“These topline results from the CheckMate 743 trial demonstrate the potential of Opdivo plus Yervoy in previously untreated patients with malignant pleural mesothelioma, and is another example of the established efficacy and safety of the dual immunotherapy combination seen in multiple tumor types.”
Nivolumab (Opdivo) in combination with ipilimumab (Yervoy) demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) in patients with previously untreated malignant pleural mesothelioma (MPM); this met the primary end point of the CheckMate 743 trial, according to interim results released by Bristol Myers Squibb.
The pivotal phase III trial showed no new safety signals from the known safety profile of the immunotherapy combination. Further findings from the trial will be presented at an upcoming medical meeting and submitted to regulatory agencies.
“Malignant pleural mesothelioma is a devastating disease that has seen limited treatment advances over the past decade,” said Sabine Maier, MD, development lead, thoracic cancers, Bristol Myers Squibb, in a statement. “These topline results from the CheckMate 743 trial demonstrate the potential of Opdivo plus Yervoy in previously untreated patients with malignant pleural mesothelioma, and is another example of the established efficacy and safety of the dual immunotherapy combination seen in multiple tumor types.”
CheckMate 743 is an open-label, multicenter, randomized phase III trial that investigated the safety and efficacy of nivolumab and ipilimumab in comparison with chemotherapy as first-line therapy in patients with unresectable MPM (NCT02899299).
Eligible patients were at least 18 years old with histologically confirmed MPM that was not eligible for curative surgery. They were also required to have an ECOG performance status of 0 or 1, acceptable blood work, and available tumor sample for testing. Those with primitive peritoneal, pericardial and tunica vaginalis testis mesotheliomas; active untreated central nervous system metastases; and a history of another malignancy in the last 3 years were excluded from the trial.
Approximately 600 patients were enrolled in the trial. Those in the investigational arm received 3 mg/kg of nivolumab every 2 weeks and 1 mg/kg of ipilimumab every 6 weeks. Chemotherapy in the control arm consisted of pemetrexed and cisplatin or carboplatin.
The primary end point was OS and the secondary end points were objective response rate, disease control rate, progression-free survival, and the correlation of PD-L1 expression with outcomes.
The pre-specified interim analysis was conducted by an independent data monitoring committee.
“We would like to thank the patients who participated in this trial, as well as the investigators and site personnel for their perseverance during the conduct of this study and in delivering this important result for patients in the midst of the COVID-19 pandemic,” Maier added. “We look forward to working with investigators to present the results at a future medical meeting, and to discussing them with health authorities.”
The PD-1/CTLA-4 combination regimen is FDA approved for use in several solid tumor indications, including for patients with unresectable or metastatic melanoma;intermediate or poor risk, previously untreated advanced renal cell carcinoma; hepatocellular carcinoma following treatment with sorafenib (Nexavar); and for patients with microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.
Bristol Myers Squibb Announces Positive Topline Result from Pivotal Phase 3 Trial Evaluating Opdivo® (nivolumab) plus Yervoy® (ipilimumab) vs. Chemotherapy in Previously Untreated Malignant Pleural Mesothelioma [press release]. Princeton, NJ: Bristol Myers Squibb; April 20, 2020.