An Open-Label, Multicenter, Phase Ib Trial Evaluating the Safety, Pharmacokinetics, and Activity of the Combination of Cevostamab and Elranatamab in Patients With Relapsed or Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 20
- 主要终点
- Number of Participants With Adverse Events (AEs)
研究概览
简要总结
The purpose of the study is to evaluate safety and tolerability of the combination of cevostamab plus elranatamab and also determine the recommended Phase II regimen (RP2R) for the study treatment. The study consists of a safety lead-in stage, and an expansion stage.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- •Diagnosis of R/R MM per IMWG criteria
- •For female participants of childbearing potential: agreement to remain abstinent or use contraception
- •For male participants: agreement to remain abstinent or use a condom
排除标准
- •Prior treatment with cevostamab or another agent targeting fragment crystallizable receptor-like 5 (FcRH5)
- •Prior treatment with elranatamab
- •Prior allogeneic stem cell transplantation (SCT)
- •Absolute plasma cell count exceeding 500 per milliliter (mL) or 5% of the peripheral blood white cells
- •Diagnosis of Waldenström macroglobulinemia or polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes (POEMS) syndrome
- •Participants with known history of amyloidosis
- •History of autoimmune disease
- •History of confirmed progressive multifocal leukoencephalopathy
- •Peripheral motor polyneuropathy of prespecified grade
- •Known or suspected chronic cytomegalovirus (CMV) and/or Epstein-Barr virus (EBV) infection
- •Known history of hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS)
- •Acute or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
- •Human immunodeficiency virus (HIV) seropositivity
- •History of central nervous system (CNS) myeloma disease
- •Significant cardiovascular disease
研究组 & 干预措施
Dose Expansion Cohort (Monotherapy)
Participants will receive elranatamab SC, with step-up dosing in pre-phase following which they will receive elranatamab, at the assigned dose as a SC injection until disease progression or unacceptable toxicity.
干预措施: Elranatamab (Drug)
Dose Expansion Cohort (Combined Therapy)
Participants will receive cevostamab, IV, in combination with elranatamab, SC, with step-up dosing in pre-phase following which they will receive elranatamab, at the assigned dose as a SC injection until disease progression or unacceptable toxicity. Participants will also receive cevostamab at the assigned dose as IV infusion until disease progression or unacceptable toxicity or up to 1 year on treatment, whichever occurs first.
干预措施: Tocilizumab (Drug)
Safety Lead-In Cohort
Participants will receive cevostamab, intravenously (IV), in combination with elranatamab, subcutaneously (SC), with step-up dosing of each drug in pre-phase following which they will receive elranatamab, at the assigned dose as a SC injection until disease progression or unacceptable toxicity. Participants will also receive cevostamab at the assigned dose as IV infusion until disease progression or unacceptable toxicity or up to 1 year on treatment, whichever occurs first.
干预措施: Tocilizumab (Drug)
Dose Expansion Cohort (Combined Therapy)
Participants will receive cevostamab, IV, in combination with elranatamab, SC, with step-up dosing in pre-phase following which they will receive elranatamab, at the assigned dose as a SC injection until disease progression or unacceptable toxicity. Participants will also receive cevostamab at the assigned dose as IV infusion until disease progression or unacceptable toxicity or up to 1 year on treatment, whichever occurs first.
干预措施: Cevostamab (Drug)
Safety Lead-In Cohort
Participants will receive cevostamab, intravenously (IV), in combination with elranatamab, subcutaneously (SC), with step-up dosing of each drug in pre-phase following which they will receive elranatamab, at the assigned dose as a SC injection until disease progression or unacceptable toxicity. Participants will also receive cevostamab at the assigned dose as IV infusion until disease progression or unacceptable toxicity or up to 1 year on treatment, whichever occurs first.
干预措施: Elranatamab (Drug)
Safety Lead-In Cohort
Participants will receive cevostamab, intravenously (IV), in combination with elranatamab, subcutaneously (SC), with step-up dosing of each drug in pre-phase following which they will receive elranatamab, at the assigned dose as a SC injection until disease progression or unacceptable toxicity. Participants will also receive cevostamab at the assigned dose as IV infusion until disease progression or unacceptable toxicity or up to 1 year on treatment, whichever occurs first.
干预措施: Cevostamab (Drug)
Dose Expansion Cohort (Combined Therapy)
Participants will receive cevostamab, IV, in combination with elranatamab, SC, with step-up dosing in pre-phase following which they will receive elranatamab, at the assigned dose as a SC injection until disease progression or unacceptable toxicity. Participants will also receive cevostamab at the assigned dose as IV infusion until disease progression or unacceptable toxicity or up to 1 year on treatment, whichever occurs first.
干预措施: Elranatamab (Drug)
结局指标
主要结局
Number of Participants With Adverse Events (AEs)
时间窗: From signing of informed consent up to end of study (EOS) (approximately 36 months)
Adverse events will be reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0). The severity of CRS, immune effector cell-associated neurotoxicity syndrome (ICANS) and hemophagocytic lymphohistiocytosis (HLH) will be graded based on the American Society for Transplantation and Cellular Therapy (ASTCT) Grading Scales.
Number of Participants With Adverse Events (AEs)
时间窗: From signing of informed consent up to end of study (EOS) (approximately 36 months)
Adverse events will be reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0). The severity of CRS, immune effector cell-associated neurotoxicity syndrome (ICANS) and hemophagocytic lymphohistiocytosis (HLH) will be graded based on the American Society for Transplantation and Cellular Therapy (ASTCT) Grading Scales.
Recommended Phase II Regimen (RP2R)
时间窗: Up to approximately 36 months
次要结局
- Objective Response Rate (ORR) as Determined by the Investigator per International Myeloma Working Group (IMWG) Criteria(Up to approximately 36 months)
- Time to Best Response (for Participants who Achieve a Response of PR or Better)(Up to approximately 36 months)
- Complete Response (CR)/ Stringent Complete Response (sCR) Rate as Determined by the Investigator per IMWG Criteria(Up to approximately 36 months)
- Rate of Very Good Partial Response (VGPR) or Better, as Determined by the Investigator per IMWG Criteria(Up to approximately 36 months)
- Duration of Response (DOR) as Determined by the Investigator (for Participants who Achieve a Response of Partial Response (PR) or Better)(Up to approximately 36 months)
- Overall Survival (OS)(Up to approximately 36 months)
- Progression-Free Survival as Determined by the Investigator per IMWG Criteria(Up to approximately 36 months)
- Serum Concentration of Cevostamab at Specified Timepoints(Up to approximately 36 months)
- Time to First Response (for Participants who Achieve a Response of PR or Better)(Up to approximately 36 months)
- Number of Participants with Anti-Drug Antibody (ADA) Against Cevostamab(Up to approximately 36 months)
- Serum Concentration of Elranatamab at Specified Timepoints(Up to approximately 36 months)
- Number of Participants with ADA Against Elranatamab(Up to approximately 36 months)