Nivolumab Plus Ipilimumab Improves OS in Malignant Pleural Mesothelioma

August 10, 2020

Data from the phase 3 CheckMate-743 trial showed a statistically significant overall survival benefit for patients with previously untreated, unresectable malignant pleural mesothelioma when treated with nivolumab plus ipilimumab.

The combination use of nivolumab (Opdivo) plus ipilimumab (Yervoy) showed significant improvement in overall survival (OS) compared to chemotherapy for patients with previously untreated, unresectable malignant pleural mesothelioma, Bristol Myers Squibb announced.

Specifically, data from the phase 3 CheckMate-743 clinical trial found a 26% reduction in the risk of death when treated with nivolumab plus ipilimumab. Moreover, at 2 years, 41% of patients treated with the combination were alive compared to just 27% of patients who underwent chemotherapy treatment.

“An aggressive cancer with a five-year survival rate of less than 10%, malignant pleural mesothelioma has shown resistance to many clinical treatments,” Paul Baas, MD, PhD, Department of Thoracic Oncology, Netherlands Cancer Institute and the University of Leiden, said in a press release. “Now, for the first time, we have evidence that a dual immunotherapy combination showed a superior, sustained overall survival benefit compared to chemotherapy in the first-line treatment of all types of malignant pleural mesothelioma. The CheckMate-743 data support the potential for nivolumab plus ipilimumab to become a new standard of care.”

The nivolumab and ipilimumab combination demonstrated a median OS of 18.1 months compared to 14.1 months for platinum-based standard of care chemotherapy (HR, 0.74; 96.6% CI, 0.60-0.91]; P= .002).

The CheckMate-743 trial also showed improvements in survival rates in both non-epithelioid and epithelioid malignant pleural mesothelioma, with a larger magnitude of benefit found in the non-epithelioid subgroup. Median OS was 18.7 months for epithelioid patients (HR, 0.86; 95% CI, 0.69-1.08) and 18.1 months for non-epithelioid patients (HR, 0.46; 95% CI, 0.31-0.68) with the dual immunotherapy combination compared to 16.5 months and 8.8 months, respectively.

CheckMate-743 is an open-label, multi-center, randomized phase 3 trial, where 303 patients received nivolumab at 3 mg/kg every 2 weeks and ipilimumab at 1 mg/kg every 6 weeks for up to 24 months or until disease progression. The primary end point of the trial was OS, with secondary end points including objective response rate, disease control rate, and progression-free survival.

The safety profile for the combination was consistent with previously reported studies, with no new safety signals observed. The data was presented at the 2020 World Conference on Lung Cancer Virtual Presidential Symposium on August 8.

“These data in malignant pleural mesothelioma follow on the established long-term efficacy of Opdivo plus Yervoy in patients with non-small cell lung cancer and further demonstrate the combination’s potential to change survival expectations in thoracic cancers,” Sabine Maier, Vice President of the Oncology Clinical Development for Bristol Myers Squibb, said in a press release.

The treatment with nivolumab and ipilimumab combines 2 immune checkpoint inhibitors that target the PD-1 and CTLA-4 checkpoints to help destroy tumor cells. The ipilimumab activates and proliferates the T-cells, while nivolumab helps the existing T-cells discover the tumors.

Malignant pleural mesothelioma is a rare and aggressive form of cancer that forms in the lining of the lungs, most frequently caused by asbestos. A majority of patients with this form of mesothelioma present with advanced or metastatic disease. Median survival for previously untreated patients with advanced or metastatic malignant pleural mesothelioma is less than 1 year with a 5-year survival rate around 10%.

“For more than 15 years, no new systemic treatment options that can extend survival have been approved for patients with malignant pleural mesothelioma,” said Maier. “We look forward to discussions with global health authorities over the coming months about the positive results from CheckMate-743.”

Reference:

Opdivo® (nivolumab) Plus Yervoy® (ipilimumab) Demonstrates Durable Survival Benefit vs. Chemotherapy in Patients with Previously Untreated Malignant Pleural Mesothelioma [news release]. Princeton, New Jersey. Published August 8, 2020. https://news.bms.com/press-release/corporatefinancial-news/opdivo-nivolumab-plus-yervoy-ipilimumab-demonstrates-durable-s. Accessed August 10, 2020.