A Multicenter Phase II Basket Clinical Trial of Lurbinectedin (PM01183) in Selected Advanced Solid Tumors.

TPS2604 Background: PM01183 (lurbinectedin) is a new anticancer drug that binds to the DNA minor groove and blocks trans-activated transcription, inducing formation of double-strand DNA breaks leading to cell apoptosis. COMPARE analysis revealed that lurbinectedin’s mechanism of action differs from the other 98 chemotherapy agents tested Advanced small cell lung cancer (SLCL), neuroendocrine tumors (NET), head and neck (H&N), biliary tract and endometrial carcinoma, BRCA1/2-associated metastatic breast cancer, carcinoma of unknown primary site, germinal cell tumors and Ewing family of tumors represent unmet medical needs. Cytotoxic chemotherapy remains a major component of their therapeutic armamentarium but new anticancer agents are needed to broaden clinical benefit. PM01183 has already shown clinical activity in BRCA1/2 breast cancer, SCLC, endometrial carcinoma, NET, H&N and in tumors with high proliferation index. This exploratory phase 2 trial has been designed to confirm the PM01183 anticancer activity, as a single agent, in several difficult-to-treat tumors. Methods: Primary objective: antitumor activity of PM01183 in terms of response rate by RECIST v.1.1, in the aforementioned indications. Secondary objectives: duration of response, clinical benefit, progression-free survival and 1-year overall survival in each tumor type. Pharmacokinetics, pharmacogenomic analyses of potential prognostic/predictive factors. Safety profile. Patients with each tumor type will be enrolled in nine cohorts. Up to 25 evaluable patients are planned to be recruited in each of them. To consider PM01183 active in the tumors analyzed, at least two confirmed responses in the 25 patients of each cohort are expected. If no responses are observed in the first 15 evaluable patients of each cohort, the accrual of this cohort will be stopped. If one confirmed response is observed in the first 15 evaluable patients, recruitment of this cohort will continue to 25 patients. Patients will receive PM01183 i.v. as a 1 hour infusion, every three weeks at a dose of 4 mg/m2. In patients with ECOG PS = 2 or > 70-years-old, dose will be 3 mg/m2. Twenty six centers in 8 countries participate in this trial.