MAGNETISMM-1 A PHASE I, OPEN LABEL STUDY TO EVALUATE THE SAFETY, PHARMACOKINETIC, PHARMACODYNAMIC AND CLINICAL ACTIVITY OF ELRANATAMAB (PF-06863135), A B-CELL MATURATION ANTIGEN (BCMA) - CD3 BISPECIFIC ANTIBODY, AS A SINGLE AGENT AND IN COMBINATION WITH IMMUNOMODULATORY AGENTS IN PATIENTS WITH RELAPSED/REFRACTORY ADVANCED MULTIPLE MYELOMA (MM)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 101
- 试验地点
- 37
- 主要终点
- Part 1: Number of Participants With Drug Limiting Toxicities (DLTs) Graded According to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version (v)4.03
研究概览
简要总结
To assess the safety and tolerability at increasing dose levels of PF-06863135 in patients with relapse/ refractory multiple myeloma in order to determine the maximum tolerated dose and select the recommended Phase 2 dose.
详细描述
Study C1071001 is a Phase 1, open label, multi dose, multi center, dose escalation, safety, pharmacokinetic (PK) and pharmacodynamic study of PF-06863135 in adult patients with advanced multiple myeloma who have relapsed from or are refractory to standard therapy. This is a two part study; Part 1 will assess the safety and tolerability of increasing dose levels of PF-06863135 and Part 2 will evaluate safety and anti-myeloma activity of PF-06863135 at the RP2Ds determined in Part 1.
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
- •Progressed or are intolerant of established therapies including proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody
- •Performance Status of 0- 1 ( Performance Score 2 is permitted only if due to underlying myeloma)
- •Adequate bone marrow, hematological, kidney and liver function
- •Resolved acute effects of any prior therapy to baseline severity
- •Not pregnant
排除标准
- •Recent history of other malignancies
- •History of active autoimmune disorders
- •Any form of primary immunodeficiency
- •Active and clinically significant bacterial, fungal, or viral infection
- •Evidence of active mucosal or internal bleeding
- •History of severe immune-mediated adverse event with prior immunomodulatory treatment
- •Major surgery within 4 weeks of study treatment start
- •Radiation therapy within 2 weeks of study treatment start
- •History of stem cell transplant (autologous or allogeneic) within 100 days prior to study enrollment
- •Donor Lymphocyte Infusion (DLI) within 30 days prior to study entry
- •Less than 30 days since last dose of antibody based therapies or less than 5 half-lives since last dose of previous therapy
- •Requirement for systemic immune suppressive medication except as permitted in the protocol
- •Current requirement for chronic blood product support
研究组 & 干预措施
PF-06863135
BCMA-CD3 bispecific antibody
干预措施: PF-06863135 monotherapy IV or SC (Drug)
PF-06863135 + dexamethasone
BCMA-CD3 bispecific antibody + dexamethasone
干预措施: PF-06863135 + dexamethasone (Drug)
PF-06863135 + lenalidomide
BCMA-CD3 bispecific antibody + lenalidomide
干预措施: PF-06863135 + lenalidomide (Drug)
PF-06863135 + pomalidomide
BCMA-CD3 bispecific antibody + pomalidomide
干预措施: PF-06863135 + pomalidomide (Drug)
结局指标
主要结局
Part 1: Number of Participants With Drug Limiting Toxicities (DLTs) Graded According to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version (v)4.03
时间窗: Cycle 1 (21 Days)
Hematological: Grade 4 neutropenia lasting \>5 days; Febrile neutropenia \<1000/mm\^3 with a single temperature of \>38.3 degree Celsius (C) or a sustained temperature of \>=38 degree C for more than one hour; grade \>=3 neutropenia with infection; grade 4 thrombocytopenia; grade 3 thrombocytopenia with \>= Grade 2 bleeding. Non-hematological: grade 4 adverse events (AEs); Grade 3 AE lasting \>=5 days despite optimal supportive care, with exception of AE attributed to cytokine release syndrome (CRS) event; grade 3 CRS, except those CRS that had a) not been maximally treated or b) improved to \<=grade 1 within 48 hours; grade 4 CRS; confirmed drug-induced liver injury (DILI) meeting Hy's law criteria; grade 4 laboratory abnormalities deemed clinically significant by the investigator reported Grade 4 AE; clinically important or persistent toxicities that were not included in above criteria were also be considered a DLT following review by the investigators and the sponsor.
