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
- Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) as Per International Myeloma Working Group (IMWG) Criteria
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
- 干预性
- 分配方式
- 不适用
- 干预模型
- 单组
- 主要目的
- 治疗
- 盲法
- 开放（无盲法）
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)
方案终点
主要结局
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 (PD), death, start of new anticancer therapy, whichever occurred first (approximately up to 16 months)
ORR: Percentage of participants with best overall response (BOR) of confirmed stringent complete response (sCR), CR, very good partial response (VGPR) or PR per IMWG criteria. sCR: CR and normal serum free light chain (sFLC) ratio and 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.
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.
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.
次要结局
- Serum Concentration of Free Elranatamab(Predose, 6, 24, and 48 hours post dose on Cycle (C) 1 Day (D) 1; Predose and 24 hours post dose on C1D4; Predose and 6 hours post dose on C1D8; Predose on C1D15; C1D22; C2D1; C3D1; C4D1; C7D1; and C10D1)
- Duration of Response (DOR) as Per IMWG Criteria by BICR(From first documentation of objective response until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurred first, or censoring date (up to 38.8 months of follow-up))
- DOR as Per IMWG Criteria by Investigator Assessment(From first documentation of objective response until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurred first, or censoring date (up to 38.8 months of follow-up))
- Complete Response Rate (CRR) as Per IMWG Criteria by BICR(From date of first dose until confirmed PD, death or start of new anticancer therapy, whichever occurred first (up to 38.8 months of follow-up))
- CRR as Per IMWG Criteria by Investigator Assessment(From date of first dose until confirmed PD, death or start of new anticancer therapy, whichever occurred first (up to 38.8 months of follow-up))
- ORR as Per IMWG Criteria by Investigator Assessment(From date of first dose until confirmed PD, death due to any cause, or start of new anticancer therapy, whichever occurred first (up to 38.8 months of follow-up))
- Duration of Complete Response (DOCR) as Per IMWG Criteria by BICR(From the first documentation of sCR/CR, until confirmed PD, or death due to any cause, whichever occurred first (up to 38.8 months of follow-up))
- 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 38.8 months of follow-up))
- Progression Free Survival (PFS) as Per IMWG Criteria by BICR(From date of first dose until confirmed PD per IMWG criteria or death due to any cause, or start of new anticancer therapy, whichever occurred first, or censoring date (up to 38.8 months of follow-up))
- PFS as Per IMWG Criteria by Investigator Assessment(From date of first dose until confirmed PD per IMWG criteria or death due to any cause, or start of new anticancer therapy, whichever occurred first, or censoring date (up to 38.8 months of follow-up))
- Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) of Free Elranatamab(Cycle 1: Pre-dose on Day 1, 4, 8, 6, 24, 48, 120, and 198 hours post-dose; Day 15, 22: pre-dose; Cycles 2, 3 ,4, 7: pre-dose (1 cycle =28 days))
- Overall Survival (OS)(From the date of first dose until death due to any cause or censoring date (up to 38.8 months of follow-up))
- Time-to-Response (TTR) as Per IMWG Criteria by BICR(From date of first dose until confirmed PD per IMWG criteria, death, start of new anticancer therapy, whichever occurred first (approximately up to 16 months))
- TTR as Per IMWG Criteria by Investigator Assessment(From date of first dose until confirmed PD per IMWG criteria, death, start of new anticancer therapy, whichever occurred first (up to 38.8 months of follow-up))
- Minimal Residual Disease (MRD) Negativity Rate Per IMWG Sequencing Criteria by BICR(From date of first dose until confirmed PD per IMWG criteria, death, start of new anticancer therapy, whichever occurred first (up to 38.8 months of follow-up))
- MRD Negativity Rate Per IMWG Sequencing Criteria by Investigator Assessment(From date of first dose until confirmed PD per IMWG criteria, death, start of new anticancer therapy, whichever occurred first (up to 38.8 months of follow-up))
- 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 of study intervention up to 90 days after last dose of study intervention or start of new anticancer therapy whichever occurred first (up to 38.8 months of follow-up))
