AN OPEN-LABEL, 2-ARM, MULTICENTER, RANDOMIZED PHASE 3 STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ELRANATAMAB (PF-06863135) + DARATUMUMAB + LENALIDOMIDE VERSUS DARATUMUMAB + BORTEZOMIB + LENALIDOMIDE + DEXAMETHASONE IN TRANSPLANT-INELIGIBLE PARTICIPANTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- Pfizer
- 入组人数
- 1,116
- 试验地点
- 203
- 主要终点
- Part 1 Dose Limiting Toxicity
研究概览
简要总结
Elranatamab is a bispecific antibody: binding of elranatamab to CD3-expressing T-cells and BCMA-expressing multiple myeloma cells causes targeted T-cell-mediated cytotoxicity. The main purpose of the study is to evaluate if the combination of Elranatamab, Daratumumab and Lenalidomide offers superior clinical benefit compared with the combination of Daratumumab, Bortezomib, Lenalidomide and Dexamethasone in people with newly diagnosed multiple myeloma.
There are 2 parts to this study. Part 1 will characterize the safety and tolerability of elranatamab in combination with daratumumab and lenalidomide or in combination with lenalidomide and will identify the optimal dose(s) of the combination regimen. Part 2 of the study will evaluate the rate of minimal residual disease (MRD) negative CR and the progression free survival (PFS) of the combination of elranatamab, daratumumab, and lenalidomide compared with the combination of daratumumab, bortezomib, lenalidomide, and dexamethasone in participants with newly diagnosed multiple myeloma.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Diagnosis of multiple myeloma (MM) as defined by IMWG criteria (Rajkumar et al., 2014)
- •Measurable disease based on IMWG criteria as defined by at least 1 of the following:
- •Serum M-protein ≥0.5 g/dL (Part 1) and ≥1 g/dL (Part 2);
- •Urinary M-protein excretion ≥200 mg/24 hours;
- •Involved FLC ≥10 mg/dL (≥100 mg/L) AND abnormal serum immunoglobulin kappa to lambda FLC ratio (<0.26 or >1.65).
- •Part 1: Participants with relapsed/refractory multiple myeloma (RRMM) who have received 1-2 prior lines of therapy including at least one immunomodulatory drug and one proteasome inhibitor: or participants with newly-diagnosed multiple myeloma (NDMM) that are transplant-ineligible as defined by age ≥65 years or transplant-ineligible as defined by age <65 years with comorbidities impacting the possibility of transplant.
- •Part 2: participants with newly-diagnosed multiple myeloma that are transplant-ineligible defined as:
- •Participants not considered candidates for high-dose chemotherapy and ASCT due to age or
- •Participants with important comorbidities likely to have a negative impact on tolerability of high dose chemotherapy and ASCT.
- •ECOG performance status ≤
- •Not pregnant and willing to use contraception
- •For participants with RRMM: Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1.
排除标准
- •Smoldering Multiple Myeloma.
- •Monoclonal gammopathy of undetermined significance.
- •Waldenströms Macroglobulinemia
- •Plasma cell leukemia.
- •Active, uncontrolled bacterial, fungal, or viral infection, including (but not limited to) COVID-19/SARS-CoV-2, HBV, HCV, and known HIV or AIDS-related illness.
- •Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, carcinoma in situ, or Stage 0/1 with minimal risk of recurrence per investigator.
- •For participants with RRMM: Previous treatment with a BCMA-directed therapy or anti-CD38-directed therapy within 6 months preceding the first dose of study intervention in this study. Stem cell transplant ≤3 months prior to first dose of study intervention or active GVHD.
- •For participants with NDMM: Previous systemic treatment for MM except for a short course of corticosteroids (ie, total of 160 mg dexamethasone or equivalent before the first dose of study intervention). A cumulative dose of systemic corticosteroids equivalent to ≥20 mg of dexamethasone during screening.
- •Live attenuated vaccine administered within 4 weeks of the first dose of study intervention.
- •Administration of investigational product (eg, drug or vaccine) concurrent with study intervention or within 30 days (or as determined by the local requirement) preceding the first dose of study intervention used in this study.
