SILVER SPRING, Md.—Today the U.S. Food and Drug Administration (FDA) announced its approval of Opdivo (nivolumab) in combination with Yervoy (ipilimumab) for the first-line treatment of adults with malignant pleural mesothelioma that cannot be removed by surgery. The approval was granted to Bristol-Myers Squibb.
This is the first drug regimen approved for mesothelioma in 16 years, and only the second FDA-approved systemic therapy for mesothelioma. The approval is based on interim analysis from the Phase 3 CheckMate-743 trial, in which Opdivo + Yervoy demonstrated superior overall survival versus platinum-based standard of care chemotherapy.
“Today’s approval of nivolumab plus ipilimumab provides a new treatment that has demonstrated an improvement in overall survival for patients with malignant pleural mesothelioma,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “In 2004, FDA approved pemetrexed in combination with cisplatin for this indication, and now patients now have an important, additional treatment option after more than a decade with only one FDA-approved drug regimen.”
Malignant pleural mesothelioma (MPM) is a life-threatening cancer of the lungs’ lining, caused by inhaling asbestos fibers. MPM accounts for most mesothelioma diagnoses, and most patients have an unresectable tumor at time of diagnosis. Overall survival is generally poor.
Opdivo and Yervoy are both monoclonal antibodies that, when combined, decrease tumor growth by enhancing T-cell function. Opdivo/Yervoy combination therapy was evaluated during a randomized, open-label trial in 605 patients with previously untreated, unresectable MPM. Patients received intravenous infusions of Opdivo every two weeks, with intravenous infusions of Yervoy every six weeks for up to two years, or platinum-doublet chemotherapy for up to six cycles. Treatment continued until disease progression, unacceptable toxicity or the end of two years.
The objective of the trial was to determine if Opdivo in combination with Yervoy improved overall survival compared to chemotherapy. At the time of the analysis, patients who received Opdivo in combination with Yervoy had a median overall survival of 18.1 months versus 14.1 months, respectively. These results were observed after 22.1 months of minimum follow-up.
At two years, 41 percent of patients treated with Opdivo + Yervoy were alive, and 27 percent of those treated with chemotherapy were alive.
“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,” noted study investigator Anne S. Tsao, M.D., professor, section chief of Thoracic Medical Oncology and director of the mesothelioma program at the University of Texas M.D. Anderson Cancer Center. “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.”
The most common side effects of Opdivo in combination with Yervoy in patients with MPM include fatigue, musculoskeletal pain, rash, diarrhea, dyspnea, nausea, decreased appetite, cough and pruritus. Yervoy can also cause serious conditions known as immune-mediated side effects: including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, skin adverse reactions, encephalitis, infusion reactions, complications of stem-cell transplant using donor stem cells, and embryo-fetal toxicity.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, the FDA collaborated with the Australian Therapeutic Goods Administration, the Brazilian Health Regulatory Agency, Health Canada and Switzerland’s Swissmedic. Application reviews are ongoing at the other regulatory agencies.
The FDA approval was granted less than six weeks following the submission of a new supplemental Biologics License Application (sBLA), which was reviewed under the FDA’s Real-Time Oncology Review (RTOR) pilot program. The RTOR program aims to ensure that safe and effective treatments are available to patients as early as possible.
This is the third indication for an Opdivo + Yervoy-based combination in the first-line treatment of a form of thoracic cancer. Opdivo + Yervoy is approved by the FDA as a first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1≥1% as determined by an FDA-approved test, without EGFR or ALK genomic tumor aberrations. The combination is also 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.
“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. Just a few months ago, Opdivo + Yervoy-based combinations received two first-line indications for certain patients with non-small cell lung cancer. Now, Opdivo + Yervoy is approved for use in another type of thoracic cancer, previously untreated unresectable MPM,” added Adam Lenkowsky, general manager and U.S. head of Oncology, Immunology and Cardiovascular at Bristol Myers Squibb. “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.”