- Number of Participants With Cytokine Release Syndrome (CRS) of Any Grade According to American Society for Transplantation and Cellular Therapy (ASTCT) Criteria(From the date of first dose of study intervention up to 90 days after last dose of study intervention or start of new anticancer therapy whichever occurred first (up to 38.8 months of follow-up))
- Number of Participants With Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) of Any Grade According to ASTCT Criteria(From the date of first dose of study intervention up to 90 days after last dose of study intervention or start of new anticancer therapy whichever occurred first (up to 38.8 months of follow-up))
- Maximum Serum Concentration (Cmax) of Free Elranatamab(Cycle 1: Pre-dose on Day 1, 4, 8, 6, 24, 48, 120, and 198 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 on Day 1, 4, 8, 6, 24, 48, 120, and 198 hours post-dose; Day 15, 22: pre-dose; Cycles 2, 3 ,4, 7: pre-dose (1 cycle =28 days))
- Percentage of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) Against Elranatamab(From the date of first dose of study intervention up to 90 days after last dose of study intervention or start of new anticancer therapy whichever occurred first (up to 38.8 months of follow-up))
- Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life of Cancer Participants Core Module (EORTC QLQ-C30) at Cycle 9 Day 1(Baseline (prior to the date of the first dose of study intervention), and Cycle 9 Day 1)
- Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Myeloma-Specific Module (EORTC QLQ-MY20) at Cycle 9 Day 1(Baseline (prior to the date of the first dose of study intervention), and Cycle 9 Day 1)
- Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Chemotherapy-Induced Peripheral Neuropathy (EORTC QLQ CIPN20) at Cycle 9 Day 1(Baseline (prior to the date of the first dose of study intervention), and Cycle 9 Day 1)
- Change From Baseline in EuroQol Five Dimensions Questionnaire (EQ-5D) Index Score and in EQ-5D Visual Analogue Score (EQ-VAS) at Cycle 9 Day 1(Baseline (prior to the date of the first dose of study intervention), and Cycle 9 Day 1)
- 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)
试验结果
结果已于 2024-09-19 在 ClinicalTrials.gov 公示。 在 ClinicalTrials.gov 查看
受试者流程
入组 39 人 · 完成 0 人
主要终点
Phase 1b: Number of Participants With Dose-Limiting Toxicities (DLT)
Participants · 时间窗: Cycle 1 (28 days)
| Phase 1b （n=6） |
|---|
| 1 |
DLT evaluable analysis set included all participants enrolled to Phase 1b part and who had a DLT in the DLT observation period or completed the DLT observation period without DLT. Participants without DLTs and without the minimum required exposure for reasons other than treatment-related toxicity were not evaluable for DLTs and were replaced.
Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) as Per International Myeloma Working Group (IMWG) Criteria
Percentage of participants · 95% Confidence Interval · 时间窗: From date of first dose until confirmed disease progression (PD), death, start of new anticancer therapy, whichever occurred first (approximately up to 16 months)
| Phase 1b （n=8） | Phase 2 （n=30） | Phase 1b + Phase 2 （n=38） |
|---|---|---|
| 37.5 (8.5–75.5) | 53.3 (34.3–71.7) | 50.0 (33.4–66.6) |
The primary analysis of ORR as planned per protocol included participants who started with the recommended phase 2 dose \[RP2D\] (including the participants from both Phase 1b and Phase 2 parts). Safety analysis set included all enrolled participants who received at least 1 dose of study intervention. Data that was collected and was final till the primary completion date (PCD) is reported in this outcome measure.
p = 0.0076 · Exact binomial test
其他终点（26）
Duration of Response (DOR) as Per IMWG Criteria by BICR
Months · 95% Confidence Interval · 时间窗: From first documentation of objective response until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurred first, or censoring date (up to 38.8 months of follow-up)
| Phase 1b （n=3） | Phase 2 （n=16） | Phase 1b + Phase 2 （n=19） |
|---|---|---|
| 8.7 (7.4–NA) | 13.7 (2.8–NA) | 8.7 (3.7–NA) |
Safety analysis set included all enrolled participants who received at least 1 dose of study intervention. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
Phase 1b: The upper limit of 95% confidence interval (CI) could not be estimated due to insufficient number of participants with event.
