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)

Study Overview
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Brief Summary
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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).

Detailed Description
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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).

Official Title
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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)

Conditions
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Relapsed or Refractory Multiple Myeloma

Intervention / Treatment
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* Combination Product: SVd (Selinexor+Bortezomib+dexamethasone)
* Combination Product: Vd (Bortezomib+dexamethasone)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SVd (Selinexor+Bortezomib+dexamethasone)<br>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)<br>* 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)<br>|
| Experimental: Vd(Bortezomib+dexamethasone)<br>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)<br>* Vd Arm ( 50): Bortezomib (Cycles 1-8 [BIW], Cycles ≥ 9 [QW]) + dexamethasone (Cycles 1-8 [Four times a week], Cycles ≥ 9 [BIW])<br>|

What is the study measuring?
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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 |