1843OSAKK 17/16 - Lurbinectedin as second or third line palliative chemotherapy in malignant pleural mesothelioma (MPM): A multi-center, single-arm phase II trial

Abstract Background Available systemic 2nd or 3rd line options for MPM show a median progression-free survival (mPFS) of less than 2 months (mo) and median overall-survival (mOS) of 6-9 mo. Lurbinectedin (PharmaMar) is a novel compound with a dual role of binding to the DNA minor groove and inhibiting cytokine transcription of tumor-associated macrophages. Single MPM pts treated with lurbinectedin in early clinical trials showed encouraging outcome. The aim of current trial was to provide further data on safety and efficacy of lurbinectedin in progressive MPM. Methods MPM pts (all histologies) not amenable for local treatment and progressing after first-line platinum-pemetrexed chemotherapy +/- immunotherapy (IO) received 2nd or respectively 3rd line lurbinectedin. Lurbinectedin 3.2 mg/m2 every 3 weeks was given i.v. until progression or unacceptable toxicity. Primary endpoint was PFS at 12 weeks (PFS12wks) and would be met if achieved by at least 21 pts (p0 ≤ 35%; mPFS 2 mo). Secondary endpoints were mPFS, mOS and adverse events (AEs). Results 6 Swiss and 3 Italian centers recruited 42 pts (33 epithelioid, 4 biphasic, 5 sarcomatoid). 10/42 (23.8%) pts also received prior IO. At cut-off date (31st January 2019) PFS12wks was met by 22/42 pts (52.4%; 95%CI [38.7%; 63.5%]; p = 0.015) for mPFS of 4.1mo (95% CI [2.6; 5.5]) and mOS of 11.9mo (95% CI [9.2; 14.7]). 1 pt had complete, 1 pt partial response and 20 pts stable disease as best response. No significant difference in PFS12wks, mPFS and mOS was observed in epithelioid vs non-epithelioid MPM and prior-IO vs non-prior IO pts. All pts experienced AEs. Grade 3-4 toxicity was seen in 33 pts with most common being leuco-/lymphopenia (60.6%) and fatigue (24.2%). Febrile neutropenia was 9.1%. No pt discontinued treatment due to toxicity. Conclusions The primary efficacy endpoint was reached with acceptable toxicity. Lurbinectedin showed promising activity compared to historical data. Neither histology nor prior IO seems to affect efficacy of lurbinectedin, but respective pts numbers are small for definitive conclusions. Further evaluation of lurbinectedin in a large randomized trial is warranted. Clinical trial identification NCT03213301. Legal entity responsible for the study Swiss Group for Clinical Cancer Research. Funding PharmaMar; State Secretariat for Education, Research and Innovation (SERI). Disclosure Y. Metaxas: Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre