A Phase 1 Study of SEA-BCMA in Patients With Relapsed or Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Seagen Inc.
- 入组人数
- 83
- 试验地点
- 13
- 主要终点
- Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), Treatment Related TEAEs and Greater Than or Equal to (>=) Grade 3 TEAEs: Part A
研究概览
简要总结
This trial will study SEA-BCMA to find out whether it is an effective treatment for multiple myeloma (MM) and what side effects (unwanted effects) may occur.
The study will have several parts. In Parts A and B, participants get SEA-BCMA by itself. This part of the study will find out how much SEA-BCMA should be given for treatment and how often. It will also find out how safe the treatment is and how well it works.
In Part C of the study, participants will get SEA-BCMA and dexamethasone. In Part D, participants will get SEA-BCMA, dexamethasone, and pomalidomide. Dexamethasone and pomalidomide are both drugs that can be used to treat multiple myeloma. These parts of the study will find out whether these drugs are safe when used together.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Histologically confirmed diagnosis of MM
- •Must have MM that is relapsed or refractory
- •Has received a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody
- •Measurable disease, as defined by at least one of the following: (1) serum M protein 0.5 g/dL or higher, (2) urine M protein 200 mg/24 hour or higher, and (3) serum immunoglobulin free light chain (FLC) 10 mg/dL or higher and abnormal serum immunoglobulin kappa lambda FLC ratio.
- •Eastern Cooperative Oncology Group (ECOG) status score of 0 or 1
- •Life expectancy of greater than 3 months in the opinion of the investigator
- •Adequate hematologic, renal, and hepatic function
排除标准
- •Parts A and D: Prior treatment with a BCMA-directed therapy
- •History of another malignancy within 3 years
- •Active cerebral or meningeal disease related to the underlying malignancy
- •Uncontrolled Grade 3 or higher infection
- •Prior antitumor therapy that is not completed at least 4 weeks prior to first dose of study drug, or at least 2 weeks if progressing. Prior CAR-T-cell therapy must be completed 8 weeks before first dose of study drug.
- •Combination therapy only:
- •Known intolerance to corticosteroids
- •Uncontrolled psychoses
研究组 & 干预措施
Part D: SEA-BCMA + Pomalidomide + Dexamethasone Combination Therapy
SEA-BCMA + dexamethasone + pomalidomide
干预措施: pomalidomide (Drug)
Parts A and B: SEA-BCMA Monotherapy
SEA-BCMA
干预措施: SEA-BCMA (Drug)
Part C: SEA-BCMA + Dexamethasone Combination Therapy
SEA-BCMA + dexamethasone
干预措施: SEA-BCMA (Drug)
Part C: SEA-BCMA + Dexamethasone Combination Therapy
SEA-BCMA + dexamethasone
干预措施: dexamethasone (Drug)
Part D: SEA-BCMA + Pomalidomide + Dexamethasone Combination Therapy
SEA-BCMA + dexamethasone + pomalidomide
干预措施: SEA-BCMA (Drug)
Part D: SEA-BCMA + Pomalidomide + Dexamethasone Combination Therapy
SEA-BCMA + dexamethasone + pomalidomide
干预措施: dexamethasone (Drug)
结局指标
主要结局
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), Treatment Related TEAEs and Greater Than or Equal to (>=) Grade 3 TEAEs: Part A
时间窗: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment up to 44 months (maximum follow up of 45 months)
An adverse event (AE) was any untoward medical occurrence in a participant/ clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. TEAEs were defined as newly occurring (not present at baseline)/worsening after first dose of investigational product (IP). TESAEs were any untoward medical occurrence at any dose that: suspected to cause death; life-threatening; required hospitalization; persistent/significant disability/incapacity \& may cause congenital anomaly/birth defect. Treatment related TEAEs were related to study treatment and relatedness was judged by investigator. TEAEs were graded according to National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v) 4.03 (grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening).
Number of Participants With TEAEs, TESAEs, Treatment Related TEAEs and >=Grade 3 TEAEs: Part B
时间窗: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment up to 33 months (maximum follow up of 34 months)
An AE was any untoward medical occurrence in a participant/ clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. TEAEs were defined as newly occurring (not present at baseline)/worsening after first dose of IP. TESAEs were any untoward medical occurrence at any dose that: suspected to cause death; life-threatening; required hospitalization; persistent/significant disability/incapacity \& may cause congenital anomaly/birth defect. Treatment related TEAEs were related to study treatment and relatedness was judged by investigator. TEAEs were graded according to NCI CTCAE v 4.03 (grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening).
