Phase I study to evaluate the tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) of PM01183 (Lurbinectedin) in combination with olaparib in patients with advanced solid tumors.

5573Background: PM01183 (Lurbinectedin) is a new anticancer drug that exerts antitumor activity through inhibition of trans-activated transcription and modulation of tumor microenvironment and is highly active in platinum resistant ovarian cancer. (Poveda A et al. ASCO 2014.abstr #5505). Olaparib (AZD2281, KU-0059436) is a polyadenosine 5’diphosphoribose (poly [ADP ribose]) polymerase (PARP) inhibitor of PARP-1,-2 and-3 with proven antitumoral activity in homologous recombination deficient tumors. The combination of PM01183 and Olaparib has shown synergistic activity in cell-lines, independent of BRCA mutation status. Methods: This phase I study evaluates the safety, PK and PD of PM1183 in combination with short course of Olaparib tablet formulation [days (d) 1-5] a cycle of 21 d, through a 3+3 dose escalation design (NCT02684318) Patients with advanced or metastatic solid tumors without established standard therapeutic alternatives were selected. Primary endpoints: safety (MTD, DLT and RP2D). Secondary e...