1817TiP - SAKK 17/16 - Lurbinectedin monotherapy in patients with progressive malignant pleural mesothelioma: A multicenter, single-arm phase II trial

Abstract

Background: Unresectable malignant pleural mesothelioma (MPM) is treated with first-line platinum-based chemotherapy. Unfortunately, there is no standard second-line treatment for progressive patients. As widely available options like gemcitabine and vinorelbine provide only modest efficacy, progressive MPM poses an unmet medical need for further treatment strategies. Lurbinectedin (PM01183) is a novel compound, which covalently binds to the DNA minor groove, inducing double-strand breaks, as well as selectively reducing the tumor-associated macrophages. It has already been tested as monotherapy or in combination with chemotherapy in several Phase I-III trials in different tumor entities (including small cell lung cancer and ovarian cancer) with encouraging results. Based on MPM cases treated with lurbinectedin within the respective Phase I trials, where promising activity had been shown, we are currently conducting this proof-of-concept trial of safety and efficacy of lurbinectedin monotherapy in progressive MPM. Trial design: This is a prospective 2-stage single-arm multicenter phase II trial. MPM patients progressing after platinum-based chemotherapy with good performance status are eligible for the trial. Prior surgery and/or radiotherapy and pretreatment with immunotherapy are allowed. Treatment will be given with 3.2 mg/m2 lurbinectedin intravenously every 3 weeks (one cycle) until progression, unacceptable toxicity or patient withdrawal. Re-staging using contrast-enhanced computer tomography will be performed every 6 weeks. The primary endpoint of the trial is progression-free survival (PFS) at 12 weeks. Secondary endpoints are PFS, objective response rate, disease control rate at 12 weeks, overall survival, time-to-treatment failure and adverse events. A total of 6 Swiss and 3 Italian sites will participate for a total of 43 patients, as required by Simon’s two-stage design. Accrual has already begun in Switzerland, is expected for February 2018 in Italy, and is estimated to be completed by beginning of 2019. Up to now 11 patients have been treated within the trial. Clinical trial identification: NCT03213301. Legal entity responsible for the study: Swiss Group for Clinical Cancer Research (SAKK). Funding: SAKK, PharmaMar. Disclosure: All authors have declared no conflicts of interest.