CheckMate743 Study Provides Long-Term Data on IO in Mesothelioma

Solange Peters, MD, PhD, the president of the European Society of Medical Oncology (ESMO), discusses the design of the CheckMate743 study (NCT02899299) of doublet immunotherapy (IO) for patients with malignant pleural mesothelioma (MPM).

The phase 3 CheckMate743 study randomized 600 patients with untreated, unresectable MPM. Patients were stratified by epithelioid versus non-epithelioid histology and by gender.

Patients in the IO arm received 3 mg/kg of nivolumab (Opdivo) every 2 weeks and 1 mg/kg ipilimumab (Yervoy) every 6 weeks, while the control arm received chemotherapy consisting of pemetrexed plus cisplatin or carboplatin every 3 weeks for 6 total cycles.

The primary end point was overall survival (OS), and progression-free survival (PFS) was a secondary end point. Patients who received nivolumab/ipilimumab had a median OS of 18.1 months compared with 14.1 months with chemotherapy. As of the 3-year follow-up, the OS rate was 23.2% for the IO arm versus 15.4% for chemotherapy, while their rate of PFS was 13.6% compared with 0.8%. According to Peters, this is the longest-term data on IO in mesothelioma.

The study also gathered data on biomarkers including the 4-gene inflammatory signature score, tumor mutational burden, and lung immune prognostic index. Exploratory analyses suggested that the inflammatory gene signature was associated with better OS in the IO arm.

TRANSCRIPTION:

0:08 | CheckMate743 is a very straightforward study. It is a trial enrolling patients with unresectable pleural mesothelioma, naive from any treatment, with a good performance status. These patients [were] stratified by histology in mesothelioma—we speak about epithelioid versus non-epithelioid—and gender.

Knowing that, 600-plus patients were randomized 1:1 to nivolumab and low-dose ipilimumab for up to 2 years versus the usual platinum-based chemotherapy with cisplatin or carboplatin and pemetrexed for up to 6 cycles. The primary end point is OS. And at this meeting, we're able to update this OS with a minimum follow up of 3 years. So [this is] the longest ever presented data on IO in mesothelioma, as well as for the first time we're able to show some biomarker assessments. So [we’re] trying to identify new biomarkers and best better understand…the biology of mesothelioma.