BENCH: A Study of Evaluating the Safety and Efficacy of ATG-010, Bortezomib, and Dexamethasone (SVd) Versus Bortezomib and Dexamethasone (Vd) in Patients With Relapsed or Refractory Multiple Myeloma (RRMM)

Sponsor

Antengene Corporation (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04939142

Collaborator

(none)

150

Enrollment

Locations

Arms

38.5

Anticipated Duration (Months)

4.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Condition or Disease	Intervention/Treatment	Phase
Relapsed or Refractory Multiple Myeloma	Combination Product: SVd (Selinexor+Bortezomib+dexamethasone) Combination Product: Vd (Bortezomib+dexamethasone)	Phase 3

Detailed Description

This is a Phase III Randomized, Controlled, Multicenter, Open-label Study of ATG-010, Bortezomib, and Dexamethasone (SVd) Versus Bortezomib and Dexamethasone (Vd) in Patients with Relapsed or Refractory Multiple Myeloma (RRMM). About 150 subjects are planned to be enrolled in this study, and be randomized into two treatment Arms in a 2:1 allocation (SVd Arm or Vd Arm).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase III Randomized, Controlled, Multicenter, Open-label Study of ATG-010, Bortezomib, and Dexamethasone (SVd) Versus Bortezomib and Dexamethasone (Vd) in Patients With Relapsed or Refractory Multiple Myeloma (RRMM)

Actual Study Start Date :

Jul 30, 2021

Anticipated Primary Completion Date :

Jul 15, 2024

Anticipated Study Completion Date :

Oct 15, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SVd (Selinexor+Bortezomib+dexamethasone) Enrolled patients will be treated with ATG-010( 100 mg/QW, oral ) with Bortezomib( 1.3 mg/QW, hypodermic injection ) +dexamethasone ( 20 mg/QW, oral ) about 13.5cycles.	Combination Product: SVd (Selinexor+Bortezomib+dexamethasone) Randomized into two treatment Arms in a 2:1 allocation (SVd Arm or Vd Arm): (1) SVd Arm (~100): ATG-010 + (Once a week, QW) + bortezomib (QW) + dexamethasone (BIW)
Experimental: Vd(Bortezomib+dexamethasone) Enrolled patients will be treated with Bortezomib( 1.3 mg/QW, hypodermic injection ) +dexamethasone ( 20 mg/QW, oral ) about 13.5 cycles.	Combination Product: Vd (Bortezomib+dexamethasone) Vd Arm (~50): Bortezomib (Cycles 1-8 [BIW], Cycles ≥ 9 [QW]) + dexamethasone (Cycles 1-8 [Four times a week], Cycles ≥ 9 [BIW])

Arm

Intervention/Treatment

Experimental: SVd (Selinexor+Bortezomib+dexamethasone)

Enrolled patients will be treated with ATG-010( 100 mg/QW, oral ) with Bortezomib( 1.3 mg/QW, hypodermic injection ) +dexamethasone ( 20 mg/QW, oral ) about 13.5cycles.

Combination Product: SVd (Selinexor+Bortezomib+dexamethasone)

Randomized into two treatment Arms in a 2:1 allocation (SVd Arm or Vd Arm): (1) SVd Arm (~100): ATG-010 + (Once a week, QW) + bortezomib (QW) + dexamethasone (BIW)

Experimental: Vd(Bortezomib+dexamethasone)

Enrolled patients will be treated with Bortezomib( 1.3 mg/QW, hypodermic injection ) +dexamethasone ( 20 mg/QW, oral ) about 13.5 cycles.

Combination Product: Vd (Bortezomib+dexamethasone)

Vd Arm (~50): Bortezomib (Cycles 1-8 [BIW], Cycles ≥ 9 [QW]) + dexamethasone (Cycles 1-8 [Four times a week], Cycles ≥ 9 [BIW])

Outcome Measures

Primary Outcome Measures

Progression-Free Survival (PFS) [Three years after last patient first dose]
To evaluate progression-free survival

Secondary Outcome Measures

Overall Survival (OS) [Three years after last patient first dose]
The estimates of Kaplan-Meier
Duration of Response (DOR) [Three years after last patient first dose]
To evaluate duration of response
Objective response rate (ORR) [Three years after last patient first dose]
evaluated by IRC (PR + VGPR + CR + sCR)
Progression-free survival(PFS2) [Three years after last patient first dose]
PFS after further treatment followed by treatment with SVd/Vd
Time to remission(TTR) [Three years after last patient first dose]
To compare the efficacy of treatment with SVd and Vd
VGPR+CR+sCR [Three years after last patient first dose]
Proportion of subjects of VGPR + CR + sCR
Safety Endpoints [Three years after last patient first dose]
Incidence of any Grade ≥ 2 peripheral neuropathy events

