Results of the phase 2 MARCH Study: Oral ATG-010 (Selinexor) plus low dose dexamethasone in Chinese patients with relapsed/refractory multiple myeloma (RRMM) previously treated with an immunomodulatory agent (IMiD) and a proteasome inhibitor (PI).

Abstract

Listen

Translate article

e20002 Background: ATG-010 is a novel, oral selective inhibitor of nuclear export inhibiting exportin 1. 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) was approved by US FDA for treatment of patients (pts) with penta-refractory MM in 2019 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 pts have been previously treated with and refractory to PI, IMiD, and the last line of therapy. Sd is administered in 4-week cycles. Primary endpoint is overall response rate (ORR) per independent review committee. The total planned enrollment of 82 pts provides ̃80% power to test against H0 of 15% ORR at one-sided α of 0.025. This abstract provides data from a planned analysis of 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 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 DOR was 4.6 mo (95% CI: 1.42, NE). Median PFS was 3.7 mo (95% CI: 1.92, 4.66). Median OS was not reached; 9-mo OS rate was 68.5%. ORR was 33.3% in triple-class-exposed pts, and 44.4% in pts with prior CAR-T. ORR was generally consistent across subgroups. Common 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%), 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%), hyponatremia (3.3%). Eight pts (13.3%) had TEAEs leading to treatment discontinuation, including (> 2%): thrombocytopenia (5%) and pneumonia (3%). Three fatal TEAEs were pneumonia, intracranial hemorrhage and sudden death (1 each). Conclusions: In Chinese RRMM pts refractory to both IMiD and PI, with a highly unmet medical need, MARCH confirms the efficacy of Sd as a promising new oral therapeutic option with a manageable safety profile, which is consistent with STORM. Clinical trial information: NCT03944057.