The agency approved the first and only immunotherapy treatment as a first-line therapy for adult patients with unresectable malignant pleural mesothelioma.
The FDA approved nivolumab (Opdivo) in combination with ipilimumab (Yervoy) for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM), according to Bristol Myers Squibb.
Of note, this is the first and only immunotherapy treatment approved for this patient population. Moreover, the approval comes 6 weeks after the submission of a new supplemental biologics license application that was reviewed under the FDA’s Real-Time Oncology Review (RTOR) pilot program. The review was also conducted under the FDA’s Project Orbis initiative, enabling concurrent review by the health authorities in Australia, Brazil, Canada, and Switzerland.
The FDA based its decision on results from a pre-specified interim analysis from the open-label, multi-center, randomized phase 3 CheckMate -743 trial, designed to evaluate nivolumab plus ipilimumab compared with chemotherapy (pemetrexed and cisplatin or carboplatin) in patients with histologically confirmed unresectable MPM and no prior systemic therapy or palliative radiotherapy within 14 days of initiation of therapy (n = 605).
In total, 303 patients were randomized to receive 3 mg/kg nivolumab every 2 weeks and 1 mg/kg ipilimumab every 6 weeks, and 302 patients were randomized to receive 75 mg/m2 cisplatin or 500 mg/m2 carboplatin AUC 5 plus pemetrexed in 3-week cycles for 6 cycles until disease progression or unacceptable toxicity or, in the combination arm, up to 24 months.
Overall survival (OS) in all randomized patients served as the primary end point. Secondary end points included progression-free survival (PFS), objective response rate (ORR) and duration of response (DOR).
After a minimum of 22.1 months of follow-up, the immunotherapy combination demonstrated superior OS, compared with the standard of care arm (HR, 0.74; 95% CI, 0.61-0.89; P = .002), with a median OS of 18.1 months (95% CI, 16.8-21.5) versus 14.1 months (95% CI, 12.5-16.2), respectively. Two-year OS was 41% with nivolumab plus ipilimumab, compared with 27% with chemotherapy.
In the immunotherapy arm, 23% of patients discontinued treatment due to adverse events (AEs) and 52% had at least 1 dose withheld for an AE. The most frequent grade ¾ AEs included pneumonia, pyrexia, diarrhea, pneumonitis, pleural effusion, dyspnea, acute kidney injury, infusion-related reaction, musculoskeletal pain, and pulmonary embolism.
“Malignant pleural mesothelioma is a rare cancer with limited treatment options. When it is diagnosed in advanced stages, the 5-year survival rate is approximately 10%,” 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, said 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 healthcare providers who care for them.”
Bristol Myers Squibb. 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. Published 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.