Phase 1/2a data demonstrate encouraging activity of anti-LAG-3 (BMS-986016) and Opdivo combination in heavily pretreated advanced melanoma patients who were relapsed or refractory on anti-PD-1/PD-L1 therapy
Analyses suggest LAG-3 biomarker may be promising to identify patients who are more likely to benefit from this therapeutic combination
Combination of two checkpoint inhibitors had a similar safety profile to Opdivo monotherapy
PRINCETON, NJ, USA I June 3, 2017 I Bristol-Myers Squibb Company (NYSE:BMY) today announced proof-of-concept data showing preliminary efficacy for BMS-986016, an investigational anti-lymphocyte-activation gene 3 (LAG-3) therapy in combination with Opdivo (nivolumab) in patients with advanced melanoma previously treated with anti-PD-1/PD-L1 therapy (n=55). In the ongoing expansion study of heavily pretreated patients who were refractory to or relapsed on anti-PD1/PDL1 therapy, the objective response rate (ORR) was 12.5 percent in evaluable patients (n=48). Patients with LAG-3 expression in at least 1 percent (n=25) of tumor-associated immune cells within the tumor margin had a nearly three-fold improvement in ORR compared to patients with less than 1 percent LAG-3 expression (n=14) (20 percent and 7.1 percent, respectively). These data will be presented today, Saturday, June 3, at the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO) in a poster from 1:15 p.m. – 4:45 p.m. CDT and poster discussion from 4:45 p.m. – 6 p.m. CDT (Abstract #9520).
For some tumor types, immunotherapy is becoming a standard of care, but there are growing numbers of patients who are refractory to or relapse on anti-PD-1/PD-L1 therapy and these patients typically have poor outcomes. These proof-of-concept data show that combining anti-LAG-3 with Opdivo in PD-1/PD-L1 refractory patients may help patients overcome resistance and restore T cell function.
“As a potentially synergistic immune pathway to PD-1/PD-L1, LAG-3 has emerged as an immune checkpoint receptor that regulates T cell function and whose inhibition may increase benefits for patients,” said Paolo Ascierto, M.D., Istituto Nazionale Tumori Fondazione Pascale of Naples, Italy. “These results indicate that BMS-986016 in combination with Opdivo may offer clinical benefit, particularly for patients whose tumors contain immune cells that express LAG-3. Further investigation is warranted to understand the impact of this combination as well as the utility of LAG-3 as an immune biomarker.”
“Advances in immunotherapy have been transformational for many cancer patients, but unfortunately some patients do not respond well or even relapse after an initial response to treatment,” said Fouad Namouni, M.D. head of Oncology Development, Bristol-Myers Squibb. “Across our portfolio, we are actively working to characterize the underlying biology for anti-PD-1/PD-L1 resistant tumors and to determine predictive biomarkers to inform rational treatment combinations. We are very encouraged by these results demonstrating a potential role for anti-LAG3 in this setting and look forward to the ongoing broader investigation of LAG-3 as an alternative therapeutic target and predictive biomarker.”
Bristol-Myers Squibb is developing an oncology pipeline of more than 21 clinical agents with a range of mechanisms and translational approaches, applying evidence-based scientific understanding of the complex and multifactorial immune system.
About the Study
CA224-020 is a Phase 1/2a open label, dose escalation and cohort expansion study of the safety, tolerability and efficacy of an anti-LAG-3 monoclonal antibody in combination with Opdivo in advanced solid tumors. In the study, patients received BMS-986016 80 mg plus Opdivo 240 mg IV once every two weeks.
Primary objectives were safety and objective response rate (ORR; complete [CR] + partial [PR] response), disease control rate (DCR; CR + uCR + PR + uPR + stable disease [SD] > 12 weeks), and duration of response (RECIST v1.1).
As of data cut-off, 212 patients have been treated, including 55 patients with melanoma with prior anti-PD-1/PD-L1 therapy, of which 48 were response evaluable. Treatment-related adverse events of any grade occurred in 45 percent of patients, with 9 percent of patients experiencing Grade 3/4 adverse events.
The data reported at ASCO pertain to an expansion cohort in melanoma.
About LAG-3
Lymphocyte-activation gene 3 (LAG-3) is an immune checkpoint receptor protein found on the cell surface of effector T cells and regulatory T cells (Tregs) and functions to control T cell response, activation and growth. Preclinical studies suggest that inhibiting LAG-3 allows T cells to regain their cytotoxic function and potentially affect tumor growth. LAG-3 expression is also being evaluated as a biomarker to predict response to treatment. Early research suggests that targeting the LAG-3 pathway in combination with other potentially complementary immune pathways may be a key strategy to more effectively activate the antitumor immune response.
Bristol-Myers Squibb is evaluating its anti-LAG-3 BMS-986016 in clinical trials in combination with other agents in a variety of tumor types.
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.