Number of Participants With TEAEs, TESAEs, Treatment Related TEAEs and >=Grade 3 TEAEs: Part C
时间窗: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment up to 36 months (maximum follow up of 37 months)
An AE was any untoward medical occurrence in a participant/ clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. TEAEs were defined as newly occurring (not present at baseline)/worsening after first dose of IP. TESAEs were any untoward medical occurrence at any dose that: suspected to cause death; life-threatening; required hospitalization; persistent/significant disability/incapacity \& may cause congenital anomaly/birth defect. Treatment related TEAEs were related to study treatment and relatedness was judged by investigator. TEAEs were graded according to NCI CTCAE v 4.03 (grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening).
Number of Participants With TEAEs, TESAEs, Treatment Related TEAEs and >=Grade 3 TEAEs: Part D
时间窗: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment up to 19 months (maximum follow up of 20 months)
An AE was any untoward medical occurrence in a participant/ clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. TEAEs were defined as newly occurring (not present at baseline)/worsening after first dose of IP. TESAEs were any untoward medical occurrence at any dose that: suspected to cause death; life-threatening; required hospitalization; persistent/significant disability/incapacity \& may cause congenital anomaly/birth defect. Treatment related TEAEs were related to study treatment and relatedness was judged by investigator. TEAEs were graded according to NCI CTCAE v 4.03 (grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening).
Number of Participants With Maximum Laboratory Toxicity Grade, by NCI-CTCAE v4.03- Serum Chemistry: Part A
时间窗: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment up to 44 months (maximum follow up of 45 months)
The following serum chemistry laboratory parameters were assessed: Alanine aminotransferase high, albumin low, alkaline phosphatase high, amylase high, aspartate aminotransferase high, calcium corrected for albumin high, calcium corrected for albumin low, creatinine high, glucose high, glucose low, lipase high, phosphate low, potassium high, potassium low, sodium high, sodium low, total bilirubin high and urate high. Chemistry laboratory parameters abnormalities were graded according to NCI CTCAE v 4.03 (grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening). Participants with any serum chemistry parameter meeting CTCAE grade 1 to 4 were reported.
Number of Participants With Maximum Laboratory Toxicity Grade, by NCI-CTCAE v4.03- Serum Chemistry: Part B
时间窗: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment up to 33 months (maximum follow up of 34 months)
The following serum chemistry laboratory parameters were assessed: Alanine aminotransferase high, albumin low, alkaline phosphatase high, amylase high, aspartate aminotransferase high, calcium corrected for albumin high, calcium corrected for albumin low, creatinine high, glucose high, glucose low, lipase high, phosphate low, potassium high, potassium low, sodium high, sodium low, total bilirubin high and urate high. Chemistry laboratory parameters abnormalities were graded according to NCI CTCAE v 4.03 (grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening). Participants with any serum chemistry parameter meeting CTCAE grade 1 to 4 were reported.
Number of Participants With Maximum Laboratory Toxicity Grade, by NCI-CTCAE v4.03- Serum Chemistry: Part C
时间窗: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment up to 36 months (maximum follow up of 37 months)
The following serum chemistry laboratory parameters were assessed: Alanine aminotransferase high, albumin low, alkaline phosphatase high, amylase high, aspartate aminotransferase high, calcium corrected for albumin high, calcium corrected for albumin low, creatinine high, glucose high, glucose low, lipase high, phosphate low, potassium high, potassium low, sodium high, sodium low, total bilirubin high and urate high. Chemistry laboratory parameters abnormalities were graded according to NCI CTCAE v 4.03 (grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening). Participants with any serum chemistry parameter meeting CTCAE grade 1 to 4 were reported.
Number of Participants With Maximum Laboratory Toxicity Grade, by NCI-CTCAE v4.03- Serum Chemistry: Part D
时间窗: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment up to 19 months (maximum follow up of 20 months)
The following serum chemistry laboratory parameters were assessed: Alanine aminotransferase high, albumin low, alkaline phosphatase high, amylase high, aspartate aminotransferase high, calcium corrected for albumin high, calcium corrected for albumin low, creatinine high, glucose high, glucose low, lipase high, phosphate low, potassium high, potassium low, sodium high, sodium low, total bilirubin high and urate high. Chemistry laboratory parameters abnormalities were graded according to NCI CTCAE v 4.03 (grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening). Participants with any serum chemistry parameter meeting CTCAE grade 1 to 4 were reported.
Number of Participants With Maximum Laboratory Toxicity Grade, by NCI-CTCAE v4.03- Hematology: Part A
时间窗: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment up to 44 months (maximum follow up of 45 months)
The following hematology laboratory parameters were assessed: hemoglobin high, hemoglobin low, leukocytes high, leukocytes low, lymphocytes high, lymphocytes low, neutrophils low and platelets low. Laboratory abnormality events were graded according to NCI CTCAE v 4.03 (grade 1=mild, grade 2=moderate, grade 3= severe and grade 4= life-threatening). Participants with any hematology parameter meeting CTCAE grade 1 to 4 were reported.
