Bristol Myers Squibb’s CheckMate -743 phase 3 trial of Opdivo in combo with Yervoy to treat malignant pleural mMesothelioma meets primary endpoint
Bristol-Myers Squibb announced that CheckMate -743, a pivotal phase 3 trial evaluating Opdivo (nivolumab) in combination with Yervoy (ipilimumab) in previously untreated malignant pleural mesothelioma (MPM) met its primary endpoint of overall survival (OS). Based on a pre-specified interim analysis conducted by the independent Data Monitoring Committee, Opdivo in combination with Yervoy resulted in a statistically significant and clinically meaningful improvement in OS compared to chemotherapy (pemetrexed and cisplatin or carboplatin).
The safety profile of Opdivo plus Yervoy observed in the trial reflects the known safety profile of the combination.
“Malignant pleural mesothelioma is a devastating disease that has seen limited treatment advances over the past decade,” said Sabine Maier, M.D., development lead, thoracic cancers, Bristol Myers Squibb. “These topline results from the CheckMate -743 trial demonstrate the potential of Opdivo plus Yervoy in previously untreated patients with malignant pleural mesothelioma, and is another example of the established efficacy and safety of the dual immunotherapy combination seen in multiple tumor types. We would like to thank the patients who participated in this trial, as well as the investigators and site personnel for their perseverance during the conduct of this study and in delivering this important result for patients in the midst of the COVID-19 pandemic. We look forward to working with investigators to present the results at a future medical meeting, and to discussing them with health authorities.”
CheckMate -743 is an open-label, multi-center, randomized phase 3 trial evaluating Opdivo plus Yervoy compared to chemotherapy (pemetrexed and cisplatin or carboplatin) in patients with previously untreated malignant pleural mesothelioma (MPM). Opdivo is administered at 3 mg/kg every two weeks and Yervoy at 1 mg/kg every six weeks. The primary endpoint of the trial was OS. Secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and efficacy measures according to PD-L1 expression level.
Malignant pleural mesothelioma is a rare but aggressive form of cancer that forms in the lining of the lungs. It is most frequently caused by exposure to asbestos. Diagnosis is often delayed, with the majority of patients having advanced or metastatic disease at presentation. Prognosis is generally poor: in previously untreated patients with advanced or metastatic malignant pleural mesothelioma, median survival is less than one year and the five-year survival rate is approximately 10%.
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 treated more than 35,000 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 65 countries, including the United States, the European Union, Japan and China. 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.
Yervoy is a recombinant, human monoclonal antibody that binds to the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). CTLA-4 is a negative regulator of T-cell activity. Yervoy binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation, including the activation and proliferation of tumor infiltrating T-effector cells.
Inhibition of CTLA-4 signaling can also reduce T-regulatory cell function, which may contribute to a general increase in T-cell responsiveness, including the anti-tumor immune response. On March 25, 2011, the US Food and Drug Administration (US FDA) approved Yervoy 3 mg/kg monotherapy for patients with unresectable or metastatic melanoma. Yervoy is approved for unresectable or metastatic melanoma in more than 50 countries. There is a broad, ongoing development program in place for Yervoy spanning multiple tumor types.