Phase 2: The upper limit of 95% CI could not be estimated due to insufficient number of participants with event.
Phase 1b + Phase 2: The upper limit of 95% CI could not be estimated due to insufficient number of participants with event.
DOR as Per IMWG Criteria by Investigator Assessment
Months · 95% Confidence Interval · 时间窗: From first documentation of objective response until confirmed PD or death due to any cause, or start of new anticancer therapy, whichever occurred first, or censoring date (up to 38.8 months of follow-up)
| Phase 1b （n=3） | Phase 2 （n=14） | Phase 1b + Phase 2 （n=17） |
|---|---|---|
| 8.7 (7.5–NA) | NA (3.7–NA) | 18.5 (6.9–NA) |
Safety analysis set included all enrolled participants who received at least 1 dose of study intervention. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
Phase 1b: The upper limit of 95% CI could not be estimated due to insufficient number of participants with event.
Phase 2: The median and upper limit of 95% CI could not be estimated due to insufficient number of participants with event.
Phase 1b + Phase 2: The upper limit of 95% CI could not be estimated due to insufficient number of participants with event.
Complete Response Rate (CRR) as Per IMWG Criteria by BICR
Percentage of participants · 95% Confidence Interval · 时间窗: From date of first dose until confirmed PD, death or start of new anticancer therapy, whichever occurred first (up to 38.8 months of follow-up)
| Phase 1b （n=8） | Phase 1b + Phase 2 （n=38） | Phase 2 （n=30） |
|---|---|---|
| 25.0 (3.2–65.1) | 21.1 (9.6–37.3) | 20.0 (7.7–38.6) |
Safety analysis set included all enrolled participants who received at least 1 dose of study intervention.
CRR as Per IMWG Criteria by Investigator Assessment
Percentage of participants · 95% Confidence Interval · 时间窗: From date of first dose until confirmed PD, death or start of new anticancer therapy, whichever occurred first (up to 38.8 months of follow-up)
| Phase 1b （n=8） | Phase 1b + Phase 2 （n=38） | Phase 2 （n=30） |
|---|---|---|
| 25.0 (3.2–65.1) | 18.4 (7.7–34.3) | 16.7 (5.6–34.7) |
Safety analysis set included all enrolled participants who received at least 1 dose of study intervention.
ORR as Per IMWG Criteria by Investigator Assessment
Percentage of participants · 95% Confidence Interval · 时间窗: From date of first dose until confirmed PD, death due to any cause, or start of new anticancer therapy, whichever occurred first (up to 38.8 months of follow-up)
| Phase 1b （n=8） | Phase 1b + Phase 2 （n=38） | Phase 2 （n=30） |
|---|---|---|
| 37.5 (8.5–75.5) | 44.7 (28.6–61.7) | 46.7 (28.3–65.7) |
Safety analysis set included all enrolled participants who received at least 1 dose of study intervention.
Duration of Complete Response (DOCR) as Per IMWG Criteria by BICR
Months · 95% Confidence Interval · 时间窗: From the first documentation of sCR/CR, until confirmed PD, or death due to any cause, whichever occurred first (up to 38.8 months of follow-up)
| Phase 1b （n=2） | Phase 1b + Phase 2 （n=8） | Phase 2 （n=6） |
|---|---|---|
| NA (NA–NA) | NA (1.6–NA) | NA (1.6–NA) |
Safety analysis set included all enrolled participants who received at least 1 dose of study intervention. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
Phase 1b: Summary statistics was note reported for \<3 participants, individual values were 5.55, and 4.01 months.
Phase 1b + Phase 2: The median and upper limit of 95% CI could not be estimated due to insufficient number of participants with event.
