Relapsed or Refractory Multiple Myeloma
Conditions
Brief summary
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
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).
Interventions
COMBINATION_PRODUCTSVd (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)
COMBINATION_PRODUCTVd (Bortezomib+dexamethasone)
Vd Arm (\~50): Bortezomib (Cycles 1-8 \[BIW\], Cycles ≥ 9 \[QW\]) + dexamethasone (Cycles 1-8 \[Four times a week\], Cycles ≥ 9 \[BIW\])
Sponsors
Antengene Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | From date of randomization until the date of first documented PD (per IMWG criteria) or date of death, whichever occurs first. Participants without PD or death at the time of analysis are censored at the date of their last adequate disease assessment. | To evaluate progression-free survival |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | From randomization until the earlier of IRC-confirmed PD or start of subsequent anti-myeloma therapy, assessed up to 2 years. | evaluated by IRC (PR + VGPR + CR + sCR) |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORJin Lu, PhD
Peking University People's Hospital
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 61.8 years STANDARD_DEVIATION 8.07 |
| Body Mass Index (BMI) | 24.07 kg/m^2 STANDARD_DEVIATION 3.461 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 154 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 6 / 100 | 2 / 52 |
| other Total, other adverse events | 100 / 100 | 51 / 52 |
| serious Total, serious adverse events | 51 / 100 | 24 / 52 |
Outcome results
None listed