1818TiPMulticentre, double-blind, randomised phase II study evaluating gemcitabine with or without ramucirumab as II line treatment for MPM

Background: Malignant Pleural Mesothelioma (MPM) is still a fatal cancer and median overall survival is still approximately 1 year after diagnosis and new therapies are being awaited. After first line therapy patients inevitably progress and usually they are in good conditions and inquire about a second-line treatment. Even if a second line therapy is frequently considered in common clinical practice, the optimal treatment has not been defined yet. Gemcitabine was largely used in association with platinum compounds before the registration of platinum-pemetrexed doublet in first line setting. Pre-clinical data suggest the importance of angiogenesis in tumour biology of MPM. Considering the documented high VEGFR-2 expression in MPM and the high affinity of ramucirumab for the same receptor, and given the failure of previous anti-angiogenetic drugs as single agent, we hypothesised a significant activity of ramucirumab in MPM in association with gemcitabine. Trial design: RAMES is a multicentre, double-blind, randomised Phase 2 study,to evaluate the efficacy and the safety of the addition of ramucirumab to gemcitabine as the second-line treatment of patients with MPM.Randomisation will be done via a centralized system and will stratified by performance status (0-1 vs 2) age (≤70 vs > 70) histology (epithlioid vs others) and time to progression after first line therapy (< 6 months vs ≥ 6 months).The primary objective is overall survival. Secondary objectives are progression free survival and safety. Patients will be randomly assigned (1:1) to receive intravenous gemcitabine (1000 mg/mq) on days 1 and 8 every 21 days with placebo or combined with intravenous ramucirumab 10 mg/kg (ramucirumab group) on day 1 of a 21-day cycle until progression disease or unacceptable toxicity. The interim analysis was performed 6 weeks after enrolment of the 80th patient. Blood samples were collected for pharmacokinetic and immunogenic analyses. The study duration will be 24 months for the accrual. The great amount of interest and the scarce availability of ongoing trials have made recruitment rapid. This will allow information on the possible benefit of ramucirumab in MPM to be given much earlier than expected. Clinical trial identification: EudraCT: 2016-001132-36. Legal entity responsible for the study: AUSL-IRCCS Reggio Emilia. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.