An additional 1-year follow-up confirmed initial findings that adding pembrolizumab to standard platinum-pemetrexed chemotherapy improves overall survival (OS) by 21% compared to chemotherapy alone.
An expanded analysis of all patients enrolled in IND227 also found that pembrolizumab alone improved OS by 13% compared with chemotherapy alone, and chemotherapy plus pembrolizumab improved OS by 24% compared with chemotherapy alone. The initial results, published in 2023, excluded patients on pembrolizumab monotherapy.
“The survival improvement with the addition of pembrolizumab to standard platinum-pemetrexed chemotherapy in advanced pleural mesothelioma is maintained with additional follow-up,” said Scott Laurie, MD, Professor of Medicine at the University of Ottawa, Canada. “Interestingly, the median OS with pembrolizumab alone was reasonable and could warrant additional study.”
During the 2025 World Conference on Lung Cancer (WCLC), Dr. Laurie discussed longer-term follow-up and exploratory analyses of IND227 during an oral abstract session titled Novel Clinical Approaches and Translational Investigation in Mesothelioma. He noted that initial data from the international, multi-site trial supported approval of pembrolizumab plus chemotherapy for mesothelioma in the US, European Union (EU), Canada, and Japan, among other countries.
The initial analysis excluded patients who had been randomly assigned to receive pembrolizumab alone and other individuals. Dr. Laurie presented both the updated OS for the initial cohort of 440 patients randomly assigned to either pembrolizumab plus chemotherapy or chemotherapy alone, as well as an exploratory, unplanned OS analysis of all 520 enrolled patients.
He also presented a planned immunohistochemistry analysis of BAP1 and MTAP correlated with survival using banked tissue samples.
OS for the original 440-patient cohort was extended 1 year for a median follow-up of 16.2 months. The median OS was 16.13 months for chemotherapy alone with longer follow-up, compared with 17.28 months for chemotherapy plus pembrolizumab. The hazard ratio (HR) for OS remained unchanged at 0.79 (95% CI 0.64–0.97). The log-rank p value decreased from 0.324 to 0.022.
A planned OS histologic analysis showed a median OS of 18.4 months and 19.91 months, respectively, for chemotherapy compared with chemotherapy plus pembrolizumab for epithelioid mesothelioma (HR 0.87, 95% CI 0.66–1.10) and 8.21 months versus 12.16 months, respectively, for non-epithelioid disease (HR 0.59, 95% CI 0.38–0.90).
An exploratory analysis of BAP1 and MTAP immunostains found that BAP1 loss was associated with better survival; however, BAP1 loss was not predictive of treatment effect.
Similarly, MTAP loss was associated with worse OS, with 15.7 months in the MTAP-loss group compared with 19.2 months in the MTAP-retained group (p = 0.035). MTAP loss was not predictive of treatment effect, and there was no significant co-occurrence of MTAP loss and BAP1 loss.
The new analysis, based on all 520 initially enrolled patients, showed a median OS of 15.24 months for the chemotherapy-only arm. Adding pembrolizumab to chemotherapy increased OS to 17.5 months (HR 0.76, 95% CI 0.62–0.92), while pembrolizumab monotherapy had an OS of 16.82 months (HR 0.87, 95% CI 0.62–1.24).
