LUME-Meso: Design and Rationale of the Phase III Part of a Placebo-Controlled Study of Nintedanib and Pemetrexed/Cisplatin Followed by Maintenance Nintedanib in Patients With Unresectable Malignant Pleural Mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare but aggressive disease: median survival is 6 to 9 months if untreated. Standard first-line treatment for patients with unresectable MPM is cisplatin/pemetrexed, with a median overall survival (OS) of approximately 1 year. Improvements in first-line treatment options are needed. With the benefit of combining bevacizumab with standard therapy shown in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS), vascular endothelial growth factor (VEGF) pathway inhibition has gained renewed interest as a treatment approach. Nintedanib is an oral angiokinase inhibitor targeting multiple signaling pathways implicated in the pathogenesis of MPM, including the VEGF receptor. The phase III part of the international, phase II/III LUME-Meso study is evaluating the efficacy and safety of nintedanib plus pemetrexed/cisplatin in patients with unresectable epithelioid MPM. Originally, this was a double-blind, randomized, phase II exploratory study and was amended to include a confirmatory phase III part following the recommendation of an internal Data Monitoring Committee and review of phase II data. The phase III part plans to enroll 450 chemotherapy-naive patients, who will be randomized to receive pemetrexed/cisplatin on day 1 and nintedanib or placebo on days 2 to 21, for a maximum of 6 cycles. Patients without disease progression who are eligible to continue study treatment will receive maintenance treatment with nintedanib or placebo until disease progression or undue toxicity. The primary end point is progression-free survival; OS is the key secondary end point. The study will use an adaptive design, including an interim analysis to reassess the number of OS events required to ensure sufficient power for OS analysis. The study is currently enrolling patients.