P-211: Phase 2 MARCH study: ATG-010 plus 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), a novel, oral selective inhibitor of nuclear export, inhibits exportin1. In preclinical and clinical studies, ATG-010 has demonstrated activity against multiple myeloma (MM). ATG-010 (80 mg biweekly) plus dexamethasone (20 mg biweekly) (Sd) has been approved by US FDA for treatment of patients (pts) with penta-refractory MM based on the STORM study. MARCH is a single arm, Phase 2 study to assess efficacy and safety of Sd in Chinese pts with RRMM. Methods Enrolled Chinese pts were previously treated with and refractory to PI, IMiD, and the last line of therapy. Sd was administered in 4-week cycles. The primary endpoint was overall response rate (ORR) per independent review committee. The total planned 82 pts provide -80% power to test against H0 of 15% ORR at one-sided α of 0.025. This abstract includes data from the first 60 treated pts. Results As of 13 Oct 2020, 18 (30%) of the 60 pts were on treatment. Median follow-up was 9.5 months (mo) (range: 1.9-12.8). Median age was 61 years (range 43-82; 42% > 65). Pts had received a median of 5 (range 1-16) prior MM regimens, with the following baseline risk factors: 72% R-ISS II/III, 70% cytogenetic abnormalities, 22% del (17p13),20% renal impairment, 15% prior CAR-T therapy, and 25% pre-treated with daratumumab (considered ‘triple-class exposed’). ORR was 26.7% (95% CI: 16.1, 39.7). Median duration of response (DOR) was 4.6 mo (95% CI: 1.42, NE). Median progression free survival was 3.7 mo (95% CI: 1.92, 4.66). Median overall survival (OS) was not reached; 9-mo OS rate was 68.5%. ORR was 33.3% in triple-class-exposed pts. Nine pts had prior CAR-T therapy with a median of 9 prior regimens (range 5-12). Among them, ORR was 44.4%, and median DOR was 3 mo (95% CI; 0.96, 4.63). Common treatment emergent adverse events (TEAEs) of any grade included: thrombocytopenia (87%), nausea (87%), leukopenia (85%), anemia (85%), lymphopenia (78%), neutropenia (73%), weight loss (72%), hyponatremia (65%), decreased appetite (63%), asthenia (62%)/fatigue (17%), hyperglycemia (53%), vomiting (52%), hypocalcemia (38%), hypokalemia (30%), diarrhea (30%), and pneumonia (27%). Common TEAEs of Grade ≥ 3 included: anemia (60%), thrombocytopenia (55%), leukopenia (42%), lymphopenia (42%), neutropenia (38%), hyponatremia (28%), and pneumonia (23%). Thirty pts (50%) had TESAEs, including (>3%): thrombocytopenia (15%), pneumonia (15%), anemia (6.7%), and hyponatremia (3.3%). Eight pts (13.3%) had TEAEs leading to treatment discontinuation, including (>2%): thrombocytopenia (5%) and pneumonia (3%). There were three fatal TEAEs: pneumonia, intracranial hemorrhage, and sudden death (1 each). Conclusions MM pts refractory to both IMiD and PI remain a high unmet medical need. The MARCH study confirms the efficacy of Sd in Chinese patients with a manageable safety profile. These data are consistent with the STORM trial and offer a new, oral therapeutic option for MM patients.