Phase 2 March Study: ATG-010 Plus Low Dose Dexamethasone in Chinese Relapsed/Refractory Multiple Myeloma (RRMM) Patients Previously Treated with an Immunomodulatory Agent (IMiD) and a Proteasome Inhibitor (PI)

Background: ATG-010 (selinexor) is a novel, oral selective inhibitor of nuclear export, which blocks exportin 1. US FDA has approved selinexor plus low dose dexamethasone (Sd) to treat patients (pts) with penta-refractory MM based on the STORM study. MARCH is a single arm, Phase 2, registrational study to assess efficacy and safety of Sd in Chinese pts with RRMM. Methods: Enrolled Chinese pts were previously refractory to PI, IMiD, and last line of therapy. ATG-010 (80mg) plus dexamethasone (20mg) was administered twice weekly. The primary endpoint was overall response rate (ORR) per independent review committee. The planned 82 pts would provide ~80% power to test against null hypothesis (H 0) of 15% ORR at one-sided α of 0.025 at the primary analysis, which is presented here. Results: As of 6 th May 2021, 9 (11%) of the 82 pts were still on treatment. Median follow-up was 10.6 months (mo) (range: 2.3-19.6). Median age was 60 years (39% ≥ 65yrs). Median duration from MM initial diagnosis was 3.2 years. A total of 61 pts (74.4%) had cytogenetic abnormalities (del(17p): 22.0%), 18 (22.0%) with baseline plasmacytoma, and 18 (22.0%) with creatinine clearance < 60ml/min. Median number of prior regimens were 5 (range 1-16); 23 pts (28.0%) had received daratumumab (triple-class exposure), 20 pts were triple-class refractory (TCR), and10 pts (12.2%) had undergone CAR-T therapy. ORR was 29.3% (95% CI: 19.7, 40.4), rejecting H 0, including 4 VGPR (very good partial response). Median duration of response (DOR) was 4.7 mo, median progression free survival (PFS) was 3.7 mo, and median overall survival (OS) was 13.2 mo. Among 20 TCR pts, ORR was 25.0% (95% CI:8.7, 49.1), mDOR 10.2 mo, mPFS 2.9 mo, and mOS 11.9 mo. Efficacy was evident in elderly pts (≥ 65yrs), with ORR 25% (95% CI: 11.5, 43.4) and mPFS 2.8 mo. Median OS and DOR were not reached. Sd also demonstrated a similar response rate in pts with high-risk cytogenetic abnormalities, with an ORR of 24.6% (95% CI: 14.5, 37.3). Efficacy of Sd was generally consistent across cytogenetic risk subgroups, including del (17p) pts with ORR 22.2% (95% CI: 6.4, 47.6), mDOR 3.8mo, and mPFS 2.9 mo. The most common non-hematologic treatment-emergent adverse events (TEAEs) of any grade included nausea (78%), hyponatremia (67.1%), weight loss (65.9%), decreased appetite (62.2%), asthenia (59.8%)/fatigue (15.9%), and vomiting (50.0%). The most common grade≥3 non-hematologic TEAE were hyponatremia (29.3%), pneumonia (26.8%), hypokal