First-in-human, open-label, dose-finding, phase I trial, using a classical 3+3 design followed by a continual reassessment method (CRM).~Patients will be included in cohorts of a minimum of three or six patients to receive PM14 at successively increasing dose levels, starting at 0.25 mg/m^2 for the Days 1 and 8 schedule. For the Day 1 schedule, the starting dose will be 4.5 mg/m^2. Dose escalation will proceed only after all the patients fully evaluable for DLT included at one dose level have completed the first cycle (i.e., three weeks). Once the RD has been determined, expansion cohorts will be included to have a minimum of 20 fully evaluable patients per indication (tumor type) treated in the Expansion phase (regardless of the schedule administered), and thus have an adequate number of patients to assess safety. The indications of these patients will be chosen depending on the efficacy data obtained during dose escalation. Patients treated at the expansion cohorts will be evaluable by the Response Evaluation Criteria in Solid Tumors (RECIST v.1.1) and/or by serum markers only in patients with prostate cancer (prostate specific-antigen [PSA]) or ovarian cancer (carbohydrate antigen-125 [CA-125]) according to the Prostate-Specific Antigen Working Group Recommendations (PSAWGR) and the Gynecologic Cancer Intergroup (GCIG) specific criteria, respectively.
Despite recent advances in the treatment of solid tumors in general, advanced (metastatic) disease remains mostly incurable and there is an urgent need to develop new therapeutic options for these patients, particularly investigational drugs with novel mechanisms of action. The investigation of new combination regimens of non-crossresistant agents with acceptable-and not completely overlapping-toxicities has been a major way to improve response rate and outcome of patients with advanced solid tumors.