A PHASE 1B/2, OPEN-LABEL STUDY TO EVALUATE THE SAFETY, PHARMACOKINETICS, PHARMACODYNAMICS, AND EFFICACY OF ELRANATAMAB (PF-06863135) IN CHINESE PARTICIPANTS WITH MULTIPLE MYELOMA WHO ARE REFRACTORY TO AT LEAST ONE PROTEASOME INHIBITOR, ONE IMMUNOMODULATORY DRUG AND ONE ANTI-CD38 ANTIBODY (TRIPLE-CLASS REFRACTORY MM)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 39
- 试验地点
- 15
- 主要终点
- Phase 1b: Number of Participants With Dose-Limiting Toxicities (DLT)
研究概览
简要总结
The purpose of this study is to understand the study medicine (called Elranatamab, or PF-06863135) as potential treatment for refractory multiple myeloma. Multiple myeloma is a form of cancer in the bone that forces healthy blood cells to go out. Sometimes, multiple myeloma does not respond to current therapy or quickly progresses, and this is called refractory multiple myeloma.
Elranatamab is a study medicine that target multiple myeloma and activates the human body to fight against this disease. We are seeking Chinese participants to take part in this study. The study will be 2 parts, called part 1b and part 2. In part 1b, participants will receive Elranatamab at 2 steps priming and full dose as a sc (subcutaneous injection) therapy. We will monitor participants' safety and reactions to the study medicine. This will help us understand the dosage of Elranatamab to be used safely.
In part 2 of the study, participants will receive Elranatamab and their multiple myeloma growth will be monitored. This will help us understand if Elranatamab, when used alone, may be a therapy for refractory multiple myeloma. Participants in this part of the study are expected to take part for about 2 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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 (IMWG criteria, Rajkumar et al, 2014)
- •Measurable disease, 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
- •Refractory to at least one IMiD
- •Refractory to at least one PI
- •Refractory to at least one anti-CD38 antibody
- •Relapsed/refractory to last anti-myeloma regimen
- •ECOG performance status ≤2
- •Adequate BM function characterized by the following:
- •Absolute neutrophil count ≥1.0 × 10^9/L
- •Platelets ≥ 25 × 10^9/L
- •Hemoglobin ≥8 g/dL
- •Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1
- •Not pregnant and willing to use contraception
排除标准
- •Smoldering multiple myeloma
- •Active Plasma cell leukemia
- •Amyloidosis
- •POEMS syndrome
- •Stem cell transplant or active GVHD within 12 weeks prior to enrollment.
- •Previous treatment with an anti-BCMA directed therapy
- •Impaired cardiovascular function or clinically significant cardiovascular diseases
- •Ongoing Grade ≥2 peripheral sensory or motor neuropathy. History of GBS or GBS variants, or history of any Grade ≥3 peripheral motor polyneuropathy.
- •Active HBV, HCV, SARS-CoV2, HIV, or any active, uncontrolled bacterial, fungal, or viral infection
- •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.
- •Previous administration with an investigational drug within 30 days or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer)
研究组 & 干预措施
Elranatamab
BCMA-CD3 bispecific antibody
干预措施: Elranatamab (Drug)
结局指标
主要结局
Phase 1b: Number of Participants With Dose-Limiting Toxicities (DLT)
时间窗: Cycle 1 (28 days)
Grade(G)4 neutropenia \>5 day; febrile neutropenia (absolute neutrophil count \[ANC\] \<1000/millimeter cube (mm\^3) with single temperature \>38.3 degree Celsius (deg C) or sustained temp\>=38 deg C for \>1 hour(H); G\>=3 neutropenia with infection; G4 thrombocytopenia (unless baseline count \>=25,000/mm\^3 and \<50,000/mm\^3, in which case G4 thrombocytopenia to be accompanied by \>=G2 bleeding); Platelet count \<10,000/mm\^3; G3 thrombocytopenia with \>=G2 bleeding; G\>=4 AE; G3 cytokine release syndrome(CRS) except CRS not maximally treated/improved to \<=G1 within 48H; G3 AE except AE attributed to CRS, G3 nausea,vomiting,diarrhea improved to G\<=2 within 72H after medical management, G3 fatigue \<1 week, G3 AE recovered to baseline/G1 within 5 day; confirmed drug-induced liver injury; G3-4 laboratory (lab) abnormality except G3-4 lab abnormality improved to G\<=2 within 72H after medical management \& without sequelae;G3 injection site reaction; G2/other clinically important AE may be considered DLT.
Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) as Per International Myeloma Working Group (IMWG) Criteria
时间窗: From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (approximately up to 16 months)
ORR: Percentage of participants with best overall response of confirmed stringent complete response (sCR), CR, very good partial response (VGPR) or PR per IMWG criteria. sCR: CR \& normal serum free light chain (sFLC) ratio \& absence of clonal cells in BMB/BMA by IH, IF, or flow cytometry. CR: negative immunofixation on serum \& urine, disappearance of any soft tissue plasmacytoma \& \<5% plasma cells in BMA, if disease measurable by sFLC only, preceding criteria plus normal sFLC ratio. VGPR: Serum \& urine M-protein detectable by immunofixation but not on electrophoresis; or \>=90% reduction in serum M-protein \& urine M-protein level \<100mg/24h. PR: \>=50% reduction in serum M-protein \& reduction in 24h urinary M-protein by \>=90% or \<200 mg/24h. If serum \& urine M-protein were unmeasurable, VGPR \& PR: \>=90% \& \>=50% decrease in difference respectively between involved \& uninvolved sFLC levels \& if present at baseline, \>=90% \& \>=50% reduction in soft tissue plasmacytomas' size.