Phase 2: The median and upper limit of 95% CI could not be estimated due to insufficient number of participants with event.
DOCR as Per IMWG Criteria by Investigator Assessment
Months · 95% Confidence Interval · 时间窗: From the first documentation of sCR/CR, until confirmed PD per IMWG criteria, or death due to any cause, whichever occurred first (up to 38.8 months of follow-up)
| Phase 1b （n=2） | Phase 1b + Phase 2 （n=7） | Phase 2 （n=5） |
|---|---|---|
| NA (NA–NA) | NA (1.7–NA) | NA (1.7–NA) |
Safety analysis set included all enrolled participants who received at least 1 dose of study intervention. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
Phase 1b: Summary statistics was not reported for \<3 participants, individual values were 17.48, and 4.01 months.
Phase 1b + Phase 2: The median and upper limit of 95% CI could not be estimated due to insufficient number of participants with event.
Phase 2: The median and upper limit of 95% CI could not be estimated due to insufficient number of participants with event.
Progression Free Survival (PFS) as Per IMWG Criteria by BICR
Months · 95% Confidence Interval · 时间窗: From date of first dose until confirmed PD per IMWG criteria or death due to any cause, or start of new anticancer therapy, whichever occurred first, or censoring date (up to 38.8 months of follow-up)
| Phase 1b （n=8） | Phase 1b + Phase 2 （n=38） | Phase 2 （n=30） |
|---|---|---|
| 1.8 (0.6–9.9) | 5.7 (2.2–8.0) | 5.7 (2.3–8.0) |
Safety analysis set included all enrolled participants who received at least 1 dose of study intervention.
PFS as Per IMWG Criteria by Investigator Assessment
Months · 95% Confidence Interval · 时间窗: From date of first dose until confirmed PD per IMWG criteria or death due to any cause, or start of new anticancer therapy, whichever occurred first, or censoring date (up to 38.8 months of follow-up)
| Phase 1b （n=8） | Phase 2 （n=30） | Phase 1b + Phase 2 （n=38） |
|---|---|---|
| 1.8 (0.6–9.9) | 5.7 (2.3–NA) | 5.7 (2.2–9.9) |
Safety analysis set included all enrolled participants who received at least 1 dose of study intervention.
Phase 2: Upper limit of 95% CI could not be estimated due to insufficient number of participants with event.
Overall Survival (OS)
Months · 95% Confidence Interval · 时间窗: From the date of first dose until death due to any cause or censoring date (up to 38.8 months of follow-up)
| Phase 1b （n=8） | Phase 1b + Phase 2 （n=38） | Phase 2 （n=30） |
|---|---|---|
| 4.0 (1.2–14.4) | 9.0 (4.0–14.9) | 9.0 (5.5–16.7) |
Safety analysis set included all enrolled participants who received at least 1 dose of study intervention.
Time-to-Response (TTR) as Per IMWG Criteria by BICR
Months · Full Range · 时间窗: From date of first dose until confirmed PD per IMWG criteria, death, start of new anticancer therapy, whichever occurred first (approximately up to 16 months)
| Phase 1b （n=3） | Phase 1b + Phase 2 （n=19） | Phase 2 （n=16） |
|---|---|---|
| 2.04 (1.15–4.73) | 1.51 (0.95–5.52) | 1.45 (0.95–5.52) |
Safety analysis set included all enrolled participants who received at least 1 dose of study intervention. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. Data that was collected and was final till the PCD is reported in this outcome measure.