INDICATIONS
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 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: 68
Phase 1/2a data demonstrate encouraging activity of anti-LAG-3 (BMS-986016) and Opdivo combination in heavily pretreated advanced melanoma patients who were relapsed or refractory on anti-PD-1/PD-L1 therapy
Analyses suggest LAG-3 biomarker may be promising to identify patients who are more likely to benefit from this therapeutic combination
Combination of two checkpoint inhibitors had a similar safety profile to Opdivo monotherapy
PRINCETON, NJ, USA I June 3, 2017 I Bristol-Myers Squibb Company (NYSE:BMY) today announced proof-of-concept data showing preliminary efficacy for BMS-986016, an investigational anti-lymphocyte-activation gene 3 (LAG-3) therapy in combination with Opdivo (nivolumab) in patients with advanced melanoma previously treated with anti-PD-1/PD-L1 therapy (n=55). In the ongoing expansion study of heavily pretreated patients who were refractory to or relapsed on anti-PD1/PDL1 therapy, the objective response rate (ORR) was 12.5 percent in evaluable patients (n=48). Patients with LAG-3 expression in at least 1 percent (n=25) of tumor-associated immune cells within the tumor margin had a nearly three-fold improvement in ORR compared to patients with less than 1 percent LAG-3 expression (n=14) (20 percent and 7.1 percent, respectively). These data will be presented today, Saturday, June 3, at the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO) in a poster from 1:15 p.m. – 4:45 p.m. CDT and poster discussion from 4:45 p.m. – 6 p.m. CDT (Abstract #9520).
For some tumor types, immunotherapy is becoming a standard of care, but there are growing numbers of patients who are refractory to or relapse on anti-PD-1/PD-L1 therapy and these patients typically have poor outcomes. These proof-of-concept data show that combining anti-LAG-3 with Opdivo in PD-1/PD-L1 refractory patients may help patients overcome resistance and restore T cell function.
“As a potentially synergistic immune pathway to PD-1/PD-L1, LAG-3 has emerged as an immune checkpoint receptor that regulates T cell function and whose inhibition may increase benefits for patients,” said Paolo Ascierto, M.D., Istituto Nazionale Tumori Fondazione Pascale of Naples, Italy. “These results indicate that BMS-986016 in combination with Opdivo may offer clinical benefit, particularly for patients whose tumors contain immune cells that express LAG-3. Further investigation is warranted to understand the impact of this combination as well as the utility of LAG-3 as an immune biomarker.”
“Advances in immunotherapy have been transformational for many cancer patients, but unfortunately some patients do not respond well or even relapse after an initial response to treatment,” said Fouad Namouni, M.D. head of Oncology Development, Bristol-Myers Squibb. “Across our portfolio, we are actively working to characterize the underlying biology for anti-PD-1/PD-L1 resistant tumors and to determine predictive biomarkers to inform rational treatment combinations. We are very encouraged by these results demonstrating a potential role for anti-LAG3 in this setting and look forward to the ongoing broader investigation of LAG-3 as an alternative therapeutic target and predictive biomarker.”
Bristol-Myers Squibb is developing an oncology pipeline of more than 21 clinical agents with a range of mechanisms and translational approaches, applying evidence-based scientific understanding of the complex and multifactorial immune system.
About the Study
CA224-020 is a Phase 1/2a open label, dose escalation and cohort expansion study of the safety, tolerability and efficacy of an anti-LAG-3 monoclonal antibody in combination with Opdivo in advanced solid tumors. In the study, patients received BMS-986016 80 mg plus Opdivo 240 mg IV once every two weeks.
Primary objectives were safety and objective response rate (ORR; complete [CR] + partial [PR] response), disease control rate (DCR; CR + uCR + PR + uPR + stable disease [SD] > 12 weeks), and duration of response (RECIST v1.1).
As of data cut-off, 212 patients have been treated, including 55 patients with melanoma with prior anti-PD-1/PD-L1 therapy, of which 48 were response evaluable. Treatment-related adverse events of any grade occurred in 45 percent of patients, with 9 percent of patients experiencing Grade 3/4 adverse events.
The data reported at ASCO pertain to an expansion cohort in melanoma.
About LAG-3
Lymphocyte-activation gene 3 (LAG-3) is an immune checkpoint receptor protein found on the cell surface of effector T cells and regulatory T cells (Tregs) and functions to control T cell response, activation and growth. Preclinical studies suggest that inhibiting LAG-3 allows T cells to regain their cytotoxic function and potentially affect tumor growth. LAG-3 expression is also being evaluated as a biomarker to predict response to treatment. Early research suggests that targeting the LAG-3 pathway in combination with other potentially complementary immune pathways may be a key strategy to more effectively activate the antitumor immune response.
Bristol-Myers Squibb is evaluating its anti-LAG-3 BMS-986016 in clinical trials in combination with other agents in a variety of tumor types.
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.
INDICATIONS
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 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: 68
