Phase IB study to evaluate the safety of selinexor in combination with multiple standard chemotherapy agents in patients with advanced malignancies.

Abstract

TPS2603 Background: Selinexor is a first-in-class, slowly reversible, Selective Inhibitor of Nuclear Export (SINE) compound that specifically blocks XPO1. Inhibition of XPO1 results in nuclear localization, accumulation, and reactivation of tumor suppressor proteins, therefore selectively inducing apoptosis in cancer cells, while largely sparing normal cells. This unique property of XPO1 inhibition has been deployed as a novel therapeutic strategy with success in several solid tumors and hematologic malignancy clinical trials. Preclinical studies have shown that SINE compounds behave synergistically to enhance cancer cell death with combined with different therapeutic agents. This Phase I trial is based on such preclinical evidence. The primary objective of the study is to establish the safety and tolerability of selinexor when given in combination with thirteen standard chemotherapy regimens. The secondary objectives are to determine disease control and progression-free survival of patients receiving selinexor administered with standard chemotherapy treatments in specific tumor subsets. Methods: Adult patients ≥ 18 years of age are eligible if they have histologically confirmed neoplasms (excluding hematological malignancies and brain tumors) that are refractory to established therapy known to provide clinical benefit for their condition. Patients are required to have either measurable disease (RECIST 1.1) or evaluable disease, and an ECOG performance status of 0-1. Enrollment is ongoing for dose escalation with the plan for dose expansion as follows: Clinical trial information: NCT02419495. [Table: see text]