A PHASE 1B, OPEN-LABEL STUDY OF ELRANATAMAB IN COMBINATION WITH CARFILZOMIB PLUS DEXAMETHASONE AND ELRANATAMAB IN COMBINATION WITH PF-07901801 IN PARTICIPANTS WITH RELAPSED REFRACTORY MULTIPLE MYELOMA
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Pfizer
- 入组人数
- 59
- 试验地点
- 70
- 主要终点
- Part 1 Number of participants with dose limiting toxicity (DLT)
研究概览
简要总结
The main purpose of the study is to evaluate the safety and tolerability of the combination of elranatamab and carfilzomib and dexamethasone or elranatamab and maplirpacept.
There are 2 parts to this study. Part 1 will evaluate the safety and tolerability of elranatamab when given in combination with carfilzomib plus dexamethasone. Part 2 has 2 arms. The first will evaluate the safety and tolerability of elranatamab when given in combination with maplirpacept. The second will identify the optimal dose(s) of elranatamab plus maplirpacept.
All study medicines are given over 4-week cycles. Everyone taking part in this study will receive elranatamab as a shot under the skin. Participants in Part 1 will also receive weekly carfilzomib as an IV infusion (given directly into a vein) and dexamethasone either by mouth (as a pill) or by IV infusion. Participants in Part 2 will receive elranatamab in combination with maplirpacept as an IV infusion (given directly into a vein)
The investigators will examine the experiences of people receiving the study medicines. This will help determine if the study medicines are safe and can be used for multiple myeloma treatment. Participants will take part in this study for about 2 years after the first dose.
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
- •Prior diagnosis of multiple myeloma as defined by IMWG criteria.
- •Measurable disease based on IMWG criteria as defined by at least 1 of the following:
- •Serum M-protein ≥0.5 g/dL.
- •Urinary M-protein excretion ≥200 mg/24 hours.
- •Serum immunoglobulin FLC ≥10 mg/dL (≥100 mg/L) AND abnormal serum immunoglobulin kappa to lambda FLC ratio (<0.26 or >1.65).
- •Part 1: Received at least 1 but not more than 3 prior lines of therapy for multiple myeloma (induction therapy followed by stem cell transplant and consolidation/maintenance therapy will be considered as 1 line of therapy).
- •Part 2: Received at least 3 prior lines of therapy for multiple myeloma who are refractory to at least one IMiD, one PI and one anti-CD38 antibody.
- •ECOG performance status 0-
- •Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤
- •Not pregnant or breastfeeding and willing to use contraception.
排除标准
- •Plasma cell leukemia, Smouldering MM, Waldenströms macroglobulinemia, Amyloidosis, POEMS Syndrome, Primary refractory MM
- •Impaired cardiovascular function or clinically significant cardiovascular diseases.
- •Participants with any active, uncontrolled bacterial, fungal, or viral infection.
- •Stem cell transplant within 12 weeks prior to enrollment, or active graft versus host disease.
- •Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ.
- •Part 1: Previous treatment with a BCMA-directed therapy.
- •Part 2: Previous treatment with any anti-BCMA directed therapy, with the exception of CAR-T. Previous treatment with a CD47-SIRP alpha-directed therapy.
- •Part 1: Prior treatment with carfilzomib
- •Live attenuated vaccine within 4 weeks of the first dose of study intervention.
- •Administration with an investigational product (e.g. drug or vaccine) concurrent with study intervention or within 30 days preceding the first dose of study intervention used in this study.
- •Any of the following within 3 months of enrollment: erosive esophagitis, treatment resistant peptic ulcer, infectious or inflammatory bowel disease, pulmonary embolism or uncontrolled thromboembolic event.
- •Intolerance to or participants who have had a severe (Grade ≥3) allergic or anaphylactic reaction to antibodies or therapeutic proteins
研究组 & 干预措施
Part 1 Dose Escalation
Non randomized Elranatamab plus Carfilzomib and Dexamethasone
干预措施: Carfilzomib (Drug)
Part 1 Dose Escalation
Non randomized Elranatamab plus Carfilzomib and Dexamethasone
干预措施: Elranatamab (Drug)
Part 2B Dose Randomization
Randomized dose level Elranatamab plus Maplirpacept
干预措施: Maplirpacept (Drug)
Part 2A Dose Escalation
Non randomized Elranatamab plus Maplirpacept
干预措施: Maplirpacept (Drug)
Part 2A Dose Escalation
Non randomized Elranatamab plus Maplirpacept
干预措施: Elranatamab (Drug)
Part 2B Dose Randomization
Randomized dose level Elranatamab plus Maplirpacept
干预措施: Elranatamab (Drug)
结局指标
主要结局
Part 1 Number of participants with dose limiting toxicity (DLT)
时间窗: From first dose of elranatamab through the end of the first cycle of combination treatment, about 42 days.
Dose limiting toxicity rate based on dose limiting toxicity evaluable participants.
Part 2A Number of participants with dose limiting toxicity
时间窗: From the first dose of maplirpacept through the first cycle of combination treatment, about 64 days.
Dose limiting toxicity based on dose limiting toxicity evaluable participants.
Part 2B Number of participants with dose limiting Toxicity
时间窗: From first dose of elranatamab through the first cycle of combination treatment, about 42 days.
Dose limiting toxicity rate based on dose limiting toxicity evaluable participants.