次要结局
- Duration of Response (DOR) as Per IMWG Criteria by Investigator Assessment(From first documentation of objective response subsequently confirmed until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurred first, or censoring (up to approximately 37 months))
- Complete Response Rate (CRR) as Per IMWG Criteria by BICR(From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (up to approximately 37 months))
- Complete Response Rate (CRR) as Per IMWG Criteria by Investigator Assessment(From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (up to approximately 37 months))
- Objective Response Rate (ORR) as Per IMWG Criteria by Investigator Assessment(From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (up to approximately 37 months))
- Duration of Complete Response (DOCR) as Per IMWG Criteria by BICR(From first documentation of sCR/CR subsequently confirmed until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurred first, or censoring (up to approximately 37 months))
- Duration of Response (DOR) as Per IMWG Criteria by BICR(From first documentation of objective response subsequently confirmed until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurred first, or censoring (up to approximately 37 months))
- Duration of Complete Response (DOCR) as Per IMWG Criteria by Investigator Assessment(From the first documentation of sCR/CR, until confirmed PD per IMWG criteria, or death due to any cause, whichever occurred first (up to approximately 37 months))
- Progression Free Survival (PFS) as Per IMWG Criteria by BICR(From date of first dose until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurred first, or censoring (up to approximately 37 months))
- Progression Free Survival (PFS) as Per IMWG Criteria by Investigator Assessment(From date of first dose until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurred first, or censoring (up to approximately 37 months))
- Overall Survival (OS)(From the date of first dose until death due to any cause. Participants not known to have died were censored on the date of last known alive (up to approximately 37 months))
- Time-to-Response (TTR) as Per IMWG Criteria by BICR(From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurs first (approximately up to 16 months))
- Time-to-Response (TTR) as Per IMWG Criteria by Investigator Assessment(From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurs first (up to approximately 37 months))
- Minimal Residual Disease (MRD) Negativity Rate Per IMWG Sequencing Criteria(From date of first dose until confirmed disease progression, death, start of new anticancer therapy, whichever occurred first (up to approximately 37 months))
- Number of Participants With Treatment Emergent Adverse Events (TEAE), Serious TEAEs, Treatment Related TEAEs, Serious Treatment Related TEAEs as Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0(From the date of first dose up to 90 days after last dose or new anticancer therapy whichever occurred first (up to approximately 37 months))
- Number of Participants With Cytokine Release Syndrome (CRS) Graded According to American Society for Transplantation and Cellular Therapy (ASTCT) Criteria(From the date of first dose up to 90 days after last dose or new anticancer therapy whichever occurred first (up to approximately 37 months))
- Number of Participants With Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) Graded According to ASTCT Criteria(From the date of first dose up to 90 days after last dose or new anticancer therapy whichever occurred first (up to approximately 37 months))
- Maximum Serum Concentration (Cmax) of Free Elranatamab(Cycle 1: Pre-dose, 6 hours post-dose on Day 1, 24, 48 hours post-dose, Day 4: pre-dose, 24 hour post-dose, Day 8 pre-dose, 6 hours post-dose, Day 15,22: pre-dose, Cycles 2, 3 ,4,7: pre-dose (1 cycle =28 days))
- Time To Maximum Serum Concentration (Tmax) of Free Elranatamab(Cycle 1: Pre-dose, 6 hours post-dose on Day 1, 24, 48 hours post-dose, Day 4: pre-dose, 24 hour post-dose, Day 8 pre-dose, 6 hours post-dose, Day 15,22: pre-dose, Cycles 2, 3 ,4,7: pre-dose (1 cycle =28 days))
- Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) of Free Elranatamab(Cycle 1: Pre-dose, 6 hours post-dose on Day 1, 24, 48 hours post-dose, Day 4: pre-dose, 24 hour post-dose, Day 8 pre-dose, 6 hours post-dose, Day 15,22: pre-dose, Cycles 2, 3 ,4,7: pre-dose (1 cycle =28 days))
- Serum Concentration of Free Elranatamab(Up to 37 months)
- Percentage of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) Against Elranatamab(From the date of first dose up to 37 months)
- Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life of Cancer Participants Core Module (EORTC QLQ-C30)(Baseline and up to 37 months)
- Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Myeloma-Specific Module (EORTC QLQ-MY20)(Baseline and up to 37 months)
- Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Chemotherapy-Induced Peripheral Neuropathy (EORTC QLQ CIPN20)(Baseline and up to 37 months)
- Change From Baseline in EuroQol Five Dimensions Questionnaire (EQ-5D) Index Score and in EQ-5D Visual Analogue Score (VAS) (EQ-VAS)(Baseline and up to 37 months)