Objective response rate with Opdivo plus Yervoy was 25% and was 11% with Opdivo monotherapy; in the combination arm, three patients experienced a complete response
Estimated two-year survival rate with the combination was 30% and was 17% with Opdivo monotherapy
No new safety signals were observed with Opdivo and Opdivo plus Yervoy in this updated analysis
PRINCETON, NJ, USA I December 6, 2016 I Bristol-Myers Squibb Company (NYSE:BMY) announced today updated results for Opdivo monotherapy (3 mg/kg every two weeks [n=98]) and in combination with Yervoy (Opdivo 1 mg/kg plus Yervoy 3 mg/kg every three weeks [n=61]) in previously treated small cell lung cancer (SCLC) patients, a cohort of the Phase 1/2 open-label CheckMate -032 trial. The confirmed objective response rate (primary objective) was 25% (95% CI: 15, 37) in patients who received Opdivo plus Yervoy and was 11% (95% CI: 6, 19) with Opdivo alone with additional follow-up. Response was observed regardless of platinum sensitivity or prior lines of therapy. With the combination, three patients experienced a complete response. The estimated two-year overall survival rate (secondary objective) was 30% with Opdivo plus Yervoy and was 17% with Opdivo alone. In this updated analysis, no new safety signals were observed. Grade 3/4 treatment-related discontinuation rates were 10% in the Opdivo plus Yervoy group and 4% in the Opdivo group.
“Small cell lung cancer is a highly aggressive, rapidly progressive disease with most patients relapsing within a year of diagnosis. There have been no significant changes in systemic treatment options in the last 30 years,” said Matthew D. Hellmann, M.D., study investigator, Memorial Sloan Kettering Cancer Center. “In the CheckMate -032 trial, we observed that responses occurred in a quarter of patients with small cell lung cancer treated with the combination of nivolumab and ipilimumab. Responses were associated with promising survival, including 30% of these patients alive at two years after beginning treatment with the combination. These data offer important new information in the study of nivolumab plus ipilimumab as a potential treatment option for some patients with small cell lung cancer.”
These results will be presented today at the International Association for the Study of Lung Cancer 17th World Conference on Lung Cancer in Vienna, Austria, during a Mini Oral Session at 2:45-2:51 p.m. CET.
Nick Botwood, M.D., development lead, Lung, Bristol-Myers Squibb commented, “In the small cell lung cancer cohort of CheckMate -032, we observed promising response and survival rates when Yervoy is added to Opdivo. We find these results encouraging, and through our broad lung development program, are committed to further investigating Opdivo as monotherapy and in combination with Yervoy for small cell lung cancer patients in two ongoing Phase 3 trials.”
About CheckMate -032
CheckMate -032 is an ongoing Phase 1/2 open-label trial, evaluating the safety and efficacy of Opdivo monotherapy, or Opdivo combined with Yervoy, in advanced or metastatic solid tumors at different doses and schedules. The trial included both PD-L1 expressors and non-expressors. The primary objective was investigator-assessed confirmed objective response rate (ORR) per RECIST version 1.1. Secondary objectives included safety, overall survival (OS), progression-free survival (PFS) and duration of response (DOR). Biomarker analysis was an exploratory objective.
The CheckMate -032 small cell lung cancer (SCLC) cohort included 217 patients with progressive disease after one or more prior lines of therapy, including a first-line platinum-based chemotherapy regimen. In this analysis, patients received Opdivo monotherapy 3 mg/kg administered intravenously every two weeks or Opdivo 1 mg/kg plus Yervoy 3 mg/kg every three weeks for four cycles, followed by Opdivo 3 mg/kg every two weeks. All patients were treated until disease progression or unacceptable toxicity. Patients were followed for a median of 21 months in the combination cohort and 15.7 months in the Opdivo monotherapy cohort. Across cohorts, 73% were evaluable for PD-L1 expression at baseline; 17% (of PD-L1 evaluable samples) had ≥1% tumor PD-L1 expression.