TTR as Per IMWG Criteria by Investigator Assessment
Months · Full Range · 时间窗: From date of first dose until confirmed PD per IMWG criteria, death, start of new anticancer therapy, whichever occurred first (up to 38.8 months of follow-up)
| Phase 1b （n=3） | Phase 1b + Phase 2 （n=17） | Phase 2 （n=14） |
|---|---|---|
| 2.04 (1.15–2.79) | 1.22 (0.95–4.01) | 1.2 (0.95–4.01) |
Safety analysis set included all enrolled participants who received at least 1 dose of study intervention. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
Minimal Residual Disease (MRD) Negativity Rate Per IMWG Sequencing Criteria by BICR
Percentage of participants · 95% Confidence Interval · 时间窗: From date of first dose until confirmed PD per IMWG criteria, death, start of new anticancer therapy, whichever occurred first (up to 38.8 months of follow-up)
| Phase 1b （n=2） | Phase 1b + Phase 2 （n=7） | Phase 2 （n=5） |
|---|---|---|
| 100.0 (15.81–100.0) | 85.7 (42.13–99.64) | 80.0 (28.36–99.49) |
Safety analysis set included all enrolled participants who received at least 1 dose of study intervention. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
MRD Negativity Rate Per IMWG Sequencing Criteria by Investigator Assessment
Percentage of participants · 95% Confidence Interval · 时间窗: From date of first dose until confirmed PD per IMWG criteria, death, start of new anticancer therapy, whichever occurred first (up to 38.8 months of follow-up)
| Phase 1b （n=2） | Phase 1b + Phase 2 （n=7） | Phase 2 （n=5） |
|---|---|---|
| 100.0 (15.81–100.0) | 85.7 (42.13–99.64) | 80.0 (28.36–99.49) |
Safety analysis set included all enrolled participants who received at least 1 dose of study intervention. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
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
Participants · 时间窗: From the date of first dose of study intervention up to 90 days after last dose of study intervention or start of new anticancer therapy whichever occurred first (up to 38.8 months of follow-up)
| 分类 | Phase 1b （n=8） | Phase 1b + Phase 2 （n=38） | Phase 2 （n=30） |
|---|---|---|---|
| Participants With TEAEs | 8 | 38 | 30 |
| Participants With Serious TEAEs | 6 | 28 | 22 |
| Participants with Maximum Grade 3 or 4 TEAEs | 4 | 24 | 20 |
| Participants with Maximum Grade 5 TEAEs | 4 | 13 | 9 |
| Participants With Treatment Related TEAEs | 7 | 37 | 30 |
| Participants With Treatment Related Serious TEAEs | 4 | 21 | 17 |
| Participants with Maximum Grade 3 or 4 Treatment Related TEAEs | 5 | 27 | 22 |
| Participants with Maximum Grade 5 Treatment Related TEAEs | 1 | 5 | 4 |
Safety analysis set included all enrolled participants who received at least 1 dose of study intervention.
Number of Participants With Cytokine Release Syndrome (CRS) of Any Grade According to American Society for Transplantation and Cellular Therapy (ASTCT) Criteria
Participants · 时间窗: From the date of first dose of study intervention up to 90 days after last dose of study intervention or start of new anticancer therapy whichever occurred first (up to 38.8 months of follow-up)
| Phase 1b （n=8） | Phase 1b + Phase 2 （n=38） | Phase 2 （n=30） |
|---|---|---|
| 3 | 19 | 16 |
Safety analysis set included all enrolled participants who received at least 1 dose of study intervention.
Number of Participants With Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) of Any Grade According to ASTCT Criteria
Participants · 时间窗: From the date of first dose of study intervention up to 90 days after last dose of study intervention or start of new anticancer therapy whichever occurred first (up to 38.8 months of follow-up)
| Phase 1b （n=8） | Phase 1b + Phase 2 （n=38） | Phase 2 （n=30） |
|---|---|---|
| 0 | 0 | 0 |
Safety analysis set included all enrolled participants who received at least 1 dose of study intervention.
