Abstract 1124P
Background
Selinexor is a first-in-class novel, oral potent selective inhibitor of nuclear export, which inhibits the transport protein Exportin-1. Preclinical models have suggested that SEL in combination with checkpoint inhibitor (CPI) would enhance the ability to inhibit the proliferation and survival of tumor cells.
Methods
This open label, single center phase IB combination therapy study in metastatic/locally advanced cancers enrolled either treatment naïve (t/n) pts or pts who relapsed on prior therapies (r/p). The addition of SEL to multiple standard chemotherapy and CPI regimens was tested in parallel, with ARM L using PEM (200g IV q3 weeks) in combination with SEL (starting dose 60mg PO BIW). For this melanoma (MM) cohort, we used recommended phase II dose (RP2D) data obtained from the dose escalation. Primary objective was to establish the safety and tolerability of SEL/PEM. Secondary endpoints included response rate (RR) and progression free survival (PFS).
Results
25 pts MM (13 male) have enrolled, including 6 pts with uveal MM, with a median age of 65.8 years (range 31.4-83). The majority of patients (n=17) had no prior systemic therapies for MM, but 5 pts had +/>3 lines of prior therapy. Most common SEL or PEM related AEs included nausea (68%), vomiting (52%), and anemia (48%). Three pts discontinued therapy due to AE. At a median follow up of 4.8 months (range 0.1-14.0) three pts achieved a CR (13%), 6 achieved a PR (26%) and 10 (43%) had stable disease (SD). Specifically, the overall RR in non-uveal t/n pts, 54% achieved either a CR (23%) or PR (31%). None of the uveal MM responded (5 pts SD). The median PFS for the entire cohort has not been reached and the 6-month PFS rate was 0.65 (95% CI: 0.46, 0.91). The 9-month PFS rate was 0.57 (95% CI: 0.37, 0.87). The median overall survival (OS) has not been reached, and the 6 months OS rate of 0.81 (95% CI: 0.63, 1). 22/25 pts are still alive.
Conclusions
The RP2D dose was Selinexor 60 mg po BIW and q 3 week PEM in patients with MM. Treatment with SEL/PEM is well-tolerated and shows significant clinical activity with a ORR of 54% compared to historical ORR of 30% with single agent PEM in t/n pts compared to historic single agent PEM. The combination warrants further evaluation.
Clinical trial identification
NCT02419495.
Editorial acknowledgement
Legal entity responsible for the study
University of Texas MD Anderson Cancer Center.
Funding
Karyopharm Therapeutics, Inc.
Disclosure
All authors have declared no conflicts of interest.