Relapsed or Refractory Multiple Myeloma
Conditions
Brief summary
The purpose of this study is to evaluate how well IBI3003 works when compared with the investigator's choice regimen (DPd or PVd)
Detailed description
This study is an open, multicenter, randomized controlled phase III clinical trial aimed at evaluating the efficacy and safety of IBI3003 compared to the investigator's choice regimen (DPd or PVd) in participants with relapsed or refractory multiple myeloma who have previously received 1-4 lines of therapy and have been exposed to three classes of drugs (proteasome inhibitors, immunomodulators, and anti-CD38 monoclonal antibodies). The plan is to enroll approximately 255 participants, who will be randomly assigned to the experimental group and the control group in a 2:1 ratio. Approximately 170 participants in the experimental group will receive IBI3003 treatment, while about 85 participants in the control group will receive the investigator's choice of treatment (DPd or PVd). Participants in the experimental group can discontinue medication for observation after meeting the criteria for stopping treatment. During the discontinuation period, if they meet the re-treatment criteria, following discussion between the investigator and the sponsor, and based on the participant's preference, IBI3003 re-treatment may be given until the criteria for terminating treatment are met.
Interventions
DRUGPomalidomide Capsules
1. The DPd treatment regimen, one cycle every 28 days: Pomalidomide 4mg/d orally, on days 1-21; 2. The PVd treatment regimen, one cycle every 21 days: Pomalidomide 4 mg/d orally, on days 1-14 of each treatment cycle;
The PVd treatment regimen, with one cycle every 21 days: Bortezomib on days 1, 4, 8, and 11 of cycles 1-8, and on days 1 and 8 from cycle 9 onwards.
DRUGDaratumumab Injection (Subcutaneous Injection)
The DPd treatment regimen, one cycle every 28 days: on days 1, 8, 15, and 22 of cycles 1 and 2; on days 1 and 15 from cycles 3-6; and on day 1 from cycle 7 onwards.
DRUGIBI3003
According to body weight
Sponsors
Innovent Biologics (Suzhou) Co. Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
： 1. Age ≥18 years. 2. Documented initial diagnosis of multiple myeloma according to IMWG diagnostic criteria. 3. At least one of the following measurable disease indicators: * Serum M-protein ≥ 5 g/L（For IgA and IgD subtypes, it is recommended to use quantitative immunoglobulin measurements instead of M protein） * Urine M-protein ≥200 mg/24h * Serum free light chain (FLC) test: affected FLC level ≥100 mg/L and abnormal serum FLC ratio (\<0.26 or \>1.65) 4. Life expectancy ≥3 months. 5. Fertile females and sexually active fertile males must agree to use highly effective contraception (failure rate \<1% per year) during the study and for 90 days after the last dose of the investigational drug. For participants in the clinical trial, contraceptive measures must comply with local regulations regarding the use of contraceptive methods. Females and males must agree not to donate eggs (ova, oocytes) or sperm during the study and for 90 days after the last dose of the investigational drug. 6. Willing and able to comply with the prohibitions and restrictions specified in this protocol.