Part 2: Objective Response Rate (ORR) as Per International Myeloma Working Group (IMWG) Criteria
时间窗: From the first dose of study treatment until the first documented sCR or CR or PR or VGPR or new anti-cancer therapies or death, whichever occurred first (maximum up to 34.3 months)
ORR per IMWG criteria: percentage of participants with best overall response (BOR) of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). sCR: complete response plus normal free light chain (FLC) ratio and absence of clonal cells in bone marrow biopsy by immunohistochemistry; CR: negative immunofixation on serum and urine and disappearance of any soft tissue plasmacytomas and \<5% plasma cells in bone marrow aspirates. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>=90% reduction in serum M-protein plus urine M-protein level \<100 mg/24 hr. PR: \>=50% reduction of serum M-protein and reduction in 24 hrs urinary M-protein by \>=90% or to \<200 mg/24 hr. If serum and urine M-protein were unmeasurable, \>=50% decrease in difference between involved and uninvolved FLC levels required in place of the M-protein criteria.
Part 2: Duration of Response (DOR) as Per IMWG Criteria
时间窗: From the first documentation of objective tumor response to first documentation of objective tumor progression or new anti-cancer therapies or death, whichever occurred first, (maximum up to 34.3 months)
DOR per IMWG criteria:time from first documentation of objective tumor (OT)response to first documentation of OTprogression or to death due to any cause, whichever occurred first.sCR: CR plus normal FLC ratio \& absence of clonal cells in bone marrow biopsy by immunohistochemistry;CR:Negative immunofixation on serum \& urine \& disappearance of any soft tissue plasmacytomas\&\<5% plasma cells in bone marrow aspirates.VGPR: serum \& urine M-protein(Mp) detectable by immunofixation but not on electrophoresis or \>=90% reduction in serum Mp plus urine Mp level \<100 mg/24 hr. PR: \>=50% reduction of serum Mp \& reduction in 24 hrs urinary Mp by \>=90% or to \<200 mg/24 hr.If serum \& urine Mp were unmeasurable, \>=50% decrease in difference between involved \& uninvolved FLC levels required in place of Mp criteria. Progression: appearance of local, regional or distant disease of same type after CR or progression of pre-existing lesions. It did not include second primary malignancies of unrelated types.
次要结局
- Part 1: Number of Participants With Treatment Emergent Adverse Events (AEs), Serious AEs, Treatment Related AEs, Grade 3 or 4 AEs and Grade 5 AEs as Graded by NCI CTCAE v4.03(From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to of 43.3 months))
- Part 1: Number of Participants With Shifts From Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post-Baseline in Hematology Parameters(From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to of 43.3 months))
- Part 1: Number of Participants With Shifts From Grade <= 2 at Baseline to Grade 3 or 4 Post-Baseline in Clinical Chemistry Parameters(From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to of 43.3 months))
- Part 1: Number of Participants With Shifts From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline in Urinalysis(From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to of 43.3 months))
- Part 1: ORR as Per IMWG Criteria(From the first dose of study treatment until the first documented sCR or CR or PR or VGPR or new anti-cancer therapies or death, whichever occurred first (maximum up to 63.31 months))
- Part 1: Time to Response (TTR) as Per IMWG Criteria(From the first dose of study treatment until the first documented sCR or CR or PR or VGPR or new anti-cancer therapies or death, whichever occurred first (maximum up to 63.31 months))
- Part 1: Complete Response Rate (CRR) as Per IMWG Criteria(From the first dose of study treatment until the first documented sCR or CR or new anti-cancer therapies or death, whichever occurred first (maximum up to 63.31 months))
- Part 1: DOR as Per IMWG Criteria(From the first documentation of objective tumor response to first documentation of objective tumor progression or new anti-cancer therapies or death, whichever occurred first, (maximum up to 63.31 months))
- Part 1: Duration of Complete Response (DoCR) as Per IMWG Criteria(From the first documentation of complete response to the first documentation of tumor progression or death, whichever occurred first (maximum up to 63.31 months))
