BMS Submits Application for Opdivo Plus Yervoy as First-Line Treatment for Malignant Pleural Mesothelioma Based on CheckMate-743 Trial

September 16, 2020 /BioValleyBIOON/ -- Bristol-Myers Squibb (BMS) recently announced that the European Medicines Agency (EMA) has accepted the Type II variation application for the first-line treatment of malignant pleural mesothelioma (MPM) with the anti-PD-1 therapy Opdivo (nivolumab) in combination with the anti-CTLA-4 therapy Yervoy (ipilimumab), and has initiated the centralized review procedure.

This Class II change application is supported by the pivotal Phase III CheckMate-743 study. Notably, CheckMate-743 is the first and only Phase III trial demonstrating that first-line immunotherapy significantly improves survival in patients with malignant pleural mesothelioma (MPM). The results showed that, among all randomized patients, Opdivo plus Yervoy dual immunotherapy (the OY combination) demonstrated a durable survival benefit, meeting the primary endpoint of prolonged overall survival (OS) compared with chemotherapy (pemetrexed plus cisplatin or carboplatin). Its safety profile was consistent with previous studies of Opdivo and Yervoy.

Opdivo + Yervoy is a unique combination of two immune checkpoint inhibitors with potential synergistic mechanisms, targeting two distinct checkpoints (PD-1 and CTLA-4) to help destroyTumorcells. To date, the Opdivo + Yervoy combination therapy has been approved for six treatment indications across five types of cancer (Melanoma, renal cell carcinoma, colorectal cancer, hepatocellular carcinoma, non-small cell lung cancer).

Bristol-Myers SquibbTumorSabine Maier, Vice President of Clinical Development, stated: “Malignant pleural mesothelioma is not only a particularly aggressive cancer, but it has also proven difficult to treat, with no new options approved for many years that can meaningfully prolong survival. The CheckMate-743 trial demonstrated the potential of Opdivo plus Yervoy to address this significant unmet need. We look forward to collaborating with the EMA to achieve our goal of making this dual immunotherapy available to patients in Europe.”

CheckMate-743 is an open-label, multicenter, randomized phase IIIClinical TrialA total of 605 patients with previously untreated, unresectable malignant pleural mesothelioma (MPM) were enrolled to evaluate the efficacy and safety of Opdivo plus Yervoy dual immunotherapy as first-line treatment, compared with chemotherapy (pemetrexed plus cisplatin or carboplatin). Patients were randomized to receive either Opdivo plus Yervoy (n=303) or chemotherapy (n=302). In the Opdivo plus Yervoy arm, Opdivo was administered at a dose of 3 mg/kg every two weeks, and Yervoy at 1 mg/kg every six weeks, for up to 24 months or until disease progression or unacceptable toxicity. In the chemotherapy arm, patients received cisplatin 75 mg/m² or carboplatin AUC 5 in combination with pemetrexed 500 mg/m² on a 21-day cycle for up to six cycles, or until disease progression or unacceptable toxicity. The primary endpoint of the study was overall survival (OS) in all randomized patients.

The results showed that the study met its primary endpoint: compared with the chemotherapy group, the Opdivo + Yervoy group demonstrated a significant improvement in overall survival (median LS: 18.1 months vs. 14.1 months), with a 26% reduction in the risk of death (HR=0.74; 96.6% CI: 0.60–0.91; p=0.002). At 2 years, the survival rate was 41% in the Opdivo + Yervoy group versus 27% in the chemotherapy group.

Histology is a recognized prognostic factor in mesothelioma, with patients having non-epithelioid histology generally experiencing poorer outcomes. In the CheckMate-743 study, Opdivo plus Yervoy demonstrated improved overall survival (OS) in both non-epithelioid and epithelioid malignant pleural mesothelioma (MPM), with a greater survival benefit observed in the non-epithelioid subgroup. Specifically, the median OS was 18.7 months for epithelioid patients and 18.1 months for non-epithelioid patients treated with Opdivo plus Yervoy, compared to 16.5 months for epithelioid patients and 8.8 months for non-epithelioid patients treated with chemotherapy (epithelioid subgroup: HR=0.86 [95% CI: 0.69, 1.08]; non-epithelioid subgroup: HR=0.46 [95% CI: 0.31, 0.68]).

In this study, the safety profile of the dual immunotherapy with Opdivo plus Yervoy was consistent with previously reported studies, and no new safety signals were observed.

Malignant Pleural Mesothelioma (MPM) is a rare and highly aggressiveTumor, which forms in the lining of the lungs. The most common cause of this disease is exposure to asbestos. MPM'sDiagnosisOften delayed, most patients present with advanced or metastatic disease at the time of diagnosis, and the prognosis is generally poor: in previously untreated patients with advanced or metastatic MPM, the median survival is <1 year, and the 5-year survival rate is approximately 10%.

MPM is a devastating disease with very limited therapeutic progress over the past 15 years. The positive top-line results from the CheckMate-743 trial demonstrated the potential of the Opdivo + Yervoy combination regimen as first-line treatment for MPM, while also in multipleTumorAnother example demonstrating the efficacy and safety of this dual immunotherapy combination within the type.

Opdivo and Yervoy are both immuno-oncology (I-O) therapies that harness the body’s own immune system to combat tumors by targeting distinct regulatory components of the immune system. Opdivo works by blocking the PD-1/PD-L1 pathway, while Yervoy targets CTLA-4. Currently, Bristol-Myers Squibb is developing the Opdivo plus Yervoy immunotherapy combination for multiple typesTumortreatment.

Opdivo + Yervoy is from the United StatesFDAThe only approved dual immunotherapy, this therapy features a potential synergistic mechanism of action, targeting two distinct immune checkpoints (PD-1 and CTLA-4) and functioning in a complementary manner. In terms of U.S. regulatory approvals, the Opdivo + Yervoy combination therapy has been approved for six treatment indications across five cancer types (Melanoma, renal cell carcinoma, colorectal cancer, hepatocellular carcinoma, non-small cell lung cancer). (Bioon.com)

Original Source: European Medicines Agency Validates Bristol-Myers Squibb’s Type II Variationapplication for Opdivo (nivolumab) Plus Yervoy (ipilimumab) for First-line Treatment of Malignant Pleural Mesothelioma