In addition to the survival and response data reported, additional efficacy findings included confirmed partial response in 21 patients in the Opdivo and Yervoy combination arm and 11 patients in the Opdivo-only arm. Confirmed stable disease was consistent across both treatment arms (25 patients in combination arm; 24 patients in monotherapy arm). Median DOR was 11.7 months in the combination group (95% CI: 4.0, NR); DOR was not reached in the monotherapy group. In the combination and monotherapy arms, respectively, 33% (5/15) and 27% (3/11) of responders had ongoing responses lasting approximately >18 months after treatment initiation.
The most commonly reported Grade 3/4 treatment-related adverse events (AE) in ≥10% of patients on the monotherapy and combination arms, respectively, were fatigue (1%, 0%), pruitius (0%, 2%), diarrhea (0%, 5%), nausea (0%, 2%), rash (0%, 5%), hypothyroidism (0%, 2%), maculopapular rash (0%, 3%) and increased lipase (0%, 8%). In the Opdivo-only group 4% of patients discontinued treatment due to Grade 3/4 treatment-related AEs, and 10% in the combination group. No additional treatment-related deaths were reported. At prior disclosure, two treatment related deaths occurred with the combination (myasthenia gravis and worsening of renal failure). Grade 3/4 treatment-related limbic encephalitis occurred in 1 patient in the monotherapy group. Treatment-related pneumonitis occurred in 4 patients in the monotherapy group (two Grade 3/4 events) and 1 patient in the combination group (one Grade 3/4 event).
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 10-15% 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 that will raise survival expectations in hard-to-treat cancers and will change the way patients live with cancer.
We are leading the scientific understanding of I-O through our extensive portfolio of investigational and approved agents, including the first combination of two I-O agents in metastatic melanoma, and our differentiated clinical development program, which is studying broad patient populations across more than 20 types of cancers with 11 clinical-stage molecules designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs uniquely position us to advance the science of combinations across multiple tumors and potentially deliver the next wave of I-O combination regimens 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 inform which patients will benefit most from I-O therapies.
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 57 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 47 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 patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin. 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.
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: 41
Objective response rate with Opdivo plus Yervoy was 25% and was 11% with Opdivo monotherapy; in the combination arm, three patients experienced a complete response
Estimated two-year survival rate with the combination was 30% and was 17% with Opdivo monotherapy
No new safety signals were observed with Opdivo and Opdivo plus Yervoy in this updated analysis
PRINCETON, NJ, USA I December 6, 2016 I Bristol-Myers Squibb Company (NYSE:BMY) announced today updated results for Opdivo monotherapy (3 mg/kg every two weeks [n=98]) and in combination with Yervoy (Opdivo 1 mg/kg plus Yervoy 3 mg/kg every three weeks [n=61]) in previously treated small cell lung cancer (SCLC) patients, a cohort of the Phase 1/2 open-label CheckMate -032 trial. The confirmed objective response rate (primary objective) was 25% (95% CI: 15, 37) in patients who received Opdivo plus Yervoy and was 11% (95% CI: 6, 19) with Opdivo alone with additional follow-up. Response was observed regardless of platinum sensitivity or prior lines of therapy. With the combination, three patients experienced a complete response. The estimated two-year overall survival rate (secondary objective) was 30% with Opdivo plus Yervoy and was 17% with Opdivo alone. In this updated analysis, no new safety signals were observed. Grade 3/4 treatment-related discontinuation rates were 10% in the Opdivo plus Yervoy group and 4% in the Opdivo group.
“Small cell lung cancer is a highly aggressive, rapidly progressive disease with most patients relapsing within a year of diagnosis. There have been no significant changes in systemic treatment options in the last 30 years,” said Matthew D. Hellmann, M.D., study investigator, Memorial Sloan Kettering Cancer Center. “In the CheckMate -032 trial, we observed that responses occurred in a quarter of patients with small cell lung cancer treated with the combination of nivolumab and ipilimumab. Responses were associated with promising survival, including 30% of these patients alive at two years after beginning treatment with the combination. These data offer important new information in the study of nivolumab plus ipilimumab as a potential treatment option for some patients with small cell lung cancer.”
