Bristol Myers Squibb announced results for the co-primary endpoint for CheckMate -915, a randomized Phase 3 study evaluating Opdivo (nivolumab) plus Yervoy (ipilimumab) versus Opdivo for patients who have had a complete surgical removal of stage IIIb/c/d or stage IV melanoma. The addition of Yervoy to Opdivo in this trial did not result in a statistically significant improvement in recurrence-free survival (RFS) in the all-comer (intent-to-treat) population. CheckMate -915 reinforced the established benefit of Opdivo monotherapy as a standard of care in the adjuvant setting. The safety profiles for Opdivo monotherapy and the combination of Opdivo plus Yervoy were consistent with previously reported studies at this dose and schedule (Opdivo 240 mg intravenously every two weeks plus Yervoy 1 mg/kg every six weeks or Opdivo 480 mg every four weeks for up to one year), with no new safety signals observed.
“We are proud of our legacy in melanoma with both Opdivo and Yervoy. They have each brought significant benefit as monotherapies for appropriate melanoma patients in the adjuvant setting, and as a dual immunotherapy regimen in the metastatic setting. In CheckMate -915, we evaluated adding Yervoy to Opdivo against Opdivo – an established, active comparator and current standard of care in the adjuvant setting. We designed this study to determine if dual immunotherapy has the potential to bring additional benefits to patients in this setting, understanding the high benchmark we would need to exceed with this trial,” said Sabine Maier, M.D., vice president, Head of Oncology Clinical Development, Bristol Myers Squibb. “We remain committed to continued research in melanoma, both to further understand the potential benefit of Yervoy in combination with Opdivo to treat high-risk melanoma patients in the earlier stages of disease, as well as to study additional novel combinations in various settings.”
Bristol Myers Squibb will complete a full evaluation of the CheckMate -915 data and work with investigators to share the results at an upcoming medical conference.
Bristol Myers Squibb thanks the patients and investigators who were involved in the CheckMate -915 clinical trial.
About CheckMate -915
CheckMate -915 is a Phase 3, randomized, placebo-controlled, double-blind study evaluating Opdivo in combination with Yervoy versus Opdivo monotherapy, an approved standard of care, in patients who have had a complete surgical removal of stage IIIb/c/d or stage IV (per AJCC 8th edition; no evidence of disease) melanoma. Patients enrolled in the trial had no prior systemic anti-cancer treatment for melanoma, except surgery for the melanoma lesion(s) and/or adjuvant radiation therapy after neurosurgical resection for central nervous system lesions. The trial randomized 1,943 patients to receive either Opdivo 240 mg intravenously every two weeks and Yervoy 1 mg/kg every six weeks or Opdivo 480 mg every four weeks for up to one year. In November 2019, Bristol Myers Squibb announced that a statistically significant benefit was not reached for the co-primary endpoint of recurrence-free survival (RFS) in patients whose tumors expressed PD-L1 <1%.
About Melanoma
Melanoma is a form of skin cancer characterized by the uncontrolled growth of pigment-producing cells (melanocytes) located in the skin. Metastatic melanoma is the deadliest form of the disease and occurs when cancer spreads beyond the surface of the skin to other organs. The incidence of melanoma has been increasing steadily for the last 30 years. In the United States, 100,350 new diagnoses of melanoma and more than 6,850 related deaths are estimated for 2020. Globally, the World Health Organization estimates that by 2040, melanoma incidence will reach 466,914, with 105,904 related deaths. Melanoma is mostly curable when treated in its very early stages, however, survival rates decrease if regional lymph nodes are involved. Patients diagnosed with distant metastasis have a five-year survival rate of approximately 27%.
Adjuvant Therapy in Melanoma
Melanoma is separated into five staging categories (Stages 0-IV) based on the in-situ feature, thickness and ulceration of the tumor, whether the cancer has spread to the lymph nodes, and how far the cancer has spread beyond lymph nodes.
Stage III melanoma has generally reached the regional lymph nodes but has not yet spread to distant lymph nodes or to other parts of the body (metastasized) and requires surgical resection of the primary tumor as well as the involved lymph nodes. Some patients may also be treated with adjuvant therapy. Despite surgical intervention, most patients experience disease recurrence and progress to metastatic disease.
Stage IV melanoma occurs when the melanoma has spread beyond the original site and regional lymph nodes to more distant areas of the body. The most common sites of metastasis are to vital organs, soft tissues and distant lymph nodes.
Bristol Myers Squibb: Advancing Oncology Research
At Bristol Myers Squibb, patients are at the center of everything we do. The goal of our cancer research is to increase patients’ quality of life, long-term survival and make cure a possibility. We harness our deep scientific experience, cutting-edge technologies and discovery platforms to discover, develop and deliver novel treatments for patients.
Building upon our transformative work and legacy in hematology and Immuno-Oncology that has changed survival expectations for many cancers, our researchers are advancing a deep and diverse pipeline across multiple modalities. In the field of immune cell therapy, this includes registrational CAR T cell agents for numerous diseases, and a growing early-stage pipeline that expands cell and gene therapy targets, and technologies. We are developing cancer treatments directed at key biological pathways using our protein homeostasis platform, a research capability that has been the basis of our approved therapies for multiple myeloma and several promising compounds in early- to mid-stage development. Our scientists are targeting different immune system pathways to address interactions between tumors, the microenvironment and the immune system to further expand upon the progress we have made and help more patients respond to treatment. Combining these approaches is key to delivering new options for the treatment of cancer and addressing the growing issue of resistance to immunotherapy. We source innovation internally, and in collaboration with academia, government, advocacy groups and biotechnology companies, to help make the promise of transformational medicines a reality for patients.
