A Phase 1/2, First-in-Human, Open-Label, Dose Escalation Study of Talquetamab, a Humanized GPRC5D x CD3 Bispecific Antibody, in Subjects With Relapsed or Refractory Multiple Myeloma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 510
- 试验地点
- 79
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of talquetamab in participants with relapsed or refractory multiple myeloma at the recommended Phase 2 dose(s) (RP2Ds) (Part 3).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Documented initial diagnosis of multiple myeloma according to international myeloma working group (IMWG) diagnostic criteria
- •Part 3: Measurable disease cohort A, cohort B, cohort C and cohort D: multiple myeloma must be measurable by central laboratory assessment; Cohort E: Multiple myeloma must be measurable by local laboratory assessment
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2
- •Women of childbearing potential must have a negative pregnancy test at screening and prior to the first dose of study drug using a highly sensitive pregnancy test either serum (beta human chorionic gonadotropin [hCG]) or urine
- •Willing and able to adhere to the prohibitions and restrictions specified in this protocol
排除标准
- •Part 3 only: Cohort A and Cohort C only: exposed to a CAR-T or T cell redirection therapy at any time. Cohort B, Cohort D and Cohort E: T cell redirection therapy within 3 months
- •Toxicities from previous anticancer therapies should have resolved to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy
- •Received a cumulative dose of corticosteroids equivalent to >= 140 milligram (mg) of prednisone within the 14-day period before the first dose of study drug (does not include pretreatment medication)
- •Stroke or seizure within 6 months prior to signing the informed consent form (ICF)
研究组 & 干预措施
Part 3: Cohort C (Talquetamab)
Cohort C will enroll participants with multiple myeloma who have previously received >= 3 prior lines of therapy and have not been exposed to T cell redirection therapies. Participants will receive talquetamab SC biweekly at a RP2D selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study. All participants (ongoing and those who are in follow-up) will transition to OLE phase and will continue to receive the study treatment. Upon approval of amendment 19 and notification from the sponsor, participants will transition to the LTE and will continue to receive study treatment.
干预措施: Talquetamab (Drug)
Part 3: Cohort D (Talquetamab)
Cohort D will enroll participants with multiple myeloma who have previously received >= 3 prior lines of therapy. Participants will receive talquetamab SC biweekly at a RP2D selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study. Participants in this cohort will receive tocilizumab prophylaxis for cytokine release syndrome (CRS) including all outpatient dosing. Participants will transition to OLE upon communication by the sponsor. Upon approval of amendment 19 and notification from the sponsor, participants will transition to the LTE and will continue to receive study treatment.
干预措施: Talquetamab (Drug)
Part 3: Cohort E (Talquetamab)
Cohort E will enroll participants with multiple myeloma who have previously received at least 1 proteasome inhibitor (PI), 1 immunomodulatory imide drug (IMiD), and 1 anti-cluster of differentiation 38 (CD38) monoclonal antibody.
Participants will receive talquetamab SC biweekly at a RP2D selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study. Participants will receive tocilizumab prophylaxis for CRS with consolidated priming dose schedules as well as possible transition to outpatient priming dosing transition to OLE upon communication by the sponsor. Upon approval of amendment 19 and notification from the sponsor, participants will transition to the LTE and will continue to receive study treatment.
干预措施: Talquetamab (Drug)
Part 3: Cohort A (Talquetamab)
Cohort A will enroll participants with multiple myeloma who have previously received greater than or equal to (>=) 3 prior lines of therapy and have not been exposed to T cell redirection therapies. Participants will receive talquetamab subcutaneously (SC) at a recommended Phase 2 dose (RP2D) selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study. All participants (ongoing and those who are in follow-up) will transition to open-label extension (OLE) phase and will continue to receive the study treatment. Upon approval of amendment 19 and notification from the sponsor, participants will transition to the long-term extension (LTE) and will continue to receive study treatment.
干预措施: Talquetamab (Drug)
Part 3: Cohort B (Talquetamab)
Cohort B will enroll participants with multiple myeloma who have previously received >= 3 prior lines of therapy and have been exposed to T cell redirection therapies. Participants will receive talquetamab subcutaneously (SC) at a recommended Phase 2 dose (RP2D) selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study. All participants (ongoing and those who are in follow-up) will transition to OLE phase and will continue to receive the study treatment. Upon approval of amendment 19 and notification from the sponsor, participants will transition to the LTE and will continue to receive study treatment.
干预措施: Talquetamab (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: Up to 2 years and 10 months
ORR is defined as the proportion of participants who have a partial response (PR) or better according to the international myeloma working group (IMWG) criteria.
次要结局
- Number of Participants with AEs by Severity(Up to 2 years and 10 months)
- Overall Response Rate (ORR) in Participants with High-risk Molecular Features(Up to 2 years and 10 months)
- Change from Baseline in HRQoL as Assessed by EuroQol Five Dimension Five Level Questionnaire (EQ-5D-5L)(Baseline up to 2 years and 10 months)
- Duration of Response (DOR)(Up to 2 years and 10 months)
- Complete Response (CR) or Better Rate(Up to 2 years and 10 months)
- Progression-Free Survival (PFS)(Up to 2 years and 10 months)
- Number of Participants with Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability(Up to 2 years and 10 months)
- Number of Participants with Abnormalities in Clinical Laboratory Values(Up to 2 years and 10 months)
- Minimal Residual Disease (MRD) Negative Rate(Up to 2 years and 10 months)
- Stringent Complete Response (sCR) Rate(Up to 2 years and 10 months)
- Time to Response (TTR)(Up to 2 years and 10 months)
- Overall Survival (OS)(Up to 2 years and 10 months)
- Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability(Up to 2 years and 10 months)
- Number of Participants with Talquetamab Antibodies(Up to 2 years and 10 months)
- Change from Baseline in Health-Related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 item (EORTC QLQ-C30)(Baseline up to 2 years and 10 months)
- Very Good Partial Response (VGPR) or Better Rate(Up to 2 years and 10 months)
- Serum Concentration of Talquetamab(Up to 2 years and 10 months)
- Change from Baseline in HRQoL as Assessed by Patient Global Impression of Severity (PGIS)(Baseline up to 2 years and 10 months)