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Understand and voluntarily sign an informed consent form (ICF).
Age ≥ 18 years.
Confirmed MM with measurable disease per IMWG guidelines, and meet at least 1 of the following:
Serum M-protein ≥ 0.5 g/dL (> 5 g/L) by serum protein electrophoresis (SPEP) or for immunoglobulin IgA, IgD myeloma, replaced by quantitative serum IgA, IgD levels; or
Urinary M-protein level ≥ 200 mg/24 hours; or
Serum FLC ≥ 100 mg/L, provided that the serum FLC ratio is abnormal (Normal FLC ratio: 0.26 to 1.65).
Had at least 1 prior anti-MM regimen and no more than 3 prior anti-MM regimens. Induction therapy followed by stem cell transplant and consolidation/maintenance therapy will be considered as 1 anti-MM regimen.
Valid evidence of progressive MM (based on the Investigator's determination according to the IMWG response criteria) on or after their last regimen.
Must have an ECOG Status score of 0, 1, or 2.
Renal function should meet the following criteria: creatinine clearance [CrCl] rates ≥ 20 mL/min (Calculated using the formula of Cockroft and Gault).
Resolution of any clinically significant non-hematological toxicities (If any) from previous treatments to Grade ≤1 or baseline by C1D1. Subject with chronic, stable Grade 2 non hematological toxicities may be included following approval from the Medical Monitor.
Female subjects of childbearing potential must have a negative serum pregnancy test at Screening. Female subjects of childbearing potential and fertile male subjects must use highly effective methods of contraception throughout the study and for 3 months following the last dose of study treatment.

Exclusion Criteria:

Prior exposure to SINE compounds (Including ATG-010), or suspected allergy to SINE or similar drugs.
Active plasma cell leukemia.
Documented systemic light chain amyloidosis.
MM involving the central nervous system.
POEMS syndrome (Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes).
Spinal cord compression related to MM.
Greater than Grade 2 peripheral neuropathy or Grade ≥ 2 peripheral neuropathy with pain at baseline, regardless of whether the subject is currently receiving medication.
Known intolerance, hypersensitivity, or contraindication to glucocorticoids.
Active graft versus host disease (After allogeneic stem cell transplantation) at screening.
Uncontrolled active infections requiring intravenous antibiotics, antivirals, or antifungal therapy in 2 weeks prior to C1D1.
Major surgery within 4 weeks prior to C1D1.
Known active human immunodeficiency virus (HIV) infection or HIV seropositivity.
Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus ribonucleic acid (RNA) or hepatitis B virus deoxyribonucleic acid (HBV-DNA).
Pregnant or lactating women.
Life expectancy of < 4 months.
Any active gastrointestinal dysfunction interfering with the subject's ability to swallow tablets, or any active gastrointestinal dysfunction that could interfere with absorption of study treatment.
Any active, serious psychiatric, medical, or other conditions/situations that, in the opinion of the Investigator, could interfere with treatment, compliance, or the ability to give informed consent.
Contraindication to any of the required concomitant drugs or supportive treatments.
Any diseases or complications which may interfere with the study procedures.
Subject unwilling or unable to comply with the protocol.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The First Affiliated Hospital of Anhui Medical University	Hefei	Anhui	China	230022
2	The First Affilate Hospital OF USTC	Hefei	Anhui	China	230031
3	The First Affiliated Hospital of Wannan Medical College	Wuhu	Anhui	China	241001
4	Beijing Chao-Yang Hospital	Beijing	Beijing	China	100043
5	Peking University People'S Hospital	Beijing	Beijing	China	100044
6	Xinqiao Hospital Army Medical University	Chongqing	Chongqing	China	400037
7	Guangdong Provincial People'S Hospital	Guangzhou	Guangdong	China	510000
8	Sun Yat-Sen University Cancer Center	Guangzhou	Guangdong	China	510060
9	Nanfang Hospital	Guangzhou	Guangdong	China	510515
10	Shenzhen Second People'S Hospital	Shenzhen	Guangdong	China	518035
11	Henan Cancer Hospital	Zhengzhou	Henan	China	450008
12	Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology	Wuhan	Hubei	China	430030
13	Xiangya Hospital Central South University	Changsha	Hunan	China	410008
14	The Third Xiangya Hospital of Central South University	Changsha	Hunan	China	410013
15	Jiangsu Province Hospital	Nanjing	Jiangsu	China	210029
16	The Affiliated Hospital of Xuzhou Medical University	Xuzhou	Jiangsu	China	221000
17	Affiliated Hospital of Nantong University	Nanchang	Jiangxi	China	330006
18	The First Hospital of Nanchang	Nanchang	Jiangxi	China	330006
19	Shengjing Hospital China Medical University	Shenyang	Liaoning	China	110004
20	The Affiliated Hospital of Qingdao University	Qingdao	Shandong	China	266000
21	Qingdao Municipal Hospital	Qingdao	Shandong	China	v
22	Qilu Hospital of Shangdong University	Jinan	Shangdong	China	250012
23	Shandong Provincial Hospital	Jinan	Shangdong	China	250021
24	Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai	China	09022836
25	Shanghai Changzheng Hospital	Shanghai	Shanghai	China	200003
26	Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai	China	200025
27	Zhongshan Hospital Fudan University	Shanghai	Shanghai	China	200032
28	Shanghai Sixth People's Hospital Affiliated to Shanghai JiaoTong University	Shanghai	Shanghai	China	200233
29	Sichuan Provincial People's Hospital	Chengdu	Sichuan	China	610072
30	Tianjin Medical University General Hospital	Tianjin	Tianjin	China	300052
31	Tianjin Medical University Cancer Institute & Hospital	Tianjin	Tianjin	China	300060
32	Sir Run Run Shaw Hospital Zhejiang University of Medicine	Hangzhou	Zhejiang	China	310016
33	The First Affiliated Hospital, Zhejiang University School of Medicine	Hanzhou	Zhejiang	China	310003
34	Ningbo First Hospital	Ningbo	Zhejiang	China	315010