A Phase 1b/2 Dose Escalation and Expansion Study of the Combination of the Bispecific T Cell Redirection Antibodies Talquetamab and Teclistamab in Participants 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
- 228
- 试验地点
- 69
- 主要终点
- Part 1: Number of Participants with Dose Limiting Toxicity (DLT)
研究概览
简要总结
The purpose of this study is to identify the recommended Phase 2 regimen(s) (RP2R[s]) and schedule for the study treatment (Part 1), to characterize the safety of the RP2R(s) for the study treatment (Part 2) and to evaluate the anticancer activity of talquetamab + teclistamab in participants with relapsed or refractory multiple myeloma and extramedullary disease (EMD) (Part 3).
详细描述
Multiple myeloma is a malignant plasma cell disorder characterized by production of monoclonal proteins (M proteins), which are comprised of pathologic immunoglobulins (Ig) or fragments of such, which have subsequently lost their normal function. Rationale for combining talquetamab and teclistamab is the targeting of multiple proteins on the surface of multiple myeloma cells resulting in cell lysis. This study consists of 3 periods: screening phase (up to 28 days), treatment phase (start of study drug administration and continues until the completion of the end of treatment [EOT] visit); and a post-treatment follow-up phase (after end of treatment and up to 16 weeks after last dose of study drug(s) for each participant). End of study is defined as 2 years after the last participant has received his or her initial dose of the treatment combination. Total duration of study is Approximately 5 years. Efficacy, safety, pharmacokinetics (PK), immunogenicity, and biomarkers will be assessed at specified time points during this study. Participants safety and study conduct will be monitored throughout the study.
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 and 2: Participant could not tolerate or has disease that is relapsed or refractory to established therapies, including the last line of therapy. Part 3: (a) Relapsed or refractory disease, and exposed to a PI, IMiD, and an anti-CD38 mAb; (b) Documented evidence of progressive disease based on investigator's determination of response by IMWG criteria on or after their last regimen
- •Part 1 and Part 2: Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1 at screening and immediately before the start of study drug administration. Part 3: ECOG performance status grade of 0, 1, or 2 at screening and immediately before the start of study drug administration
排除标准
- •All Parts: Targeted therapy, epigenetic therapy, or treatment with an investigational treatment or an invasive investigational medical device within 21 days or at least 5 half-lives, whichever is less. Part 3: prior BCMA targeted bispecific antibody therapy; prior GPRC5D targeted therapy
- •All Parts: Allogeneic stem cell transplant within 6 months before the first dose of study treatment.
- •All Parts: Central nervous system involvement or clinical signs of meningeal involvement of multiple myeloma.
- •All Parts: Active plasma cell leukemia (greater than [>]2.0*10^9/L plasma cells by standard differential), Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M- protein, and skin changes), or primary amyloid light chain amyloidosis
研究组 & 干预措施
Part 1: Dose Escalation
Participants will receive tec+tal in 28-day cycles following initial step-up doses. Upon sponsor notification, participants will enter the long-term extension (LTE) Phase or Drug-access Long-term Extension (DA-LTE) Phase and will continue to receive study treatment until disease progression, unacceptable toxicity, withdrawal of consent, discontinuation deemed necessary by the investigator or the sponsor, or access becomes available through another source such as but not limited to commercial availability, or a patient access program.
干预措施: Talquetamab (Drug)
Part 1: Dose Escalation
Participants will receive tec+tal in 28-day cycles following initial step-up doses. Upon sponsor notification, participants will enter the long-term extension (LTE) Phase or Drug-access Long-term Extension (DA-LTE) Phase and will continue to receive study treatment until disease progression, unacceptable toxicity, withdrawal of consent, discontinuation deemed necessary by the investigator or the sponsor, or access becomes available through another source such as but not limited to commercial availability, or a patient access program.
干预措施: Teclistamab (Drug)
Part 2: Dose Expansion
Participants will receive treatment doses (combination of tal+tec regimen) which will be determined by the recommended Phase 2 regimen (s) (RP2R[s]) of the study treatment identified in Part 1. Upon sponsor notification, participants will enter the LTE Phase or DA-LTE Phase and will continue to receive study treatment until disease progression, unacceptable toxicity, withdrawal of consent, discontinuation deemed necessary by the investigator or the sponsor, or access becomes available through another source such as but not limited to commercial availability, or a patient access program.