Number of Participants With Maximum Laboratory Toxicity Grade, by NCI-CTCAE v4.03- Hematology: Part B
时间窗: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment up to 33 months (maximum follow up of 34 months)
The following hematology laboratory parameters were assessed: hemoglobin high, hemoglobin low, leukocytes high, leukocytes low, lymphocytes high, lymphocytes low, neutrophils low and platelets low. Laboratory abnormality events were graded according to NCI CTCAE v 4.03 (grade 1=mild, grade 2=moderate, grade 3= severe and grade 4= life-threatening). Participants with any hematology parameter meeting CTCAE grade 1 to 4 were reported.
Number of Participants With Maximum Laboratory Toxicity Grade, by NCI-CTCAE v4.03- Hematology: Part C
时间窗: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment up to 36 months (maximum follow up of 37 months)
The following hematology laboratory parameters were assessed: hemoglobin high, hemoglobin low, leukocytes high, leukocytes low, lymphocytes high, lymphocytes low, neutrophils low and platelets low. Laboratory abnormality events were graded according to NCI CTCAE v 4.03 (grade 1=mild, grade 2=moderate, grade 3= severe and grade 4= life-threatening). Participants with any hematology parameter meeting CTCAE grade 1 to 4 were reported.
Number of Participants With Maximum Laboratory Toxicity Grade, by NCI-CTCAE v4.03- Hematology: Part D
时间窗: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment up to 19 months (maximum follow up of 20 months)
The following hematology laboratory parameters were assessed: hemoglobin high, hemoglobin low, leukocytes high, leukocytes low, lymphocytes high, lymphocytes low, neutrophils low and platelets low. Laboratory abnormality events were graded according to NCI CTCAE v 4.03 (grade 1=mild, grade 2=moderate, grade 3= severe and grade 4= life-threatening). Participants with any hematology parameter meeting CTCAE grade 1 to 4 were reported.
Number of Participants With Dose Limiting Toxicities (DLTs): Part A
时间窗: Cycle 1 (28 days)
The DLT-evaluation period was the first cycle of treatment. DLTs were graded according to the NCI-CTCAE, v 4.03, and were defined as any of the following events during the DLT-evaluation period: a ) A delay of SEA-BCMA treatment by more than 7 days due to toxicity, b) Any AE \>=Grade 3, unless deemed by the safety monitoring committee (SMC) to be clearly unrelated to SEA-BCMA except for the AEs as pre specified in protocol to be considered a DLT and c) Any treatment related death.
Number of Participants With DLTs: Part B
时间窗: Cycle 1 (28 days)
The DLT-evaluation period was the first cycle of treatment. DLTs were graded according to the NCI-CTCAE, v 4.03, and were defined as any of the following events during the DLT-evaluation period: a ) A delay of SEA-BCMA treatment by more than 7 days due to toxicity, b) Any AE \>=Grade 3, unless deemed by the SMC to be clearly unrelated to SEA-BCMA except for the AEs as pre specified in protocol to be considered a DLT and c) Any treatment related death.
Number of Participants With DLTs: Part C
时间窗: Cycle 1 (28 days)
The DLT-evaluation period was the first cycle of treatment. DLTs were graded according to the NCI-CTCAE, v 4.03, and were defined as any of the following events during the DLT-evaluation period: a ) A delay of SEA-BCMA treatment by more than 7 days due to toxicity, b) Any AE \>=Grade 3, unless deemed by the SMC to be clearly unrelated to SEA-BCMA except for the AEs as pre specified in protocol to be considered a DLT and c) Any treatment related death.
Number of Participants With DLTs: Part D
时间窗: Cycle 1 (28 days)
The DLT-evaluation period was the first cycle of treatment. DLTs were graded according to the NCI-CTCAE, v 4.03, and were defined as any of the following events during the DLT-evaluation period: a ) A delay of SEA-BCMA treatment by more than 7 days due to toxicity, b) Any AE \>=Grade 3, unless deemed by the SMC to be clearly unrelated to SEA-BCMA except for the AEs as pre specified in protocol to be considered a DLT and c) Any treatment related death.
