First and only PD-1 inhibitor approved for a hematologic malignancy in the European Union
Approval based on an overall response rate, as demonstrated by data from an integrated analysis of two trials, CheckMate -205 and CheckMate -039
This milestone marks the sixth EU approval for Opdivo in four distinct cancer types in less than two years
The approval is based on an integrated analysis of data from the Phase 2 CheckMate -205 and the Phase 1 CheckMate -039 trials, evaluating patients with relapsed or refractory cHL after ASCT and treatment with brentuximab vedotin. In the subset of patients in the efficacy population (n=95), the primary endpoint of objective response rate (ORR) as assessed by an independent radiologic review committee was 66% (95% CI: 56-76; 63/95 patients). The percentage of patients with a complete response was 6% (95% CI: 2-13; 6/95 patients), and the percentage of patients with a partial response was 60% (95% CI: 49-70; 57/95 patients). At 12 months, the progression-free survival rate was 57% (95% CI: 45-68). Opdivo is associated with warnings and precautions including immune-related: pneumonitis, colitis, hepatitis, nephritis and renal dysfunction, endocrinopathies, rash, and other adverse reactions; infusion reactions, and complications of allogeneic hematopoietic stem cell transplantation (HSCT) in cHL after Opdivo.
Emmanuel Blin, senior vice president and chief strategy officer, Bristol-Myers Squibb, commented, “We’re incredibly proud of this approval for Opdivo and what it means for adult patients with relapsed or refractory classical Hodgkin lymphoma after autologous stem cell transplant and treatment with brentuximab vedotin, as it marks the first and only PD-1 inhibitor approved for a hematologic malignancy in the EU. This also is Bristol-Myers Squibb’s second Immuno-Oncology agent approved for a blood cancer in the EU within just six months.”
“As a practicing hematologist, I have experienced the challenge of managing classical Hodgkin lymphoma and the need among previously treated patients,” said Andreas Engert, M.D., lead investigator and professor of Internal Medicine, Hematology and Oncology, University Hospital of Cologne, Cologne, Germany. “It is incredibly exciting that with today’s approval of Opdivo for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma after autologous stem cell transplant and treatment with brentuximab vedotin in the EU, we now have an entirely new treatment approach that has shown impressive response rates and durability of response in this difficult-to-treat population.”
In the integrated analysis of data from CheckMate -205 and CheckMate -039, the median time to response was 2.0 months (range 0.7-11.1), and among responders, the duration of response was maintained over time for a median of 13.1 months (95% CI: 9.5-NE; range 0.0+, 23.1+). Stable disease was observed in 23% of patients. In a post-hoc analysis of the 80 patients in CheckMate -205 cohort B, it was found 37 patients had no response to prior brentuximab vedotin treatment. Among these 37 patients, treatment with Opdivo resulted in an ORR of 59.5% (22/37), and the median duration of response was 13.14 months.
The safety of Opdivo in cHL was evaluated in 263 adult patients from CheckMate -205 (n=240) and CheckMate -039 (n=23). Among these patients (total safety population: n=263), serious adverse events (AEs) occurred in 21% of patients. The most common serious AEs (reported in at least 1% of patients) were infusion-related reaction, pneumonia, pleural effusion, pyrexia, rash and pneumonitis. The most common AEs (reported in at least 20% of patients) were fatigue (32%), upper respiratory tract infection (28%), pyrexia (24%), diarrhea (23%), and cough (22%). Twenty-three percent of patients had a dose delay for an AE, and 4.2% of patients discontinued treatment due to AEs. Six out of 40 patients died from complications of allogeneic HSCT after Opdivo, and these 40 patients had a median follow-up from subsequent allogeneic HSCT of 2.9 months (range: 0-22).
About Classical Hodgkin Lymphoma
Hodgkin lymphoma (HL), also known as Hodgkin disease, is a cancer that starts in white blood cells called lymphocytes, which are part of the body’s immune system. In the European Union, about 12,200 new cases and 2,600 deaths occurred in 2012 as a result of HL. The disease is most often diagnosed in early adulthood (ages 20-40) and late adulthood (older than 55 years of age). Classical Hodgkin lymphoma is the most common type of HL, accounting for 95% of cases.
