A PHASE 1B/2, OPEN LABEL UMBRELLA STUDY OF ELRANATAMAB (PF-06863135), A B-CELL MATURATION ANTIGEN (BCMA) CD3 BISPECIFIC ANTIBODY, IN COMBINATION WITH OTHER ANTI-CANCER TREATMENTS IN PARTICIPANTS WITH MULTIPLE MYELOMA
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 46
- 试验地点
- 47
- 主要终点
- SSA: Number of Participants With Dose Limiting Toxicities (DLTs)- Phase 1b Dose Escalation
研究概览
简要总结
The purpose of this study is to determine the Recommended Phase 2 Dose and clinical benefit of elranatamab in combination with other anti-cancer therapies in participants with multiple myeloma.
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
- •Relapsed/refractory multiple myeloma with at least 3 prior lines of therapy
- •Refractory to at least one IMiD, one proteasome inhibitor, and one anti-CD38 antibody
- •Measurable disease defined by at least one of the following:
- •Serum M-protein >/= 0.5 g/dL by SPEP
- •Urinary M-protein excretion >/= 200 mg/24 hours by UPEP
- •Serum immunoglobulin FLC >/= 10 mg/dL (>/= 100 mg/L) AND abnormal serum immunoglobulin kappa to lambda FLC ratio
- •ECOG performance status 0 -1
- •Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade </= 1
排除标准
- •Active plasma cell leukemia
- •Amyloidosis
- •Stem cell transplant with 12 weeks prior to enrollment, or active GVHD
- •POEMS syndrome
- •Any active uncontrolled bacterial, fungal, or viral infection
- •Impaired cardiovascular function or clinically significant cardiovascular diseases within 6 months prior to enrollment
- •Previous administration with an investigational drug within 30 days or 5 half-lives preceding the first dose of study treatment (whichever is longer)
- •Sub-Study A Only: Previous treatment with BCMA bispecific antibody
- •Sub-Study B Only: Previous treatment with BCMA directed therapy
研究组 & 干预措施
Sub-Study A
BCMA-CD3 bispecific antibody + gamma secretase inhibitor
干预措施: Elranatamab + Nirogacestat (Drug)
Sub-Study B
BCMA-CD3 bispecific antibody + immunomodulatory drug
干预措施: Elranatamab + lenalidomide + dexamethasone (Drug)
结局指标
主要结局
SSA: Number of Participants With Dose Limiting Toxicities (DLTs)- Phase 1b Dose Escalation
时间窗: From Cycle 0 Day 1 through Cycle 1 Day 28 (approximately up to 35 days)
DLT- Hematological:Grade (G)4 neutropenia \>5 days; febrile neutropenia; G\>=3 neutropenia, infection; G4 thrombocytopenia; G3 thrombocytopenia and G\>=2 bleeding. Non-hematological: G\>=4 adverse events(AEs); G3 cytokine release syndrome(CRS) \[except CRS not been maximally treated or improved to G\<=1 in 48 hours\]; G3 AEs (except AEs attributed to CRS, G3 nausea, vomiting, diarrhea that improve to G2\<=72 hours after maximal medical management has been initiated, G3 fatigue \< 1 week); confirmed drug-induced liver injury meeting Hy's law criteria; G3-4 laboratory abnormalities(except not associated with clinical sequelae and improve to G=\<2 in 72 hours); G2 clinically important/persistent AEs(cause significant dose delay/reduction) may be DLT; G3 injection site reaction, allergic reaction, anaphylaxis. Common Terminology Criteria for Adverse Events(CTCAE) version 5.0: G1:mild AE, G2:moderate, G3:severe, G4:life-threatening consequences; urgent intervention indicated, G5:death related to AE.
SSB: Number of Participants With DLTs- Phase 1b
时间窗: From Cycle 0 Day 1 through Cycle 1 Day 28 (approximately up to 42 days)
Hematological: G4 neutropenia \>5 days; febrile neutropenia; G\>=3 neutropenia with infection; G4 thrombocytopenia; G3 thrombocytopenia with G\>=2 bleeding. Non-hematological: G\>=4 AEs; G3 CRS (except CRS events: not been maximally treated or improved to grade \<=1 within 48 hours); G3 AEs (except: AEs attributed to CRS, G3 nausea, vomiting and diarrhea that improve to G2\<=72 hours after maximal medical management has been initiated, G3 fatigue \< 1 week); confirmed drug-induced liver injury meeting Hy's law criteria; G 3-4 laboratory abnormalities (except: not associated with clinical sequelae and improve to G=\<2 within 72 hours); Other clinically important/persistent AEs (that cause significant dose delay/reduction) may be DLT; G3 injection site reaction. CTCAE version 5.0: G1: Mild AE, G2: Moderate, G3: Severe, G4: Life-threatening consequences; urgent intervention indicated, G5: Death related to AE.