These results will be presented today at the International Association for the Study of Lung Cancer 17th World Conference on Lung Cancer in Vienna, Austria, during a Mini Oral Session at 2:45-2:51 p.m. CET.
Nick Botwood, M.D., development lead, Lung, Bristol-Myers Squibb commented, “In the small cell lung cancer cohort of CheckMate -032, we observed promising response and survival rates when Yervoy is added to Opdivo. We find these results encouraging, and through our broad lung development program, are committed to further investigating Opdivo as monotherapy and in combination with Yervoy for small cell lung cancer patients in two ongoing Phase 3 trials.”
About CheckMate -032
CheckMate -032 is an ongoing Phase 1/2 open-label trial, evaluating the safety and efficacy of Opdivo monotherapy, or Opdivo combined with Yervoy, in advanced or metastatic solid tumors at different doses and schedules. The trial included both PD-L1 expressors and non-expressors. The primary objective was investigator-assessed confirmed objective response rate (ORR) per RECIST version 1.1. Secondary objectives included safety, overall survival (OS), progression-free survival (PFS) and duration of response (DOR). Biomarker analysis was an exploratory objective.
The CheckMate -032 small cell lung cancer (SCLC) cohort included 217 patients with progressive disease after one or more prior lines of therapy, including a first-line platinum-based chemotherapy regimen. In this analysis, patients received Opdivo monotherapy 3 mg/kg administered intravenously every two weeks or Opdivo 1 mg/kg plus Yervoy 3 mg/kg every three weeks for four cycles, followed by Opdivo 3 mg/kg every two weeks. All patients were treated until disease progression or unacceptable toxicity. Patients were followed for a median of 21 months in the combination cohort and 15.7 months in the Opdivo monotherapy cohort. Across cohorts, 73% were evaluable for PD-L1 expression at baseline; 17% (of PD-L1 evaluable samples) had ≥1% tumor PD-L1 expression.
In addition to the survival and response data reported, additional efficacy findings included confirmed partial response in 21 patients in the Opdivo and Yervoy combination arm and 11 patients in the Opdivo-only arm. Confirmed stable disease was consistent across both treatment arms (25 patients in combination arm; 24 patients in monotherapy arm). Median DOR was 11.7 months in the combination group (95% CI: 4.0, NR); DOR was not reached in the monotherapy group. In the combination and monotherapy arms, respectively, 33% (5/15) and 27% (3/11) of responders had ongoing responses lasting approximately >18 months after treatment initiation.
The most commonly reported Grade 3/4 treatment-related adverse events (AE) in ≥10% of patients on the monotherapy and combination arms, respectively, were fatigue (1%, 0%), pruitius (0%, 2%), diarrhea (0%, 5%), nausea (0%, 2%), rash (0%, 5%), hypothyroidism (0%, 2%), maculopapular rash (0%, 3%) and increased lipase (0%, 8%). In the Opdivo-only group 4% of patients discontinued treatment due to Grade 3/4 treatment-related AEs, and 10% in the combination group. No additional treatment-related deaths were reported. At prior disclosure, two treatment related deaths occurred with the combination (myasthenia gravis and worsening of renal failure). Grade 3/4 treatment-related limbic encephalitis occurred in 1 patient in the monotherapy group. Treatment-related pneumonitis occurred in 4 patients in the monotherapy group (two Grade 3/4 events) and 1 patient in the combination group (one Grade 3/4 event).
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 10-15% 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 that will raise survival expectations in hard-to-treat cancers and will change the way patients live with cancer.
We are leading the scientific understanding of I-O through our extensive portfolio of investigational and approved agents, including the first combination of two I-O agents in metastatic melanoma, and our differentiated clinical development program, which is studying broad patient populations across more than 20 types of cancers with 11 clinical-stage molecules designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs uniquely position us to advance the science of combinations across multiple tumors and potentially deliver the next wave of I-O combination regimens 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 inform which patients will benefit most from I-O therapies.
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 57 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 47 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 patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin. 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.
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: 41