Bristol-Myers Squibb: At the Forefront of Immuno-Oncology Science & Innovation
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 + Yervoy combination 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 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: 43
First and only PD-1 inhibitor approved for a hematologic malignancy in the European Union
Approval based on an overall response rate, as demonstrated by data from an integrated analysis of two trials, CheckMate -205 and CheckMate -039
This milestone marks the sixth EU approval for Opdivo in four distinct cancer types in less than two years
The approval is based on an integrated analysis of data from the Phase 2 CheckMate -205 and the Phase 1 CheckMate -039 trials, evaluating patients with relapsed or refractory cHL after ASCT and treatment with brentuximab vedotin. In the subset of patients in the efficacy population (n=95), the primary endpoint of objective response rate (ORR) as assessed by an independent radiologic review committee was 66% (95% CI: 56-76; 63/95 patients). The percentage of patients with a complete response was 6% (95% CI: 2-13; 6/95 patients), and the percentage of patients with a partial response was 60% (95% CI: 49-70; 57/95 patients). At 12 months, the progression-free survival rate was 57% (95% CI: 45-68). Opdivo is associated with warnings and precautions including immune-related: pneumonitis, colitis, hepatitis, nephritis and renal dysfunction, endocrinopathies, rash, and other adverse reactions; infusion reactions, and complications of allogeneic hematopoietic stem cell transplantation (HSCT) in cHL after Opdivo.
Emmanuel Blin, senior vice president and chief strategy officer, Bristol-Myers Squibb, commented, “We’re incredibly proud of this approval for Opdivo and what it means for adult patients with relapsed or refractory classical Hodgkin lymphoma after autologous stem cell transplant and treatment with brentuximab vedotin, as it marks the first and only PD-1 inhibitor approved for a hematologic malignancy in the EU. This also is Bristol-Myers Squibb’s second Immuno-Oncology agent approved for a blood cancer in the EU within just six months.”
“As a practicing hematologist, I have experienced the challenge of managing classical Hodgkin lymphoma and the need among previously treated patients,” said Andreas Engert, M.D., lead investigator and professor of Internal Medicine, Hematology and Oncology, University Hospital of Cologne, Cologne, Germany. “It is incredibly exciting that with today’s approval of Opdivo for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma after autologous stem cell transplant and treatment with brentuximab vedotin in the EU, we now have an entirely new treatment approach that has shown impressive response rates and durability of response in this difficult-to-treat population.”
In the integrated analysis of data from CheckMate -205 and CheckMate -039, the median time to response was 2.0 months (range 0.7-11.1), and among responders, the duration of response was maintained over time for a median of 13.1 months (95% CI: 9.5-NE; range 0.0+, 23.1+). Stable disease was observed in 23% of patients. In a post-hoc analysis of the 80 patients in CheckMate -205 cohort B, it was found 37 patients had no response to prior brentuximab vedotin treatment. Among these 37 patients, treatment with Opdivo resulted in an ORR of 59.5% (22/37), and the median duration of response was 13.14 months.
The safety of Opdivo in cHL was evaluated in 263 adult patients from CheckMate -205 (n=240) and CheckMate -039 (n=23). Among these patients (total safety population: n=263), serious adverse events (AEs) occurred in 21% of patients. The most common serious AEs (reported in at least 1% of patients) were infusion-related reaction, pneumonia, pleural effusion, pyrexia, rash and pneumonitis. The most common AEs (reported in at least 20% of patients) were fatigue (32%), upper respiratory tract infection (28%), pyrexia (24%), diarrhea (23%), and cough (22%). Twenty-three percent of patients had a dose delay for an AE, and 4.2% of patients discontinued treatment due to AEs. Six out of 40 patients died from complications of allogeneic HSCT after Opdivo, and these 40 patients had a median follow-up from subsequent allogeneic HSCT of 2.9 months (range: 0-22).
About Classical Hodgkin Lymphoma
Hodgkin lymphoma (HL), also known as Hodgkin disease, is a cancer that starts in white blood cells called lymphocytes, which are part of the body’s immune system. In the European Union, about 12,200 new cases and 2,600 deaths occurred in 2012 as a result of HL. The disease is most often diagnosed in early adulthood (ages 20-40) and late adulthood (older than 55 years of age). Classical Hodgkin lymphoma is the most common type of HL, accounting for 95% of cases.
Bristol-Myers Squibb: At the Forefront of Immuno-Oncology Science & Innovation
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 + Yervoy combination 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 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: 43