次要结局
- SSA: Progression Free Survival (PFS) as Per IMWG Criteria as Determined by Investigator- Phase 1b(From treatment initiation till study completion)
- SSA: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Related TEAEs- Phase 1b(From treatment initiation till study completion)
- SSA: Number of Participants With Severity of AEs According to Cytokine Release Syndrome (CRS) Graded According to American Society for Transplantation and Cellular Therapy (ASTCT) Grading Criteria 2019- Phase 1b(From treatment initiation till study completion)
- SSA: Number of Participants With Severity of AEs According to Immune Effector Cell-associated Neurotoxicity Syndrome ICANS Graded According to ASTCT Grading Criteria 2019- Phase 1b(From treatment initiation till study completion)
- SSA: Number of Participants With Laboratory Abnormalities- Phase 1b(From treatment initiation till study completion)
- SSA: Number of Participants With Neutralizing Antibodies (NAb)- Phase 1b(From treatment initiation till study completion)
- SSA: Objective Response Rate (ORR) as Per International Myeloma Working Group (IMWG) Criteria as Determined by Investigator- Phase 1b(From treatment initiation till study completion)
- SSA: Complete Response Rate (CRR) as Per IMWG Criteria as Determined by Investigator- Phase 1b(From treatment initiation till study completion)
- SSA: Time to Response (TTR) as Per IMWG Criteria as Determined by Investigator-Phase 1b(From treatment initiation till study completion)
- SSA: Duration of Response (DOR) as Per IMWG Criteria as Determined by Investigator- Phase 1b(From treatment initiation till study completion)
- SSA: Duration of Complete Response (DOCR) as Per IMWG Criteria as Determined by Investigator- Phase 1b(From treatment initiation till study completion)
- SSA: Overall Survival (OS)- Phase 1b(From treatment initiation till study completion)
- SSA: Minimal Residual Disease (MRD) Negativity Rate as Per IMWG Criteria- Phase 1b(From treatment initiation till study completion)
- SSA: Pre- and Post-dose Concentrations of Elranatamab- Phase 1b(From treatment initiation till study completion)
- SSA: Trough Serum Concentrations of Nirogacestat- Phase 1b(From treatment initiation till study completion)
- SSA: Number of Participants With Anti-drug Antibodies (ADA)- Phase 1b(From treatment initiation till study completion)
- SSB: OS- Phase 1b Dose Escalation(From treatment initiation till study completion)
- SSB: Number of Participants With TEAEs and Treatment Related TEAEs- Phase 1b(From treatment initiation till study completion)
- SSB: Number of Participants With Severity of Adverse Events According to CRS Graded According to ASTCT Grading Criteria 2019- Phase 1b Dose Escalation(From treatment initiation till study completion)
- SSB: Number of Participants With Severity of Adverse Events According to ICANS Graded According to ASTCT Grading Criteria 2019- Phase 1b Dose Escalation(From treatment initiation till study completion)
- SSB: Number of Participants With Laboratory Abnormalities- Phase 1b Dose Escalation(From treatment initiation till study completion)
- SSB: ORR as Per IMWG Criteria as Determined by Investigator- Phase 1b Dose Escalation(From treatment initiation till study completion)
- SSB: CRR as Per IMWG Criteria as Determined by Investigator- Phase 1b Dose Escalation(From treatment initiation till study completion)
- SSB: TTR as Per IMWG Criteria as Determined by Investigator- Phase 1b Dose Escalation(From treatment initiation till study completion)
- SSB: DOR as Per IMWG Criteria as Determined by Investigator- Phase 1b Dose Escalation(From treatment initiation till study completion)
- SSB: DOCR as Per IMWG Criteria as Determined by Investigator- Phase 1b Dose Escalation(From treatment initiation till study completion)
- SSB: PFS as Per IMWG Criteria as Determined by Investigator- Phase 1b Dose Escalation(From treatment initiation till study completion)
- SSB: MRD Negativity Rate as Per IMWG Criteria- Phase 1b Dose Escalation(From treatment initiation till study completion)
- SSB: Pre- and Post-dose Concentrations of Elranatamab- Phase 1b Dose Escalation(From treatment initiation till study completion)
- SSB: Trough Serum Concentrations of Lenalidomide- Phase 1b Dose Escalation(From treatment initiation till study completion)
- SSA: Number of Participants With ADA- Phase 1b Dose Escalation(From treatment initiation till study completion)
- SSB: Number of Participants With NAb- Phase 1b Dose Escalation(From treatment initiation till study completion)