A First-in-human, Open-label, Phase 1 Study to Evaluate the Safety, Antitumor Activity, Pharmacokinetics, and Pharmacodynamics of Subcutaneous SAR446523, an Anti-GPRC5D ADCC-enhanced Monoclonal Antibody, in Participants With Relapsed/Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- Sanofi
- 入组人数
- 82
- 试验地点
- 18
- 主要终点
- Incidence of Dose Limiting Toxicities (DLTs)- Dose escalation (Part A)
研究概览
简要总结
This is a first-in-human study of SAR446523 conducted in patients with RRMM.
The study consists of two parts:
Dose escalation (Part A): In this part, up to 6 dose levels (DLs) of SAR446523 will be explored to determine the maximum administered dose (MAD), maximum tolerated dose (MTD), and recommended dose range (RDR) of 2 dose regimens which will be tested in the dose optimization part.
Dose optimization (Part B): In this part, participants will be randomly assigned in a 1:1 ratio using interactive response technology (IRT) to either one of the chosen dose regimens of SAR446523 (determined from data coming from Part A), to determine the optimal dose as the recommended phase 2 dose (RP2D) of SAR446523.
详细描述
The study will be considered ongoing until the last participant last visit has occurred. Participants will be allowed to continue therapy until disease progression, unacceptable AEs, participant or Investigator's request to discontinue treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with a documented diagnosis of multiple myeloma (MM) with measurable disease.
- •Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- •Dose escalation (Part A)
- •Participants must have received at least 3 prior lines of antimyeloma therapy, and must be either relapsed or refractory to the above therapies, or are intolerant to them.
- •Note: In Part A, prior exposure to anti g-protein-coupled receptor, class c, group 5, member d (GPRC5D) therapy and anti B-cell maturation antigen (BCMA) therapy is allowed.
- •Dose optimization (Part B)
- •Participants must have received at least 3 prior lines of antimyeloma therapy and be either relapsed or refractory to immunomodulator (IMiD), proteasome inhibitor (PI), anti CD38 monoclonal antibody (mAb), and anti BCMA targeting agent or are intolerant to them.
- •Note: In Part B, prior exposure to antiGPRC5D therapy is not allowed.
排除标准
- •Participants are excluded from the study if any of the following criteria apply: Eastern cooperative oncology group performance status (ECOG PS) of 2 or greater.
- •Primary systemic and localized amyloid light chain (AL) amyloidosis, active polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes (POEMS) syndrome, active plasma cell leukemia. Participants with central nervous system involvement or with clinical signs of meningeal involvement of multiple myeloma.
- •Systemic antimyeloma treatment within 14 days before the first study treatment administration.
- •Prior treatment with natural killer (NK)-cell engaging therapy (such as monoclonal antibody with antibody-dependent cellular cytotoxicity as primary mechanism of action) within 90 days of the first study treatment administration.
- •Inadequate organ and marrow function.
- •Participants with significant concomitant illness.
- •The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.
研究组 & 干预措施
Part A (Dose escalation)
Participants will receive SAR446523
干预措施: SAR446523 (Drug)
Part B Dose-1 (Dose optimization)
Participants will receive SAR446523 Dose-1
干预措施: SAR446523 (Drug)
Part B Dose-2 (Dose optimization)
Participants will receive SAR446523 Dose-2
干预措施: SAR446523 (Drug)
结局指标
主要结局
Incidence of Dose Limiting Toxicities (DLTs)- Dose escalation (Part A)
时间窗: Cycle 1 (28 days)
The incidence of DLTs will be evaluated using NCI CTCAE version 5.0 criteria.
Overall response rate (ORR) - Dose optimization (Part B)
时间窗: 24 months after the Last Participant In (LPI)
ORR is defined as the proportion of participants with sCR, CR, VGPR, and PR assessed as per Investigator according to the 2016 IMWG response criteria.
次要结局
- Number of participants with treatment emergent adverse events (TEAEs), injection related reactions (IRRs), injection site reactions (ISRs), serious adverse events (SAEs), adverse event of special interests (AESIs)(From the signing of informed consent to 30 days after the date of the last study treatment administration i.e., approximately 5 years)
- Change from baseline in laboratory abnormalities(From the signing of informed consent to 30 days after the date of the last study treatment administration i.e., approximately 5 years)
- ORR- Dose escalation (Part A)(24 months after the Last Participant In (LPI))
- VGPR or better rate(24 months after the Last Participant In (LPI))
- Clinical benefit rate (CBR)(24 months after the Last Participant In (LPI))
- Number of participants with symptomatic AEs -Part B(From Cycle 1 Day 1 to 30 days after the date of the last study treatment administration i.e., approximately 5 years)
- Duration of response (DoR)(24 months after the Last Participant In (LPI))
- Time to response (TTR)(24 months after the Last Participant In (LPI))
- Progression free survival (PFS)(24 months after the Last Participant In (LPI))
- Minimal residual disease (MRD) status negativity(24 months after the Last Participant In (LPI))
- Change from baseline in overall side effect bother as measured by the Functional Assessment of Cancer Therapy item 5 (FACT-GP5)- Part B(From Cycle 1 Day 1 to 30 days after the date of the last study treatment administration i.e., approximately 5 years)
- Maximum observed concentration (Cmax)(Multiple timepoints from Cycle 1 Day 1 to Cycle 1 Day 8 (cycle 1=28 days))
- First time to reach Cmax (tmax)(Multiple timepoints from Cycle 1 Day 1 to Cycle 1 Day 8 (cycle 1=28 days))
- Area under the concentration versus time curve calculated from 0 to 168 hours (AUC0-168h)(Multiple timepoints from Cycle 1 Day 1 to Cycle 1 Day 8 (cycle 1=28 days))
- Proportion of participants with presence of anti-drug antibody (ADA) against SAR446523.(From Cycle 1 Day 1 to 90 days after the date of the last study treatment administration i.e., approximately 5 years)