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) (BENCH)

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)

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Relapsed or Refractory Multiple Myeloma
• Intervention / Treatment: Combination product: SVd (Selinexor+Bortezomib+dexamethasone); Combination product: Vd (Bortezomib+dexamethasone)

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 Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230022
      • The First Affiliated Hospital of Anhui Medical University
    • Hefei, Anhui, China, 230031
      • The First Affiliated hospital of USTC
    • Wuhu, Anhui, China, 241001
      • The First Affiliated Hospital of Wannan Medical College
  • Beijing
    • Beijing, Beijing, China, 100044
      • Peking University People's Hospital
    • Beijing, Beijing, China, 100043
      • Beijing Chao-Yang Hospital
  • Chongqing
    • Chongqing, Chongqing, China, 400037
      • Xinqiao Hospital Army Medical University
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-sen University Cancer Center
    • Guangzhou, Guangdong, China, 510000
      • Guangdong Provincial People's Hospital
    • Shenzhen, Guangdong, China, 518035
      • Shenzhen Second People's Hospital
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital Central South University
    • Changsha, Hunan, China, 410013
      • The Third Xiangya Hospital of Central South University
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Jiangsu Province Hospital
    • Xuzhou, Jiangsu, China, 221000
      • The Affiliated Hospital of Xuzhou Medical University
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Affiliated Hospital of Nantong University
    • Nanchang, Jiangxi, China, 330006
      • The First Hospital of Nanchang
  • Liaoning
    • Shenyang, Liaoning, China, 110004
      • Shengjing Hospital China Medical University
  • Shandong
    • Jinan, Shandong, China, 250021
      • Shandong Provincial Hospital
    • Qingdao, Shandong, China, 266000
      • The Affiliated Hospital of Qingdao University
    • Qingdao, Shandong, China, v
      • Qingdao Municipal Hospital
  • Shangdong
    • Jinan, Shangdong, China, 250012
      • Qilu Hospital of Shangdong University
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Zhongshan Hospital Fudan University
    • Shanghai, Shanghai, China, 200025
      • Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine
    • Shanghai, Shanghai, China, 09022836
      • Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine
    • Shanghai, Shanghai, China, 200233
      • Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University
  • Sichuan
    • Chengdu, Sichuan, China, 610072
      • Sichuan Provincial People's Hospital
  • Tianjin
    • Tianjin, Tianjin, China, 300052
      • Tianjin Medical University General Hospital
    • Tianjin, Tianjin, China, 300060
      • Tianjin Medical University Cancer Institute & Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310016
      • Sir Run Run Shaw Hospital Zhejiang University of Medicine
    • Hanzhou, Zhejiang, China, 310003
      • The first Affiliated Hospital, Zhejiang University School of Medicine
    • Ningbo, Zhejiang, China, 315010
      • Ningbo First Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Understand and voluntarily sign an informed consent form (ICF).
2. Age ≥ 18 years.

3. Confirmed MM with measurable disease per IMWG guidelines, and meet at least 1 of the following:

   1. 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
   2. Urinary M-protein level ≥ 200 mg/24 hours; or
   3. Serum FLC ≥ 100 mg/L, provided that the serum FLC ratio is abnormal (Normal FLC ratio: 0.26 to 1.65).
4. 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.
5. Valid evidence of progressive MM (based on the Investigator's determination according to the IMWG response criteria) on or after their last regimen.
6. Must have an ECOG Status score of 0, 1, or 2.
7. Renal function should meet the following criteria: creatinine clearance [CrCl] rates ≥ 20 mL/min (Calculated using the formula of Cockroft and Gault).
8. 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.
9. 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:

1. Prior exposure to SINE compounds (Including ATG-010), or suspected allergy to SINE or similar drugs.
2. Active plasma cell leukemia.
3. Documented systemic light chain amyloidosis.
4. MM involving the central nervous system.
5. POEMS syndrome (Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes).
6. Spinal cord compression related to MM.
7. Greater than Grade 2 peripheral neuropathy or Grade ≥ 2 peripheral neuropathy with pain at baseline, regardless of whether the subject is currently receiving medication.
8. Known intolerance, hypersensitivity, or contraindication to glucocorticoids.
9. Active graft versus host disease (After allogeneic stem cell transplantation) at screening.
10. Uncontrolled active infections requiring intravenous antibiotics, antivirals, or antifungal therapy in 2 weeks prior to C1D1.
11. Major surgery within 4 weeks prior to C1D1.
12. Known active human immunodeficiency virus (HIV) infection or HIV seropositivity.
13. 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).
14. Pregnant or lactating women.
15. Life expectancy of < 4 months.
16. 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.
17. 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.
18. Contraindication to any of the required concomitant drugs or supportive treatments.
19. Any diseases or complications which may interfere with the study procedures.
20. Subject unwilling or unable to comply with the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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])

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	To evaluate progression-free survival	Three years after last patient first dose

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Antengene Corporation
• Investigators: Principal Investigator: Jin Lu, PhD, Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2021
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: June 17, 2021
• First Submitted That Met QC Criteria: June 17, 2021
• First Posted (Actual): June 25, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 10, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Enzyme Inhibitors; Bortezomib; Dexamethasone; Dexamethasone acetate; BB 1101
• Other Study ID Numbers: ATG-010-MM-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No