次要结局
- Area Under the Serum Concentration-Time Curve From Time 0 to Day 14 (AUC0-14) of SEA-BCMA: Part A(Cycle 1 and 2: Pre dose, 1 and 2 hour intradose, end of drug administration, 2, 6 , 24, 72, 168 and 336 hours post end of infusion on Day 1)
- Area Under the Serum Concentration-Time Curve From Time 0 to Day 7 (AUC0-7) of SEA-BCMA: Part A(Cycle 1: Pre dose, 1 and 2 hour intradose, end of drug administration, 2, 6 , 24, 72, and 168 hours post end of infusion on Day 1)
- AUC0-7 of SEA-BCMA: Part B(Cycle 1: Pre dose, 1 and 2 hour intradose, end of drug administration, 2, 6 , 24, 72, and 168 hours post end of infusion on Day 1)
- AUC0-7 of SEA-BCMA: Part C(Cycle 1: Pre dose, 1 and 2 hour intradose, end of drug administration, 2, 6 , 24, 72, and 168 hours post end of infusion on Day 1)
- AUC0-7 of SEA-BCMA: Part D(Cycle 1: Pre dose, 1 and 2 hour intradose, end of drug administration, 2, 6 , 24, 72, and 168 hours post end of infusion on Day 1)
- Maximum Observed Serum Concentration (Cmax) of SEA-BCMA: Part A(Cycle 1 and 2: Pre dose, 1 and 2 hour intradose, end of drug administration, 2, 6 , 24, 72, 168 and 336 hours post end of infusion on Day 1 and 15)
- Cmax of SEA-BCMA: Part B(Cycle 1: Pre dose, 1 and 2 hour intradose, end of drug administration, 2, 6 , 24, 72, 168 and 336 hours post end of infusion on Day 1 and 15)
- Cmax of SEA-BCMA: Part C(Cycle 1: Pre dose, 1 and 2 hour intradose, end of drug administration, 2, 6 , 24, 72, 168 and 336 hours post end of infusion on Day 1 and 15)
- Cmax of SEA-BCMA: Part D(Cycle 1:Pre dose, 1 and 2 hour intradose, end of drug administration, 2, 6 , 24, 72, 168 and 336 hours post end of infusion on Day 1 and 15)
- Number of Participants With SEA-BCMA Antitherapeutic Antibodies (ATA): Part A(Anytime during study (maximum up to 45 months))
- Number of Participants With SEA-BCMA, ATA: Part B(Anytime during study (maximum up to 34 months))
- Number of Participants With SEA-BCMA, ATA: Part C(Anytime during study (maximum up to 37 months))
- Number of Participants With SEA-BCMA, ATA: Part D(Anytime during study (maximum up to 20 months))
- Objective Response Rate (ORR) as Per the International Myeloma Working Group (IMWG) Uniform Response Criteria: Part A(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 45 months))
- ORR as Per the IMWG Uniform Response Criteria: Part B(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 months))
- ORR as Per the IMWG Uniform Response Criteria: Part C(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 37 months))
- ORR as Per the IMWG Uniform Response Criteria: Part D(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 20 months))
- Percentage of Participants With Best Overall Response (BOR) as Per the IMWG Uniform Response Criteria: Part A(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 45 months))
- Percentage of Participants With BOR as Per the IMWG Uniform Response Criteria: Part B(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 months))
- Percentage of Participants With BOR as Per the IMWG Uniform Response Criteria: Part C(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 37 months))
- Percentage of Participants With BOR as Per the IMWG Uniform Response Criteria: Part D(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 20 months))
- Duration of Objective Response (DOR) as Per the IMWG Uniform Response Criteria: Part A(From the first dose of study treatment until the first documented OR (sCR or CR or PR or VGPR) on or before the first documented PD or death or censoring date, whichever occurred first (maximum up to 45 months))
- DOR as Per the IMWG Uniform Response Criteria: Part B(From the first dose of study treatment until the first documented OR (sCR or CR or PR or VGPR) on or before the first documented PD or death or censoring date, whichever occurred first (maximum up to 34 months))
- DOR as Per the IMWG Uniform Response Criteria: Part C(From the first dose of study treatment until the first documented OR (sCR or CR or PR or VGPR) on or before the first documented PD or death or censoring date, whichever occurred first (maximum up to 37 months))
- DOR as Per the IMWG Uniform Response Criteria: Part D(From the first dose of study treatment until the first documented OR (sCR or CR or PR or VGPR) on or before the first documented PD or death or censoring date, whichever occurred first (maximum up to 20 months))
- Progression Free Survival (PFS): Part A(From the date of first dose until the first documentation of PD or death or censoring date, whichever occurred first (maximum up to 45 months))
- PFS: Part B(From the date of first dose until the first documentation of PD or death or censoring date, whichever occurred first (maximum up to 34 months))
- PFS: Part C(From the date of first dose until the first documentation of PD or death or censoring date, whichever occurred first (maximum up to 37 months))
- PFS: Part D(From the date of first dose until the first documentation of PD or death or censoring date, whichever occurred first (maximum up to 20 months))
- Overall Survival (OS): Part A(From date of start of study treatment until date of death or censoring date (maximum up to 45 months))
- OS: Part B(From date of start of study treatment until date of death or censoring date (maximum up to 34 months))
- OS: Part C(From date of start of study treatment until date of death or censoring date (maximum up to 37 months))
- OS: Part D(From date of start of study treatment until date of death or censoring date (maximum up to 20 months))