Maximum Serum Concentration (Cmax) of Free Elranatamab
Microgram per milliliter · Geometric Coefficient of Variation · 时间窗: Cycle 1: Pre-dose on Day 1, 4, 8, 6, 24, 48, 120, and 198 hours post-dose; Day 15, 22: pre-dose; Cycles 2, 3 ,4, 7: pre-dose (1 cycle =28 days)
| Phase 2 （n=6） | Phase 1b （n=7） | Phase 1b + Phase 2 （n=13） |
|---|---|---|
| 0.8039 (24) | 0.8762 (66) | 0.842 (48) |
Pharmacokinetic (PK) parameter analysis set included all participants enrolled and treated who had at least 1 of the PK parameters of primary interest in the single dose and/or multiple-dose PK part. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
Time To Maximum Serum Concentration (Tmax) of Free Elranatamab
Days · Full Range · 时间窗: Cycle 1: Pre-dose on Day 1, 4, 8, 6, 24, 48, 120, and 198 hours post-dose; Day 15, 22: pre-dose; Cycles 2, 3 ,4, 7: pre-dose (1 cycle =28 days)
| Phase 2 （n=6） | Phase 1b （n=7） | Phase 1b + Phase 2 （n=13） |
|---|---|---|
| 8.0 (6.94–11.0) | 7.0 (3.93–9.97) | 7.0 (3.93–11.0) |
PK parameter analysis set included all participants enrolled and treated who had at least 1 of the PK parameters of primary interest in the single dose and/or multiple-dose PK part. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) of Free Elranatamab
Microgram*day per milliliter · Geometric Coefficient of Variation · 时间窗: Cycle 1: Pre-dose on Day 1, 4, 8, 6, 24, 48, 120, and 198 hours post-dose; Day 15, 22: pre-dose; Cycles 2, 3 ,4, 7: pre-dose (1 cycle =28 days)
| Phase 2 （n=6） | Phase 1b （n=7） | Phase 1b + Phase 2 （n=13） |
|---|---|---|
| 3.864 (37) | 3.482 (74) | 3.653 (56) |
PK parameter analysis set included all participants enrolled and treated who had at least 1 of the PK parameters of primary interest in the single dose and/or multiple-dose PK part. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
Serum Concentration of Free Elranatamab
Nanogram per milliliter · Geometric Coefficient of Variation · 时间窗: Predose, 6, 24, and 48 hours post dose on Cycle (C) 1 Day (D) 1; Predose and 24 hours post dose on C1D4; Predose and 6 hours post dose on C1D8; Predose on C1D15; C1D22; C2D1; C3D1; C4D1; C7D1; and C10D1
| 分类 | Phase 2 （n=30） | Phase 1b （n=8） | Phase 1b + Phase 2 （n=38） |
|---|---|---|---|
| Predose on C1D1 | NA (NA) | NA (NA) | NA (NA) |
| 6 hours post dose on C1D1 | 80.02 (39) | 79.54 (81) | 79.85 (52) |
| 24 hours post dose on C1D1 | 131.3 (41) | 144.1 (70) | 133.9 (47) |
| 48 hours post dose on C1D1 | 285.3 (33) | 230.1 (56) | 252.3 (47) |
| Predose on C1D4 | 288.2 (40) | 272.1 (43) | 285.1 (40) |
| 24 hours post dose on C1D4 | 445.3 (42) | 628.7 (94) | 475.4 (54) |
| Predose on C1D8 | 757.0 (53) | 697.3 (72) | 743.7 (57) |
| 6 hours post dose on C1D8 | 1148 (52) | 1026 (81) | 1121 (58) |
| Predose on C1D15 | 3097 (68) | 2264 (104) | 2914 (75) |
| Predose on C1D22 | 4511 (104) | 3569 (128) | 4311 (107) |
| Predose on C2D1 | 7960 (88) | 7423 (48) | 7891 (82) |
| Predose on C3D1 | 11470 (111) | NA (NA) | 11030 (102) |
| Predose on C4D1 | 10980 (348) | NA (NA) | 11580 (282) |
| Predose on C7D1 | 18410 (67) | 68300 | 23930 (93) |
| Predose on C10D1 | 13430 (29) | 34200 | 15690 (49) |
PK concentration analysis set included all participants enrolled and treated who had at least 1 PK concentration in the single-dose and/or multiple-dose PK part. Here, "Number Analyzed" signified participants evaluable for specified rows.
