Abstract 1331P
Background
Patients (pts) with NSCLC have few treatment options beyond 3 lines. RAS mutations (mut), found in 25% of NSCLC adenocarcinomas, are associated with poor response to conventional chemotherapy and poor clinical outcomes. SEL, an oral selective inhibitor of nuclear export (SINE), has shown synergy with taxane-based therapy in mouse models of prostate, breast and ovarian cancer. Preliminary clinical data (NCT03095612) have shown anti-tumor activity of SEL with DTX in pts with NSCLC with RAS mut treated with at least 1 prior regimen containing a checkpoint inhibitor.
Methods
This phase I/II, open-label study enrolled pts with metastatic NSCLC, regardless of RAS mut, that progressed after 1-2 lines of systemic therapy, including 1 line of an anti-PD1/L1 monoclonal antibody. Pts were treated using weekly oral SEL 60 mg and DTX 75 mg/m2 once every 3 weeks. Anti-tumor activity, safety and tolerability were assessed.
Results
Twelve pts (6 male), median age 70.5 years, RAS mut 50%, median no. of prior lines 1 (1-2) are enrolled. At data cutoff (28-APR-21) median treatment duration was 108 days (30-411) with 10 pts evaluable for response. Objective response rate was 20% with 2 partial responses (1 has NSCLC with RAS mut G12V, 1 with wild type [wt] RAS). Disease control rate was 100% with 8 pts with stable disease (4 have NSCLC with RAS mut, 2 with RAS wt, 2 with unknown RAS status). Two pts developed clinical progression (1 has NSCLC with RAS mut, 1 with RAS wt). Median progression-free survival (PFS) and overall survival have not been reached with median PFS follow-up of 17.3 and 18.1 weeks for RAS mut and wt, respectively. The most common TEAEs in >20% of patients are nausea (58%), fatigue, decreased appetite, diarrhea (50% each), asthenia (42%), vomiting, weight decrease, anemia, alopecia, back pain (33% each), pyrexia, peripheral edema (25%). Six pts (36%) had at least 1 serious TEAE.
Conclusions
Combined SEL with DTX demonstrated objective response and disease control in pts with progressive metastatic NSCLC. Therapy was well tolerated with no unanticipated AEs observed. Further investigation of SEL with DTX in NSCLC is warranted including in pts with NSCLC with RAS mut.
Clinical trial identification
NCT04256707.
Editorial acknowledgement
Legal entity responsible for the study
Karyopharm Therapeutics Inc.
Funding
Karyopharm Therapeutics Inc.
Disclosure
A. Zer: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Stocks/Shares: Nixio; Financial Interests, Institutional, Research Grant: BMS. A. Zick: Financial Interests, Institutional, Research Grant: Karyopharm Therapeutics; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Roche. E. Netiv: Financial Interests, Personal, Full or part-time Employment: Karyopharm Therapeutics. F. Yang: Financial Interests, Personal, Full or part-time Employment: Karyopharm Therapeutics. S. Sharoni: Financial Interests, Personal, Full or part-time Employment: Karyopharm Therapeutics. C. Meng: Financial Interests, Personal, Full or part-time Employment: Karyopharm Therapeutics. P. Duic: Financial Interests, Personal, Full or part-time Employment: Karyopharm Therapeutics. D. Michel: Financial Interests, Personal, Full or part-time Employment, 00001252: Karyopharm Therapeutics. E. Sbar: Financial Interests, Personal, Full or part-time Employment: Karyopharm Therapeutics. J. Shah: Financial Interests, Personal, Full or part-time Employment: Karyopharm Therapeutics. M.G. Kauffman: Financial Interests, Personal, Full or part-time Employment: Karyopharm Therapeutics. S. Shacham: Financial Interests, Personal, Full or part-time Employment: Karyopharm Therapeutics. T. Golan: Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Merck Sharp & Dohme; Financial Interests, Personal, Speaker’s Bureau: AbbVie; Financial Interests, Personal, Advisory Role: AbbVie; Financial Interests, Personal, Speaker’s Bureau: Boiling; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Teva. All other authors have declared no conflicts of interest.