Exclusion criteria
： 1. Previous treatment with any BCMA-targeted therapy and any GPRC5D-targeted therapy. Patients who have received either BCMA-targeted or GPRC5D-targeted therapy are allowed to participate in the study. 2. Known active CNS involvement or exhibits clinical signs of meningeal involvement of multiple myeloma. 3. Spinal cord compression that leads to limited self-care ability occurs within six months prior to informed consent or is expected to occur in the near future. 4. Have history of primary immunodeficiency. 5. Have history of organ transplantation. 6. Have received allogeneic hematopoietic stem cell transplantation within 6 months before the first administration of the study drug, or have received autologous stem cell transplantation within 3 months before the first administration of the study drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PFS assessed by independent review committee | up to 24 months after the last enrolled participant receives the first dose of study drug | PFS is defined as the duration from the date of randomization to either PD or death, whichever comes first. Disease progression will be determined according to the IMWG response criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS assessed by investigator | up to 24 months after the last enrolled participant receives the first dose of study drug | PFS is defined as the duration from the date of randomization to either PD or death, whichever comes first. Disease progression will be determined according to the IMWG response criteria |
| Negativity rate of minimal residual disease (MRD) | up to 24 months after the last enrolled participant receives the first dose of study drug | Defined as the proportion of participants achieving MRD-negative status |
| Sustained MRD negativity rate | up to 24 months after the last enrolled participant receives the first dose of study drug | Defined as the proportion of participants achieving MRD-negative status and maintaining it for at least 1 year |
| 6-month MRD negativity rate. | up to 24 months after the last enrolled participant receives the first dose of study drug | The proportion of participants achieving a response of CR or better and MRD-negative status at 6 months post-randomization |
| 12-month MRD negativity rate | up to 24 months after the last enrolled participant receives the first dose of study drug | The proportion of participants achieving a response of CR or better and MRD-negative status at 12 months post-randomization |
| Objective response rate | up to 24 months after the last enrolled participant receives the first dose of study drug | Objective response rate is defined as the percentage of participants who achieve PR or better prior to subsequent antimyeloma therapy in accordance with the IMWG criteria |
| Complete response or better rate | up to 24 months after the last enrolled participant receives the first dose of study drug | Complete response or better rate is defined as the percentage of participants who achieve CR or better prior to subsequent antimyeloma therapy in accordance with the IMWG criteria |
| Very good partial response or better rate | up to 24 months after the last enrolled participant receives the first dose of study drug | Very good partial response or better rate is defined as the percentage of participants who achieve very good partial response or better prior to subsequent antimyeloma therapy in accordance with the IMWG criteria |
| Duration of response | up to 24 months after the last enrolled participant receives the first dose of study drug | DoR is defined as the time interval between the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease according to the IMWG response criteria or death due to any cause, whichever occurs first |
| Time to response | up to 24 months after the last enrolled participant receives the first dose of study drug | Defined as the time from randomization to the date of the first tumor response assessment of PR or better among participants with a best overall response of PR or better |
| Time to best response | up to 24 months after the last enrolled participant receives the first dose of study drug | Defined as the time from randomization to the date of first documented Best Overall Response (BOR) among participants with a best overall response of PR or better |
| Time to next treatment | up to 24 months after the last enrolled participant receives the first dose of study drug | Defined as the time from initiation of study drug treatment to initiation of next-line therapy |
| Overall survival | up to 24 months after the last enrolled participant receives the first dose of study drug | OS is defined as the time from the date of randomization to the date of the participant's death due to any cause |
| Number of Participants with Treatment-Emergent Adverse events (TEAE) by Severity | up to 24 months after the last enrolled participant receives the first dose of study drug | Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Grading of Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) according to the ASTCT consensus |
| Number of Participants with Treatment-related Adverse Event (TRAE) by Severity | up to 24 months after the last enrolled participant receives the first dose of study drug | Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Grading of Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) according to the ASTCT consensus |
| Number of Participants with Adverse Event of Special Interest (AESI) by Severity | up to 24 months after the last enrolled participant receives the first dose of study drug | Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Grading of Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) according to the ASTCT consensus |
| Number of Participants with Serious Adverse Event (SAE) | up to 24 months after the last enrolled participant receives the first dose of study drug | Defined as the percentage of participants with SAE |
| Percentage of Participants With Meaningful Improvement in HRQoL, Symptoms and Functioning Using the EORTC-QLQ-C30 Scale Scores | up to 24 months after the last enrolled participant receives the first dose of study drug | Percentage of participants with meaningful improvement in symptoms, functioning, and HRQoL as assessed by EORTC-QLQ-C30 score will be reported |
| Percentage of Participants With Meaningful Improvement in HRQoL, Symptoms and Functioning Using the MySIm-Q Scale Scores | up to 24 months after the last enrolled participant receives the first dose of study drug | Percentage of participants with meaningful improvement in symptoms, functioning, and HRQoL as assessed by MySIm-Q score will be reported |
Countries
China
Contacts
CONTACTHaiyan Zhu
Outcome results
None listed