PHASE 2 MARCH STUDY OF ORAL ATG-010 PLUS LOW DOSE DEXAMETHASONE IN CHINESE PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA PREVIOUSLY EXPOSED TO AN IMMUNOMODULATORY AGENT AND A PROTEASOME INHIBITOR
Author(s): ,
Weijun Fu
Affiliations:
Shangai Changzheng Hospital,Shanghai,China
,
Zhongjun Xia
Affiliations:
Sun Yat-sen University Cancer Center,Guangzhou,China
,
Chengcheng Fu
Affiliations:
The First Affiliated Hospital of Soochow University,Suzhou,China
,
Wenming Chen
Affiliations:
Beijing Chao-Yang Hospital,Beijing,China
,
Gang An
Affiliations:
Institute of Hematology and Blood Diseases Hospital,Tianjin,China
,
Zhen Cai
Affiliations:
The First Affiliated Hospital, College of Medicine, Zhejiang University,Hangzhou,China
,
Baijun Fang
Affiliations:
Henan Cancer Hospital,Zhengzhou,China
,
Hongmei Jing
Affiliations:
Peking University Third Hospital,Beijing,China
,
Yongqiang Wei
Affiliations:
Nanfang Hospital, Southern Medical University,Guangzhou,China
,
Jianyu Weng
Affiliations:
Guangdong Provincial People's Hospital,Guangzhou,China
,
Chunkang Chang
Affiliations:
Shanghai Jiao Tong University Affiliated Sixth People's Hospital,Shanghai,China
,
Lijuan Chen
Affiliations:
Jiangsu Province Hospital, First Affiliated Hospital of Nanjing Medical University,Nanjing,China
,
Sujun Gao
Affiliations:
the First Affiliated Hospital of Jilin University,Changchun,China
,
Xiequn Chen
Affiliations:
Xi Jing Hospital affiliated to the Fourth Military Medical University,Xi'An,China
,
Fei Li
Affiliations:
the First Affiliated Hospital of Nanchang University,Nanchang,China
,
Zhuogang Liu
Affiliations:
Shengjing Hospital of China Medical University,Shenyang,China
,
Jing Liu
Affiliations:
the Third Xiangya Hospital of Central South University,Changsha,China
,
Ying Jiao
Affiliations:
Antengene Therapeutics Ltd. ,Beijing,China
,
Aihua Wang
Affiliations:
Antengene Therapeutics Ltd. ,Shanghai,China
,
Zhinuan Yu
Affiliations:
Antengene Therapeutics Ltd. ,Shanghai,China
Lugui Qiu
Affiliations:
Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science and Peking Union Medical College,Tianjin ,China
EHA Library. Fu W. 06/09/21; 324343; PB1670
Weijun Fu
Weijun Fu
Contributions
Abstract

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

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