high tumor mutation burden
Overall survival rate with Opdivo at one year was 35%, and nearly double with the Opdivo plus Yervoy combination (62%), in patients with high tumor mutation burden
First report of tumor mutation burden as a potential predictive biomarker for the combination of two I-O agents
PRINCETON, NJ, USA I October 16, 2017 I Bristol-Myers Squibb Company (NYSE:BMY) today announced data evaluating Opdivo (nivolumab) and Opdivo plus Yervoy (ipilimumab) in previously treated small cell lung cancer (SCLC) patients whose tumors were evaluable for tumor mutation burden (TMB), from the Phase 1/2 CheckMate -032 trial. The primary objective of this trial was objective response rate (ORR) as assessed by a blinded independent central review (BICR), for which results were previously presented; in the pooled intent-to-treat (ITT) population (n=401), the ORR was 11% with Opdivo alone and 22% with the combination. Among the ITT population, 211 (53%) patients had an evaluable TMB result for these analyses and were divided into subgroups of high, medium and low levels of TMB.
Patients with high TMB who received Opdivo plus Yervoy had an ORR of 46%; the ORR was 16% and 22% in patients with medium and low levels of TMB, respectively. Patients with high TMB who received Opdivo had an ORR of 21%; the ORR was 7% and 5%, in patients with medium and low levels of TMB, respectively. In patients with high TMB who received Opdivo plus Yervoy, 62% were alive at one year; 20% and 23% of patients with medium and low levels of TMB were alive at one year, respectively. In patients with high TMB who received Opdivo, 35% were alive at one year; 26% and 22% of patients with medium and low levels of TMB were alive at one year, respectively. No new safety data were presented in this analysis.
Over time, cancer cells accumulate mutations that are not seen in normal cells of the body. Tumor mutation burden is a measurement of the quantity of mutations carried by tumor cells, and is one type of biomarker that may help predict the likelihood a patient responds to Immuno-Oncology (I-O) therapies.
“These exploratory TMB data from CheckMate -032 are the first to show the potential of using mutation burden to predict response in some patients with the combination of two I-O agents,” said Matthew D. Hellmann, M.D., study investigator, Memorial Sloan Kettering Cancer Center. “Further investigation is warranted to explore the application of this marker across lung cancers, and in the setting of both I-O combination and monotherapy.”
These data will be presented today at the International Association for the Study of Lung Cancer (IASLC) 18th World Conference on Lung Cancer (WCLC) in Yokohama, Japan during the Biomarker for Lung Cancer oral session from 4:15-4:25 PM JST (Abstract # 11063).
Nick Botwood, M.D., development lead, thoracic cancers, Bristol-Myers Squibb, said, “Assessing the effect of TMB on treatment outcomes has been an important part of our ongoing translational medicine research. Based on these exploratory data from CheckMate -032 in previously treated small cell lung cancer, and the growing scientific evidence for this biomarker, we continue to investigate TMB to understand its relevance as a marker to potentially predict outcomes with immunotherapy. We are committed to our ongoing thoracic cancer development program, focused on identifying patients most likely to benefit from immunotherapy.”
About CheckMate -032
CheckMate -032 is an ongoing Phase 1/2 open-label trial, evaluating the safety and efficacy of Opdivo monotherapy 3 mg/kg every two weeks or Opdivo 1 mg/kg plus Yervoy 3 mg/kg every three weeks for four cycles, in advanced or metastatic solid tumors. All patients were treated until disease progression or unacceptable toxicity. The trial included both PD-L1 expressors and non-expressors. The primary objective was objective response rate (ORR) as assessed by a blinded independent central review (BICR). Secondary objectives included safety, overall survival (OS), progression-free survival (PFS) and duration of response (DOR). Biomarker analysis was an exploratory objective.
Progression-free survival data for the TMB-evaluable patient population were also presented at the WCLC. Patients with high TMB who received Opdivo plus Yervoy had a one-year PFS rate of 30%; the rates were 8% and 6% in patients with medium and low TMB levels, respectively. Patients with high TMB who received Opdivo had a one-year PFS rate of 21%; the rate was 3% in patients with medium TMB level; PFS was not evaluable in patents with low TMB level.
About Small Cell Lung Cancer
Small cell lung cancer (SCLC) is one of two main types of lung cancer, which has been the most common cancer in the world for several decades and accounts for about 10% to 15% of all lung cancers. Survival rates vary depending on the stage of the cancer when it is diagnosed, and five-year survival rates tend to be lower than non-small cell lung cancer, as SCLC is faster growing and symptoms are often not detected until the cancer is at an advanced stage. Globally, the five-year survival rate for Stage I SCLC is between 20% and 40%; for Stage IV SCLC, the five-year survival rate drops to 1%.
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’ 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.
OPDIVO® (nivolumab) is indicated for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. 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 hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the 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.
About the WCLC
The World Conference on Lung Cancer (WCLC) is the world’s largest meeting dedicated to lung cancer and other thoracic malignancies, attracting over 6,000 researchers, physicians and specialists from more than 100 countries. The goal is to disseminate the latest scientific achievements; increase awareness, collaboration and understanding of lung cancer; and to help participants implement the latest developments across the globe. Organized under the theme of “Synergy to Conquer Lung Cancer,” the conference will cover a wide range of disciplines and unveil several research studies and clinical trial results. For more information, visit http://wclc2017.iaslc.org/.
SOURCE: Bristol-Myers Squibb
Post Views: 9
