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)

Antengene

Status and phase: Active, not recruiting; Phase 3

Conditions: Relapsed or Refractory Multiple Myeloma

Treatments: Combination Product: Vd (Bortezomib+dexamethasone); Combination Product: SVd (Selinexor+Bortezomib+dexamethasone)

Study type: Interventional

Funder types: Industry

Identifiers

NCT04939142

ATG-010-MM-002

Details and patient eligibility

About

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).

Full 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).

Enrollment: 150 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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150 participants in 2 patient groups

SVd (Selinexor+Bortezomib+dexamethasone)

Experimental group

Description:

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.

Treatment:

Combination Product: SVd (Selinexor+Bortezomib+dexamethasone)

Vd(Bortezomib+dexamethasone)

Experimental group

Description:

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

Treatment:

Combination Product: Vd (Bortezomib+dexamethasone)