次要结局
- Part 1: Time of Overall Survival (OS)(Assessed for approximately 2 years)
- Part 1: Percentage of Participants with an Objective Response Rate (ORR)(Assessed from enrollment for approximately 2 years.)
- Part 1: Minimal Residual Disease (MRD) Negativity Rate(Assessed for approximately 2 years)
- Part 1: Number of Participants with Treatment Emergent Adverse Events (TEAE) by Seriousness and Relationship to Treatment(Assessed from baseline up to 90 days after last dose of study treatment.)
- Part 1: Number of Participants with Adverse Events (AE) characterized by type, frequency, severity.(Assessed from baseline up to 90 days after last dose of study treatment.)
- Part 1: Percent of participants with Best Overall Response (BOR)(Assessed for approximately 2 years)
- Part 1: Percentage of participants with a complete response rate (CRR)(Assessed for approximately 2 years)
- Part 1: Concentrations of elranatamab(Assessed for approximately 2 years.)
- Part 1: Percentage of participants with positive anti-drug antibodies (ADA) against elranatamab(Assessed for approximately 2 years.)
- Part 1: Number of Participants with Clinically Significant Change From Baseline in Laboratory Abnormalities(Accessed from baseline up to 90 days after the last dose of study treatment.)
- Part 1: Time to Response (TTR)(Assessed for approximately 2 years.)
- Part 1: Duration of Response (DOR)(Assessed for approximately 2 years.)
- Part 1: Duration of Complete Response (DOCR)(Assessed for approximately 2 years.)
- Part 1: Time of Progression Free Survival (PFS)(Assessed from enrollment until Progressive Disease or death for approximately 2 years.)
- Part 1: Concentrations of carfilzomib(Once approximately 7 weeks from enrollment.)
- Part 2A: Number of Participants with Treatment Emergent Adverse Events (TEAE) by Seriousness and Relationship to Treatment(Assessed from baseline up to 90 days after last dose of study treatment.)
- Part 2A: Number of Participants with Adverse Events (AE) characterized by type, frequency, severity.(Assessed from baseline up to 90 days after last dose of study treatment.)
- Part 2A: Number of Participants with Clinically Significant Change From Baseline in Laboratory Abnormalities(Accessed from baseline up to 90 days after the last dose of study treatment.)
- Part 2A: Percent of participants with Best Overall Response (BOR)(Assessed for approximately 2 years)
- Part 2A: Percentage of Participants with an Objective Response Rate (ORR)(Assessed from enrollment for approximately 2 years.)
- Part 2A: Percentage of participants with a complete response rate (CRR)(Assessed for approximately 2 years)
- Part 2A: Time to Response (TTR)(Assessed for approximately 2 years.)
- Part 2A: Duration of Response (DOR)(Assessed for approximately 2 years.)
- Part 2A: Duration of Complete Response (DOCR)(Assessed for approximately 2 years.)
- Part 2A: Time of Progression Free Survival (PFS)(Assessed from enrollment until Progressive Disease or death for approximately 2 years.)
- Part 2A: Time of Overall Survival (OS)(Assessed for approximately 2 years)
- Part 2A: Minimal Residual Disease (MRD) Negativity Rate(Assessed for approximately 2 years)
- Part 2A: Concentrations of maplirpacept(Assessed for approximately 2 years.)
- Part 2A: Concentrations of elranatamab(Assessed for approximately 2 years.)
- Part 2A: Percentage of participants with positive anti-drug antibodies (ADA) against elranatamab(Assessed for approximately 2 years.)
- Part 2A: Percentage of participants with positive anti-drug antibodies (ADA) against maplirpacept(Assessed for approximately 2 years.)
- Part 2B: Percentage of participants with a complete response rate (CRR)(Assessed for approximately 2 years)
- Part 2B: Number of Participants with Treatment Emergent Adverse Events (TEAE) by Seriousness and Relationship to Treatment(Assessed from baseline up to 90 days after last dose of study treatment.)
- Part 2B: Number of Participants with Adverse Events (AE) characterized by type, frequency, severity.(Assessed from baseline up to 90 days after last dose of study treatment.)
- Part 2B: Number of Participants with Clinically Significant Change From Baseline in Laboratory Abnormalities(Accessed from baseline up to 90 days after the last dose of study treatment.)
- Part 2B: Percent of participants with Best Overall Response (BOR)(Assessed for approximately 2 years)
- Part 2B: Percentage of Participants with an Objective Response Rate (ORR)(Assessed from enrollment for approximately 2 years.)
- Part 2B: Time to Response (TTR)(Assessed for approximately 2 years.)
- Part 2B: Duration of Response (DOR)(Assessed for approximately 2 years.)
- Part 2B: Duration of Complete Response (DOCR)(Assessed for approximately 2 years.)
- Part 2B: Time of Progression Free Survival (PFS)(Assessed from enrollment until Progressive Disease or death for approximately 2 years.)
- Part 2B: Time of Overall Survival (OS)(Assessed for approximately 2 years)
- Part 2B: Minimal Residual Disease (MRD) Negativity Rate(Assessed for approximately 2 years)
- Part 2B: Concentrations of maplirpacept(Assessed for approximately 2 years.)
- Part 2B: Concentrations of elranatamab(Assessed for approximately 2 years.)
- Part 2B: Percentage of participants with positive anti-drug antibodies (ADA) against elranatamab(Assessed for approximately 2 years.)
- Part 2B: Percentage of participants with positive anti-drug antibodies (ADA) against maplirpacept(Assessed for approximately 2 years.)