- Part 1: Duration of Stable Disease (DOSD) as Per IMWG Criteria(Time from the first documentation of objective stable disease to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first (maximum up to 63.31 months))
- Part 1: Progression Free Survival (PFS) as Per IMWG Criteria(From start date of study treatment to date of first documentation of progression or death due to any cause, whichever occurred first (maximum up to 63.31 months))
- Part 1: Overall Survival (OS)(Time from start date of study treatment to date of death due to any cause or last-known-alive date, whichever occurred first (maximum up to 63.31 months))
- Part 1: Percentage of Participants With Negative Minimal Residual Disease (MRD) Using IMWG MRD Criteria(Anytime from date of first dose until the first documentation of confirmed PD, death or start of new anticancer therapy, whichever occurred first (maximum up to 63.31 months))
- Part 1: Maximum Observed Concentration (Cmax) of PF-06863135(0 hours (h) on Day 1 of Cycle (C) 0; 0, 2 and 4h on Day 1 of C1 and C2)
- Part 1: Area Under the Concentration-Time Profile From Time 0 to End of Dosing Interval (AUCtau)(0 hours (h) on Day 1 of Cycle (C) 0; 0, 2 and 4h on Day 1 of C1 and C2)
- Part 1C and Part 1D: Plasma Concentration of Lenalidomide and Pomalidomide(Cycle 1 (0 hours post dose on Day 1, 8 and 15); Cycle 2 (0 hours on Day 15))
- Part 1: Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (NAb) Against PF-06863135(From first dose of the study treatment (Day 1) up to end of study treatment (maximum up to 63.31 months))
- Part 1: Concentration of Soluble Cytokines in Serum(Part 1: C1 (0, 2, 4 & 8 hours [h] post dose on Day [D] 1, 24h post dose on D2, 72h post dose on D3); Part 1.1, 1C & 1D: C0 (0, 2, 4 & 8h post dose on D1, 24h post dose on D2); C1 (0, 2, 4 & 8h post dose on D1, 24h post dose on D2, 72h post dose on D3))
- Part 2: Number of Participants With AEs, Serious AEs, Treatment Related AEs, Grade 3 or 4 AEs and Grade 5 AEs as Graded by NCI CTCAE v4.03(From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to of 32.3 months))
- Part 2: Number of Participants With Shifts From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline in Hematology Parameters(From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to of 32.3 months))
- Part 2: Number of Participants With Shifts From Grade <= 2 at Baseline to Grade 3 or 4 Post-Baseline in Clinical Chemistry Parameters(From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to of 32.3 months))
- Part 2: Number of Participants With Shifts From Grade <=2 to Grade 3 or 4 Post-Baseline in Urinalysis(From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to of 32.3 months))
- Part 2: CRR as Per IMWG Criteria(From the first dose of study treatment until the first documented sCR or CR or new anti-cancer therapies or death, whichever occurred first (maximum up to 34.3 months))
- Part 2: DoCR as Per IMWG Criteria(From the first documentation of complete response to the first documentation of tumor progression or death, whichever occurred first (maximum up to 34.3 months))
- Part 2: TTR as Per IMWG Criteria(From the first dose of study treatment until the first documented sCR or CR or PR or VGPR or new anti-cancer therapies or death, whichever occurred first (maximum up to 34.3 months))
- Part 2: DOSD as Per IMWG Criteria(Time from the first documentation of objective stable disease to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first (maximum up to 34.3 months))
- Part 2: PFS as Per IMWG Criteria(From start date of study treatment to date of first documentation of progression or death due to any cause, whichever occurred first (maximum up to 34.3 months))
- Part 2: OS(Time from start date of study treatment to date of death due to any cause or last-known-alive date, whichever occurred first (maximum up to 34.3 months))
- Part 2: Percentage of Participants With Negative MRD After Treatment With PF-06863135 Using IMWG MRD Criteria(Anytime from date of first dose until the first documentation of confirmed PD, death or start of new anticancer therapy whichever occurred first (maximum up to 34.3 months))
- Part 2: Number of Participants With ADA and NAb Against PF-06863135(From first dose of the study treatment (Day 1) up to end of study treatment (maximum up to 34.3 months))
- Part 2: Concentration of Soluble Cytokines in Serum(Cycle 0 (0, 2, 4 and 8 hours post dose on Day 1, 24 hours post dose on Day 2); Cycle 1 (0, 2, 4 and 8 hours post dose on Day 1, 24 hours post dose on Day 2, 72 hours post dose on Day 3))