研究组 & 干预措施
Part 1, Multiple Dose Levels, Elranatamab + Daratumumab + Lenalidomide
干预措施: Daratumumab (Drug)
Part 1, Dose Level 1: Elranatamab + Daratumumab + Lenalidomide
干预措施: Elranatamab (Drug)
Part 1, Dose Level 1: Elranatamab + Daratumumab + Lenalidomide
干预措施: Lenalidomide (Drug)
Part 1: Elranatamab + Lenalidomide
干预措施: Lenalidomide (Drug)
Part 2 Randomized Arm B: Daratumumab + Bortezomib + Lenalidomide + Dexamethasone
干预措施: Bortezomib (Drug)
Part 2 Randomized Arm B: Daratumumab + Bortezomib + Lenalidomide + Dexamethasone
干预措施: Lenalidomide (Drug)
Part 2 Randomized Arm B: Daratumumab + Bortezomib + Lenalidomide + Dexamethasone
干预措施: Dexamethasone (Drug)
Part 2 Randomized Arm A: Elranatamab + Daratumumab + Lenalidomide
干预措施: Elranatamab (Drug)
Part 1, Multiple Dose Levels, Elranatamab + Daratumumab + Lenalidomide
干预措施: Elranatamab (Drug)
Part 1, Dose Level 1: Elranatamab + Daratumumab + Lenalidomide
干预措施: Daratumumab (Drug)
Part 2 Randomized Arm A: Elranatamab + Daratumumab + Lenalidomide
干预措施: Daratumumab (Drug)
Part 2 Randomized Arm A: Elranatamab + Daratumumab + Lenalidomide
干预措施: Lenalidomide (Drug)
Part 1: Elranatamab + Lenalidomide
干预措施: Elranatamab (Drug)
Part 2 Randomized Arm B: Daratumumab + Bortezomib + Lenalidomide + Dexamethasone
干预措施: Daratumumab (Drug)
Part 1, Multiple Dose Levels, Elranatamab + Daratumumab + Lenalidomide
干预措施: Lenalidomide (Drug)
结局指标
主要结局
Part 1 Dose Limiting Toxicity
时间窗: From the first dose of elranatamab/first full dose in combination with EDR until 28 days (+/- visit window) from the first administration of elranatamab with daratumumab and lenalidomide
Part 2: Minimal Residual Disease negative CR rate
时间窗: At 12 months after randomization
Part 1 Dose Limiting Toxicity
时间窗: From the first dose of elranatamab/first full dose in combination with EDR until 28 days (+/- visit window) from the first administration of elranatamab with daratumumab and lenalidomide
Part 2: Progression free survival per IMWG
时间窗: From randomization up to 97 months.
Part 2: Minimal Residual Disease negativity rate
时间窗: At 12 months after randomization
次要结局
- Overall minimal residual disease negative CR rate(From date of randomization up to 97 months)
- Sustained MRD negative CR rate (Part 2)(From date of randomization up to 97 months)
- Duration of minimal residual disease negative CR (Part 2)(From date of minimal residual disease negative CR status up to 97 months)
- Health-related quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Myeloma 20 (Part 2)(From date the informed consent is signed up to 97 months)
- Overall Survival(From date of randomization up to 97 months)
- Overall minimal residual disease negativity rate(From date of randomization up to 97 months)
- Sustained MRD negativity rate (Part 2)(From date of randomization up to 97 months)
- Duration of minimal residual disease negativity (Part 2)(From date of minimal residual disease negative status up to 97 months)
- PFS by investigator(From date of randomization up to 97 months)
- PFS2 by investigator (Part 2)(From the date of randomization up to 97 months)
- Objective Response Rate(From the date of randomization up to 97 months)
- Complete Response Rate(From the date of randomization up to 97 months)
- Time to Response(From the date of randomization to date of confirmed objective response up to 97 months)
- Duration of Response(From the date of confirmed objective response up to 97 months)
- Duration of Complete Response(From the date of confirmed complete response up to 97 months)
- Frequency of treatment-emergent adverse events(From the date of first dose of study intervention up to 97 months)
- Frequency of abnormal laboratory results(From the date of first dose of study intervention up to 97 months)
- Pharmacokinetics of elranatamab when used in the elranatamab + daratumumab + lenalidomide or elranatamab + lenalidomide combinations(From date of first dose of study intervention up to 97 months)
- Incidence of Anti-Drug Antibody against elranatamab(From date of first dose of study intervention up to 97 months)
- Pharmacokinetics of daratumumab and lenalidomide when used in the elranatamab+daratumumab+lenalidomide or elranatamab+lenalidomide combinations (Part 1)(From date of first dose of study intervention up to 97 months)
- Health-related quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (Part 2)(From date the informed consent is signed up to 97 months)
- Health-related quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire -Myeloma 20 (Part 2)(From date the informed consent is signed up to 97 months)