431P - Phase Ib study of safety and tolerability of selinexor in Asian patients with advanced solid cancers

Abstract

Background: Selinexor (SEL) is a potent Exportin 1 inhibitor that forces nuclear retention and activation of multiple tumour suppressor proteins resulting in tumour cell death. The safety, tolerability and pharmacokinetics were previously evaluated in the Asian population with preliminary evidence suggesting improved outcomes in tumors driven by the PI3K/AKT and Raf1/MEK/ERK pathway, thymic, NPC and refractory lymphoma. Methods: SEL was administered orally to patients with advance solid tumour malignancy with PI3K/AKT/RAS mutations, thymic carcinoma, NPC or double expressor/ transformed B cell lymphoma or cutaneous T-cell lymphoma in a phase Ib dose expansion study. Patients (pts) were treated using the established RP2D for Asian population of 60mg twice a week for 2 weeks in a 21-day cycle. Response was evaluated every two cycles (RECIST v1.1). Results: 47 pts (17 M/ 16 F) received 60mg oral SEL. 28, 1 and 4 pts with solid tumours with PI3K/AKT/RAS mutation, NPC and refractory lymphoma respectively were enrolled. 1 lung, 14 colorectal (CRC), 5 gynecological (1 cervix; 4 ovarian), 6 pancreatic and 2 breast respectively had mutations in the PI3K/AKT/RAS pathway. Median PFS for patients with solid malignancy with mutations in the PI3K/AKT/RAS pathway and refractory lymphoma was 40d and 81d respectively, with 1 lymphoma pt still ongoing after 441 days. Median PFS for pts with KRAS mutant CRC and pancreatic cancer was 42 and 31 days respectively. Dose reductions occurred in 7 (14.9%) pts and dose interruptions occurred in 29.8% of pts. Conclusions: The RP2D dose of SEL is tolerable and safe in the Asian population. This dose will be used in the phase 2 study for further efficacy analysis. Legal entity responsible for the study: The National Medical Research Council, Singapore. Funding: The National Medical Research Council, Singapore. Disclosure: All authors have declared no conflicts of interest.