Nivolumab Plus Ipilimumab Improves Survival in Frontline Mesothelioma

Sabine Maier, MD

Sabine Maier, MD

Nivolumab (Opdivo) combined with ipilimumab (Yervoy) significantly improved overall survival (OS) versus chemotherapy in previously untreated patients with malignant pleural mesothelioma (MPM), meeting the primary endpoint of the phase III CheckMate-743 trial.¹

The specific chemotherapy administered in the control arm was pemetrexed (Alimta) combined with either cisplatin or carboplatin. The positive OS findings were determined by an independent panel at a prespecified interim analysis. There were no new safety signals with the combination immunotherapy regimen.

“Malignant pleural mesothelioma is a devastating disease that has seen limited treatment advances over the past decade. 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,” Sabine Maier, MD, development lead, thoracic cancers, Bristol Myers Squibb, the manufacturer of nivolumab and ipilimumab, said in a press release.

“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. We look forward to working with investigators to present the results at a future medical meeting, and to discussing them with health authorities,” added Maier.

The open-label, multicenter phase III CheckMate-743 trial randomized patients with previously untreated MPM to nivolumab plus ipilimumab or pemetrexed plus cisplatin or carboplatin. The nivolumab dosage was 3 mg/kg every 2 weeks, and the ipilimumab dosage was 1 mg/kg every 6 weeks. Beyond the primary OS endpoint, secondary endpoints included objective response rate (ORR), disease control rate, progression-free survival, and efficacy measures according to PD-L1 expression level.

Previously reported outcomes from the prospective, single-arm phase II INITIATE trial showed an ORR at 12 weeks of 29% with nivolumab plus ipilimumab in patients with recurrent MPM.² The ORR comprised 10 partial responses among 34 evaluable patients. An additional 13 (38%) evaluable patients achieved stable disease, resulted in a disease control rate of 68% (95% CI, 50-83).

The study enrolled patients between Oct 5, 2016, and Aug 3, 2017. The patients had MPM with progression after ≥1 line of platinum-containing chemotherapy. Patients had an ECOG performance status of 0 or 1.

Nivolumab was administered at 240 mg every 2 weeks and ipilimumab was administered at 1 mg/kg every 6 weeks up to 4 times. Patients received therapy until disease progression, unacceptable toxicity, or a maximum of 2 years.

The safety population included 35 patients. Overall, 94% of these patients experienced at least 1 treatment-related adverse event (TRAE). Infusion-related reactions, skin disorders, and fatigue were the most common AEs. Thirty-four percent (n = 12) of 35 patients experienced grade 3 TRAEs.

References

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 Online April 20, 2020. https://bit.ly/3eBgIBc. Accessed April 20, 2020.
2. Disselhorst MJ, Quispel-Janssen J, Lalezari F, et al. Ipilimumab and nivolumab in the treatment of recurrent malignant pleural mesothelioma (INITIATE): results of a prospective, single-arm, phase 2 trial. Clinical Trial Lancet Respir Med. 2019;7(3):260-270. doi: 10.1016/S2213-2600(18)30420-X