Phase 2: The geometric mean and geometric coefficient of variation could not be estimated as the concentration was below the lower limit of quantification.
Phase 1b: The geometric mean and geometric coefficient of variation could not be estimated as the concentration was below the lower limit of quantification.
Phase 1b + Phase 2: The geometric mean and geometric coefficient of variation could not be estimated as the concentration was below the lower limit of quantification.
Phase 1b: Summary statistics were not reported for timepoints with less than 3 evaluable concentrations; individual values were 5740 and 13200 nanogram per milliliter.
Phase 1b: Summary statistics were not reported for timepoints with less than 3 evaluable concentrations; individual values were 15000 and 16900 nanogram per milliliter.
Percentage of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies (NAb) Against Elranatamab
Percentage of participants · 时间窗: From the date of first dose of study intervention up to 90 days after last dose of study intervention or start of new anticancer therapy whichever occurred first (up to 38.8 months of follow-up)
| 分类 | Phase 2 （n=25） | Phase 1b （n=6） | Phase 1b + Phase 2 （n=31） |
|---|---|---|---|
| ADA | 4.0 | 0.0 | 3.2 |
| NAb | 4.0 | 0.0 | 3.2 |
The immunogenicity analysis set was a subset of the safety analysis set and included participants who had at least one sample tested for ADA. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life of Cancer Participants Core Module (EORTC QLQ-C30) at Cycle 9 Day 1
Units on a scale · Standard Deviation · 时间窗: Baseline (prior to the date of the first dose of study intervention), and Cycle 9 Day 1
| 分类 | Phase 2 （n=7） | Phase 1b （n=3） | Phase 1b + Phase 2 （n=10） |
|---|---|---|---|
| Global QOL | 1.19 (13.968) | 5.56 (4.811) | 2.5 (11.818) |
| Physical Functioning | -11.43 (24.859) | 20.0 (29.059) | -2.0 (28.812) |
| Role Functioning | -14.29 (50.395) | 11.11 (19.245) | -6.67 (43.885) |
| Emotional Functioning | -5.95 (14.203) | -2.78 (4.811) | -5.0 (11.915) |
| Cognitive Functioning | -7.14 (21.207) | 0.0 (0.0) | -5.0 (17.656) |
| Social Functioning | -14.29 (33.923) | 5.56 (19.245) | -8.33 (30.682) |
| Fatigue | 12.7 (31.706) | -14.81 (12.83) | 4.44 (29.722) |
| Nausea and Vomiting | 0.0 (0.0) | 0.0 (0.0) | 0.0 (0.0) |
| Pain | 2.38 (37.796) | -27.78 (25.459) | -6.67 (36.175) |
| Dyspnoea | 0.0 (0.0) | -11.11 (19.245) | -3.33 (10.541) |
| Insomnia | 14.29 (17.817) | -22.22 (19.245) | 3.33 (24.595) |
| Appetite Loss | 0.0 (19.245) | 22.22 (19.245) | 6.67 (21.082) |
| Constipation | 14.29 (17.817) | 0.0 (0.0) | 10.0 (16.102) |
| Diarrhea | -4.76 (12.599) | -11.11 (19.245) | -6.67 (14.055) |
| Financial Difficulties | 4.76 (23.002) | 0.0 (33.333) | 3.33 (24.595) |
The PRO analysis set included all participants in the safety analysis set who completed a baseline and at least one postbaseline PRO assessment. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Myeloma-Specific Module (EORTC QLQ-MY20) at Cycle 9 Day 1
