FDA Approves Nivolumab Plus Ipilimumab for Previously Untreated Unresectable Malignant Pleural Mesothelioma

The FDA today granted approval to intravenous nivolumab (Opdivo, Bristol-Meyers Squibb), 360 mg every 3 weeks, plus ipilimumab (Yervoy), 1 mg/kg every 6 weeks, for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM).

This is the third approved indication for a nivolumab plus ipilimumab-based combination in the first-line treatment of a form of thoracic cancer. The combination has also been approved by the FDA as a first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express programmed death-ligand 1 (PD-L1) ≥ 1% as determined by an FDA-approved test, and without EGFR or ALK genomic tumor aberrations.

Nivolumab plus ipilimumab has also been approved in combination with limited chemotherapy for the first-line treatment of adult patients with metastatic or recurrent NSCLC with no EGFR or ALK genomic tumor aberrations regardless of PD-L1 expression.

“(MPM) is a rare cancer with limited treatment options. When it is diagnosed in advanced stages, the 5-year survival rate is approximately 10%,” said study investigator Anne S. Tsao, MD, professor and section chief, Thoracic Medical Oncology, and director of the Mesothelioma Program at The University of Texas MD Anderson Cancer Center, in a press release. “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. This is exciting news, instilling hope for patients with this devastating disease and for the health care providers who care for them.”

This approval was based on a pre-specified interim analysis from the phase 3 CheckMate -743 trial. The study showed that the nivolumab plus ipilimumab combination (n=303) demonstrated superior overall survival (OS) compared with the platinum-based standard of care chemotherapy (n=302) (HR: 0.74 [95% CI: 0.61 to 0.89]; P=0.002).

The nivolumab plus ipilimumab combination showed a median OS of 18.1 months (95% CI: 16.8 to 21.5) compared with 14.1 months (95% CI: 12.5 to 16.2) with chemotherapy after 22.1 months of minimum follow-up. At 2 years, the researchers found that 41% of patients administered nivolumab plus ipilimumab were alive compared with 27% of patients on chemotherapy.

The combination was associated with immune-mediated warnings and precautions that include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, skin adverse reactions, and encephalitis. Ipilimumab is associated with severe and fatal immune-mediated adverse events, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplant after ipilimumab, embryo-fetal toxicity, and risks associated when administered in combination with nivolumab.

“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,” said Adam Lenkowsky, general manager and head, US, Oncology, Immunology, Cardiovascular, Bristol Myers Squibb, in a press release. “Just a few months ago, Opdivo plus Yervoy-based combinations received two first-line indications for certain patients with non-small cell lung cancer. Now, Opdivo plus Yervoy is approved for use in another type of thoracic cancer, previously untreated unresectable MPM. With today’s announcement, Opdivo plus 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.”

Reference

U.S. Food and Drug Administration Approves Opdivo® (nivolumab) + Yervoy® (ipilimumab) as the First and Only Immunotherapy Treatment for Previously Untreated Unresectable Malignant Pleural Mesothelioma. Bristol Myers Squibb. October 2, 2020. https://news.bms.com/news/details/2020/U.S.-Food-and-Drug-Administration-Approves-Opdivo-nivolumab--Yervoy-ipilimumab-as-the-First-and-Only-Immunotherapy-Treatment-for-Previously-Untreated-Unresectable-Malignant-Pleural-Mesothelioma/default.aspx. Accessed October 2, 2020.