Bristol Myers Squibb announced that the European Commission (EC) has approved Opdivo (nivolumab) plus Yervoy (ipilimumab) for the first-line treatment of adults with unresectable malignant pleural mesothelioma (MPM). The EC’s decision is based on results from the CheckMate -743 trial, the first and only positive phase 3 study of an immunotherapy in first-line MPM. The trial met its primary endpoint, showing superior overall survival (OS) with Opdivo plus Yervoy versus chemotherapy (pemetrexed and cisplatin or carboplatin) in all randomized patients.
“After many years of limited progress in the treatment of malignant mesothelioma, we saw an important clinical benefit for patients with nivolumab plus ipilimumab in the CheckMate -743 trial,” said Paul Baas, M.D., Ph.D., Department of Thoracic Oncology, Netherlands Cancer Institute and the University of Leiden. “With the European Commission approval of this dual immunotherapy combination, patients and doctors will now have a new treatment option that has shown significant improvements in survival to manage this resistant disease.”
The EC decision allows for the use of Opdivo plus Yervoy in first-line unresectable MPM in the 27 member states of the European Union (EU), as well as Iceland, Liechtenstein and Norway. In addition to the EU, the combination has been approved in six countries, including the United States, and additional regulatory applications are under review by global health authorities.
“Mesothelioma can be a devastating diagnosis for patients and their families, and the disease has a significant impact throughout Europe, which has the highest incidence rate of mesothelioma globally,” said Stefania Vallone, board member, Women against Lung Cancer in Europe. “Mesothelioma is often detected decades after exposure to asbestos, and for years these patients have faced this aggressive cancer with few treatment options. We are pleased to see a new therapy approved that may offer patients and their families hope for a longer life. Our wish is that it will soon be available in all European countries.”
“The European Commission’s approval of Opdivo plus Yervoy is a crucial step in addressing the unmet needs of patients with malignant pleural mesothelioma. In the CheckMate -743 trial, this dual immunotherapy combination demonstrated a clinically meaningful improvement in survival over the standard of care, with 41% of patients who received Opdivo plus Yervoy still alive at two years, compared to only 27% with chemotherapy,” said Abderrahim Oukessou, M.D., vice president, thoracic cancers development lead, Bristol Myers Squibb. “We thank the patients and investigators involved in the CheckMate -743 trial, whose contributions were essential to bringing the first immunotherapy option to mesothelioma patients throughout the EU.”
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 (n=605). Patients with interstitial lung disease, active autoimmune disease, medical conditions requiring systemic immunosuppression, or active brain metastasis were excluded from the trial. In the trial, 303 patients were randomized to receive Opdivo at 3 mg/kg every two weeks and Yervoy at 1 mg/kg every six weeks; 302 patients were randomized to receive cisplatin 75 mg/m2 or carboplatin AUC 5 plus pemetrexed 500 mg/m2 in 21-day cycles for six cycles.
Treatment in both arms continued until disease progression or unacceptable toxicity or, in the Opdivo plus Yervoy arm, up to 24 months. The primary endpoint of the trial was overall survival (OS) in all randomized patients. Additional efficacy outcome measures included progression-free survival (PFS), objective response rate (ORR) and duration of response (DOR), as assessed by blinded independent central review (BICR) utilizing modified RECIST criteria. Exploratory endpoints included safety, pharmacokinetics, immunogenicity and patient reported outcomes.
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 presenting with advanced or metastatic disease.
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.
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.
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