64407564MMY1001: 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
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 279
- 试验地点
- 22
- 主要终点
- Part 1 and Part 2: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
研究概览
简要总结
The purpose of this study is to characterize the safety of Talquetamab and to determine the recommended Phase 2 dose(s) (RP2Ds) and dosing schedule assessed to be safe for Talquetamab (Part 1 [Dose Escalation]) and to further characterize the safety of Talquetamab at the recommended Phase 2 dose(s) (RP2Ds) (Part 2 [Dose Expansion]).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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 1: Participants with measurable multiple myeloma who have progressed on, or could not tolerate, all available established therapies. Part 2: Participants with multiple myeloma measurable by central laboratory assessment who have progressed on, or could not tolerate, all available established therapies; Serum monoclonal paraprotein (M-protein) level greater than or equal to (>=) 1.0 gram per deciliter (g/dL) or urine M-protein level >=200 milligram per 24 hours (mg/24 h) or light chain multiple myeloma without measurable disease in the serum or the urine: serum immunoglobulin free light chain (FLC) >= 10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio; If central laboratory assessments are not available, relevant local laboratory measurements must exceed the minimum required level by at least 25%
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
- •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 [beta-hCG]) or urine
- •Sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study, and is willing to and able participate in the study. Consent is to be obtained prior to the initiation of any study-related tests or procedures that are not part of standard-of-care for the participant's disease
排除标准
- •Participants who received or plan to receive any live, attenuated vaccine within 4 weeks prior to the first dose, during treatment, or within 4 weeks of the last dose of Talquetamab. Non-live or non-replicating vaccines approved or authorized for emergency use (example, coronavirus disease [COVID]-19) by local health authorities are allowed
- •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 greater than or equal to ( >=) 140 milligram (mg) of prednisone within the 14-day period before the first dose of study drug (does not include pretreatment medication)
- •An allogenic stem cell transplant within 6 months before first dose of study drug. Participants who received an allogeneic transplant must be off all immunosuppressive medications for 6 weeks without signs of graft-versus-host disease (GVHD); and/or an autologous stem cell transplant less than or equal to (<=) 12 weeks before first dose of study drug
- •Documented history of central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma. If either is suspected, whole body magnetic resonance imaging (MRI) and lumbar cytology are required
研究组 & 干预措施
Part 1: Dose Escalation (Talquetamab) - Intravenous (IV)
Participants will receive IV infusion of Talquetamab at minimum anticipated biologic effect level (MABEL)-based starting dose until the completion of the end of treatment visit. Subsequent dose levels will be selected based on the review of all available data including, but not limited to, pharmacokinetic, pharmacodynamic, safety, and preliminary antitumor activity data. Participants receiving IV dosing can transition to SC dosing through-out the study upon sponsor consultation. 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 1: Dose Escalation (Talquetamab) - Subcutaneous (SC)
Participants will receive Talquetamab SC. The dose levels will be selected to identify safe and tolerable putative RP2D(s). 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 2: Dose Expansion (Talquetamab)
Participants will receive IV infusion or SC injection of Talquetamab at each putative recommended Phase 2 dose(s) (RP2D[s]) as determined in Part 1. Participants receiving IV dosing can transition to SC dosing through-out the study upon sponsor consultation. 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
Part 1 and Part 2: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
时间窗: From signing of Informed Consent Form (ICF) up to follow up (until 100 days after the last dose of study drug or until the start of subsequent anticancer therapy, if earlier [approximately 2.10 years])
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
Part 1: Dose-limiting Toxicity (DLT)
时间窗: Up to Day 28
The Dose Limiting Toxicities (DLTs) are based on drug related adverse events and defined as any of the following events: hematological / non-hematological toxicity of Grade 3 or higher.
次要结局
- Part 1 and Part 2: Biomarker Assessment(Up to Cycle 7 Day 1 (each cycle of 21-days))
- Part 1: Number of Participants with Talquetamab Antibodies(Up to 4 weeks)
- Part 2: Time to Response (TTR)(From the date of first dose of study drug to the date of initial documentation of a response (approximately 2.10 years))
- Part 1: Talquetamab Serum Concentrations(Up to 4 weeks)
- Part 2: Progression-Free Survival (PFS)(Every 16 weeks until end of study, participant dies, withdrawn consent, or lost to follow up (up to 18 months))
- Part 2: Overall Response Rate (ORR)(Approximately 2.10 years)
- Part 2: Duration of Response (DOR)(From the date of initial documentation of a response to the date of first documented evidence of progressive disease (PD) (approximately 2.10 years))
- Part 2: Clinical Benefit Rate (CBR)(Approximately 2.10 years)