The trial evaluating nivolumab in combination with ipilimumab in previously untreated malignant pleural mesothelioma met its primary endpoint of overall survival.
The CheckMate-743 trial evaluating nivolumab (Opdivo) in combination with ipilimumab (Yervoy) in previously untreated malignant pleural mesothelioma met its primary endpoint of overall survival (OS), according to Bristol-Myers Squibb, the agent’s developer.1
Based on a pre-specified interim analysis conducted by an independent data monitoring committee, the combination treatment was also found to result in a statistically significant and clinically meaningful improvement in OS compared to chemotherapy (pemetrexed and cisplatin or carboplatin). Additionally, the safety profile of nivolumab plus ipilimumab observed in the trial reflects the known safety profile of the combination.
“Malignant pleural mesothelioma is a devastating disease that has seen limited treatment advances over the past decade,” Sabine Maier, MD, development lead of thoracic cancers at Bristol Myers Squibb, said in a press release. “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.”
“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.”
Overall, 606 participants with unresectable pleural mesothelioma were randomized to either nivolumab plus ipilimumab or pemetrexed plus cisplatin or carboplatin. Patients randomized to the nivolumab plus ipilimumab combination were administered 3 mg/kg of nivolumab every 2 weeks and 1 mg/kg of ipilimumab every 6 weeks.2
Secondary endpoints for the trial included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and efficacy measures according to PD-L1 expression level.
In the single-center, single-arm, phase II INITIATE trial researchers assessed nivolumab plus ipilimumab in patients with malignant pleural mesothelioma who progressed after at least 1 line of platinum-containing chemotherapy. The study enrolled patients between October 5, 2016, and August 3, 2017.
Participants were administered 240 mg of nivolumab every 2 weeks and 1 mg/kg of ipilimumab every 6 weeks up to 4 times. Only 34 of the 38 enrolled patients were evaluable for response assessment at 12 weeks, with 10 (29%) achieving a partial response and 13 (38%) demonstrating stable disease. This resulted in an overall disease control rate of 68% (95% CI, 50-83).
Notably, treatment-related adverse events (AEs) were reported in 33 (94%) patients. The most AEs were infusion-related reactions, skin disorders, and fatigue. Further, grade 3 treatment-related AEs were reported in 12 (34%) of 35 patients.
1. 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. Published April 20, 2020. news.bms.com/press-release/corporatefinancial-news/bristol-myers-squibb-announces-positive-topline-result-pivotal. Accessed April 20, 2020.
2. Disselhorst MJ, Quispel-Janssen J, Lalezari F, et a. Ipilimumab and nivolumab in the treatment of recurrent malignant pleural mesothelioma (INITIATE): results of a prospective, single-arm, phase 2 trial. Lancet. doi:10.1016/S2213-2600(18)30420-X.