Contributions
Abstract: PB1670
Type: Publication Only
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
ATG-010 (Selinexor) 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 relapsed/refractory MM (RRMM) (NCT03944057).
Aims
To evaluate efficacy and safety of oral ATG-010 plus low dose dexamethasone in Chinese pts with RRMM.
Methods
Enrolled pts have been previously treated with and refractory to proteasome (PI), immunomodulatory agent (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).
Conclusion
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.
Keyword(s): Multiple myeloma, Oral, Refractory, Relapse
Abstract: PB1670
Type: Publication Only
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
ATG-010 (Selinexor) 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 relapsed/refractory MM (RRMM) (NCT03944057).
Aims
To evaluate efficacy and safety of oral ATG-010 plus low dose dexamethasone in Chinese pts with RRMM.
Methods
Enrolled pts have been previously treated with and refractory to proteasome (PI), immunomodulatory agent (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).
Conclusion
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.
Keyword(s): Multiple myeloma, Oral, Refractory, Relapse