Units on a scale · Standard Deviation · 时间窗: Baseline (prior to the date of the first dose of study intervention), and Cycle 9 Day 1
| 分类 | Phase 2 （n=7） | Phase 1b （n=3） | Phase 1b + Phase 2 （n=10） |
|---|---|---|---|
| Body Image | -19.05 (37.796) | 11.11 (19.245) | -10.0 (35.312) |
| Future Perspective | -11.11 (15.713) | 0.0 (22.222) | -7.78 (17.411) |
| Disease Symptoms | -1.59 (18.346) | -5.56 (11.111) | -2.78 (15.984) |
| Side Effects of Treatment | 2.28 (9.683) | -7.78 (13.461) | -0.74 (11.241) |
The PRO analysis set included all participants in the safety analysis set who completed a baseline and at least one postbaseline PRO assessment. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Chemotherapy-Induced Peripheral Neuropathy (EORTC QLQ CIPN20) at Cycle 9 Day 1
Units on a scale · Standard Deviation · 时间窗: Baseline (prior to the date of the first dose of study intervention), and Cycle 9 Day 1
| 分类 | Phase 2 （n=7） | Phase 1b （n=3） | Phase 1b + Phase 2 （n=10） |
|---|---|---|---|
| Sensory Subscale | 3.17 (10.127) | 0.0 (0.0) | 2.22 (8.41) |
| Motor Subscale | 10.71 (25.057) | -7.54 (7.176) | 5.24 (22.533) |
| Autonomic Subscale | 3.97 (6.964) | -16.67 (5.556) | -2.22 (11.771) |
The PRO analysis set included all participants in the safety analysis set who completed a baseline and at least one postbaseline PRO assessment. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
Change From Baseline in EuroQol Five Dimensions Questionnaire (EQ-5D) Index Score and in EQ-5D Visual Analogue Score (EQ-VAS) at Cycle 9 Day 1
Units on a scale · Standard Deviation · 时间窗: Baseline (prior to the date of the first dose of study intervention), and Cycle 9 Day 1
| 分类 | Phase 2 （n=7） | Phase 1b （n=3） | Phase 1b + Phase 2 （n=10） |
|---|---|---|---|
| EQ-5D Index Score | -0.06 (0.252) | 0.13 (0.207) | -0.01 (0.246) |
| EQ-VAS | -5 (7.07) | 6 (5.29) | -1.7 (8.23) |
The PRO analysis set included all participants in the safety analysis set who completed a baseline and at least one postbaseline PRO assessment. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
安全性
| 组别 | 严重不良事件 | 死亡 |
|---|---|---|
| Phase 2 | 22 / 30 | 17 / 30 |
| Phase 1b | 6 / 8 | 6 / 8 |
| Phase 1b + Phase 2 | 28 / 38 | 23 / 38 |
最常见的严重不良事件（人数）
| 事件 | Phase 2 | Phase 1b | Phase 1b + Phase 2 |
|---|---|---|---|
| Pneumonia | 12 / 30 | 3 / 8 | 15 / 38 |
| COVID-19 | 2 / 30 | 1 / 8 | 3 / 38 |
| Death | 2 / 30 | 0 / 8 | 2 / 38 |
| Cytokine release syndrome | 1 / 30 | 1 / 8 | 2 / 38 |
| COVID-19 pneumonia | 2 / 30 | 0 / 8 | 2 / 38 |
| Plasma cell myeloma | 1 / 30 | 1 / 8 | 2 / 38 |
| Respiratory failure | 2 / 30 | 0 / 8 | 2 / 38 |
| Anaemia | 0 / 30 | 1 / 8 | 1 / 38 |
| Coagulopathy | 0 / 30 | 1 / 8 | 1 / 38 |
| Neutropenia | 0 / 30 | 1 / 8 | 1 / 38 |
数值为申办方在 ClinicalTrials.gov 公示的原始数据，未经重新计算；括号内为公示的离散度（如 95% 置信区间）。
研究者
研究点 (15)
标识符
- NCT 编号
- NCT05228470
- 其他研究编号
- C1071008, NCT05228470
日期
- 首次提交
- (4年前)
- 首次发布
- (4年前)
- 主要完成日期
- (3年前)
- 研究完成日期
- (去年)
- 最近核实
- (29天前)
- 最近更新
- (昨天)
监管与共享
- FDA 监管药物
- 是
- FDA 监管器械
- 否
- 个体参与者数据共享计划
- 是
- 是否有结果
- 是
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.