FDA Approves Opdivo-Yervoy Combo as First-Line Therapy for Inoperable Mesothelioma

FDA Approves Opdivo-Yervoy Combo as First-Line Therapy for Inoperable Mesothelioma

The U.S. Food and Drug Administration (FDA) has approved a combination of Opdivo (nivolumab) and Yervoy (ipilimumab) as a first-line therapy for adults with inoperable malignant pleural mesothelioma (MPM), a rare but aggressive cancer that affects the lungs’ protective tissue lining.

The FDA’s decision was announced less than six weeks after Bristol Myers Squibb, the therapies’ developer, submitted an application requesting the approval of the combo therapy for this indication. The speedy approval was made possible by the FDA’s Real-Time Oncology Review pilot program and the Project Orbis initiative, which aim to make safe and effective cancer treatments available to patients as early as possible.

The European Medicines Agency (EMA) also has agreed to review a similar request for approval of the combination therapy in Europe.

This is the third time Opdivo plus Yervoy has been approved as a first-line therapy to treat a form of thoracic (lung) cancer — the other two were for non-small cell lung cancer (NSCLC) — and the seventh time overall, with previous approvals for melanomacolonkidney, and liver cancers.

“Thoracic cancers can be complex and difficult to treat, and we are focused on developing immunotherapy options that may have the potential to extend patients’ lives,” Adam Lenkowsky, general manager and U.S. head of oncology, immunology, and cardiovascular at Bristol Myers Squibb, said in a press release.

“With today’s announcement, Opdivo + Yervoy becomes the first new systemic therapy approved in more than 15 years in this setting, and may offer these patients a chance for a longer life,” Lenkowsky said.

Opdivo and Yervoy belong to a class of medications called immune checkpoint inhibitors. By suppressing certain “checkpoint” proteins found on the surface of immune T-cells, these medicines enhance T-cells’ ability to recognize and destroy cancer cells.

While Yervoy acts on the CTLA-4 protein, Opdivo blocks another protein called PD-1. Blocking either checkpoint protein can limit cancer growth, but targeting both is thought to amplify the overall effect. This is because Yervoy can activate new T-cells, some of which become long-lasting memory-T-cells, while Opdivo can help existing T-cells locate tumors.

The FDA’s decision to approve the combination of Opdivo and Yervoy for this indication was based on an interim analysis of an ongoing Phase 3 trial, called CheckMate-743 (NCT02899299).

CheckMate-743 is currently comparing the safety and effectiveness of the Opdivo-Yervoy combo therapy with standard chemotherapy regimens (cisplatin or carboplatin plus pemetrexed) in 605 untreated patients with inoperable MPM.

Participants receiving the combination therapy will continue treatment for up to two years, unless their disease progresses before then or they show signs of unacceptable toxicity. Those assigned to chemo will receive treatment for up to six cycles, or until disease progression or unacceptable toxicity.

Data from the study’s pre-specified interim analysis showed the Opdivo-Yervoy combo therapy prolonged the time patients lived from a median of 14.1 to 18.1 months, lowering the risk of death by 26%.

At two years of follow-up, 41% of the patients treated with the combo therapy were still alive, while only 27% of those receiving a platinum-based chemotherapy regimen still lived.

Notably, these survival benefits were also observed in a sub-group of patients with a non-epithelioid form of MPM, which is usually associated with a poorer prognosis.

“Malignant pleural mesothelioma is a rare cancer with limited treatment options. When it is diagnosed in advanced stages, the five-year survival rate is approximately 10 percent,” said Anne S. Tsao, MD, professor and director of the mesothelioma program at the University of Texas M.D. Anderson Cancer Center, and one of the study’s investigators.

“The survival results from the CheckMate-743 trial show that the combination of nivolumab and ipilimumab could become a new front-line standard of care option.” Tsao said. “This is exciting news, instilling hope for patients with this devastating disease and for the healthcare providers who care for them.”

The safety profile of the Opdivo-Yervoy combo in CheckMate-743 was consistent with previous studies. No new safety signals were identified.

The most common side effects observed in the study included fatigue (43%), muscle pain (38%), rash (34%), diarrhea (32%), shortness of breath (27%), nausea (24%), decreased appetite (24%), cough (23%), and itching (21%).

Both Opdivo and Yervoy can cause immune-mediated complications that are listed on the “Warnings and Precautions” section of the medications’ prescribing information, which can be found here and here.

The FDA advises patients to alert their doctors if they have problems of the immune system, lungs, or liver, have had an organ transplant, and are pregnant or plan to become pregnant, before taking Yervoy.