干预措施: Talquetamab (Drug)
Part 2: Dose Expansion
Participants will receive treatment doses (combination of tal+tec regimen) which will be determined by the recommended Phase 2 regimen (s) (RP2R[s]) of the study treatment identified in Part 1. Upon sponsor notification, participants will enter the LTE Phase or DA-LTE Phase and will continue to receive study treatment until disease progression, unacceptable toxicity, withdrawal of consent, discontinuation deemed necessary by the investigator or the sponsor, or access becomes available through another source such as but not limited to commercial availability, or a patient access program.
干预措施: Teclistamab (Drug)
Part 3: Phase 2
Participants will receive teclistamab + talquetamab combination therapy, at the RP2R selected from Part 1 and Part 2. Upon sponsor notification, participants will enter the LTE Phase or DA-LTE Phase and will continue to receive study treatment until disease progression, unacceptable toxicity, withdrawal of consent, discontinuation deemed necessary by the investigator or the sponsor, or access becomes available through another source such as but not limited to commercial availability, or a patient access program.
干预措施: Talquetamab (Drug)
Part 3: Phase 2
Participants will receive teclistamab + talquetamab combination therapy, at the RP2R selected from Part 1 and Part 2. Upon sponsor notification, participants will enter the LTE Phase or DA-LTE Phase and will continue to receive study treatment until disease progression, unacceptable toxicity, withdrawal of consent, discontinuation deemed necessary by the investigator or the sponsor, or access becomes available through another source such as but not limited to commercial availability, or a patient access program.
干预措施: Teclistamab (Drug)
结局指标
主要结局
Part 1: Number of Participants with Dose Limiting Toxicity (DLT)
时间窗: Approximately 5 years 10 months
The dose limiting toxicities are based on drug related adverse events and defined as any of the following events: hematological or non-hematological toxicity of grade 3 or higher.
Part 1: Severity of DLT as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)
时间窗: Approximately 5 years 10 months
Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening, and Grade 5= Death related to adverse event.
Part 2: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability
时间窗: Approximately 5 years 10 months
An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect, and suspects transmission of any infectious agent via a medicinal product, is medically important.
Part 2: Number of Participants with Adverse Events and SAEs by Severity
时间窗: Approximately 5 years 10 months
Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening, and Grade 5= Death related to adverse event.
Part 3: Overall Response Rate (ORR)
时间窗: Approximately 5 years 10 months
ORR is defined as the percentage of participants who have a partial response (PR) or better according Independent Review Committees (IRC).
次要结局
- Parts 1, 2 and 3: Serum Concentration of Talquetamab(Approximately 5 years 10 months)
- Parts 1, 2 and 3: Serum Concentration of Teclistamab(Approximately 5 years 10 months)
- Part 1 and Part 2: Serum Concentration of Daratumumab(Approximately 5 years 10 months)
- Parts 1, 2 and 3: Number of Participants with Anti-Drug Antibodies to Talquetamab(Approximately 5 years 10 months)
- Parts 1, 2 and 3: Number of Participants with Anti-Drug Antibodies to Teclistamab(Approximately 5 years 10 months)
- Part 1 and Part 2: Number of Participants with Anti-Drug Antibodies to Daratumumab(Approximately 5 years 10 months)
- Part 1 and Part 2: Overall Response Rate (ORR)(Approximately 5 years 10 months)
- Parts 1, 2 and 3: Very Good Partial Response (VGPR) or Better Response Rate(Approximately 5 years 10 months)
- Parts 1, 2 and 3: Complete Response (CR) or Better Response Rate(Approximately 5 years 10 months)
- Part 1, 2 and 3: Stringent Complete Response (sCR) Rate(Approximately 5 years 10 months)
- Parts 1, 2 and 3: Duration of Response (DOR)(Approximately 5 years 10 months)
- Parts 1, 2 and 3: Time to Response(Approximately 5 years 10 months)
- Part 3: Progression free Survival (PFS)(Approximately 5 years 10 months)
- Part 3: Overall Survival (OS)(Approximately 5 years 10 months)
- Part 3: Number of Participants with Adverse Events(Approximately 5 years 10 months)
- Part 3: Number of Participants with Adverse Events by Severity(Approximately 5 years 10 months)