A Safety Study of SEA-BCMA in Patients With Multiple Myeloma

A Phase 1 Study of SEA-BCMA in Patients With Relapsed or Refractory Multiple Myeloma

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.

Study Overview

• Status: Terminated
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: pomalidomide; Drug: SEA-BCMA; Drug: dexamethasone

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University School of Medicine
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Rocky Mountain Cancer Centers - Aurora
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Holden Comprehensive Cancer Center / University of Iowa
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas Cancer Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University in St Louis
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medicine
    • Rochester, New York, United States, 14642
      • James P. Wilmot Cancer Center / University of Rochester Medical Center
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Willamette Valley Cancer Institute and Research Center
  • Texas
    • Austin, Texas, United States, 78705
      • Texas Oncology - Austin Midtown
    • Tyler, Texas, United States, 75702
      • Texas Oncology - Northeast Texas
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists, PC
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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:

  1. Known intolerance to corticosteroids
  2. Uncontrolled psychoses

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Parts A and B: SEA-BCMA Monotherapy; SEA-BCMA	Drug: SEA-BCMA; Given into the vein (IV; intravenously)
Experimental: Part C: SEA-BCMA + Dexamethasone Combination Therapy; SEA-BCMA + dexamethasone	Drug: SEA-BCMA; Given into the vein (IV; intravenously); Drug: dexamethasone; Given by mouth (orally) or by IV
Experimental: Part D: SEA-BCMA + Pomalidomide + Dexamethasone Combination Therapy; SEA-BCMA + dexamethasone + pomalidomide	Drug: pomalidomide; Given orally; Drug: SEA-BCMA; Given into the vein (IV; intravenously); Drug: dexamethasone; Given by mouth (orally) or by IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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).	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)
Number of Participants With TEAEs, TESAEs, Treatment Related TEAEs and >=Grade 3 TEAEs: Part B	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).	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)
Number of Participants With TEAEs, TESAEs, Treatment Related TEAEs and >=Grade 3 TEAEs: Part C	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).	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)
Number of Participants With TEAEs, TESAEs, Treatment Related TEAEs and >=Grade 3 TEAEs: Part D	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).	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)
Number of Participants With Maximum Laboratory Toxicity Grade, by NCI-CTCAE v4.03- Serum Chemistry: Part A	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.	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)
Number of Participants With Maximum Laboratory Toxicity Grade, by NCI-CTCAE v4.03- Serum Chemistry: Part B	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.	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)
Number of Participants With Maximum Laboratory Toxicity Grade, by NCI-CTCAE v4.03- Serum Chemistry: Part C	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.	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)
Number of Participants With Maximum Laboratory Toxicity Grade, by NCI-CTCAE v4.03- Serum Chemistry: Part D	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.	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)
Number of Participants With Maximum Laboratory Toxicity Grade, by NCI-CTCAE v4.03- Hematology: Part A	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.	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)
Number of Participants With Maximum Laboratory Toxicity Grade, by NCI-CTCAE v4.03- Hematology: Part B	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.	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)
Number of Participants With Maximum Laboratory Toxicity Grade, by NCI-CTCAE v4.03- Hematology: Part C	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.	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)
Number of Participants With Maximum Laboratory Toxicity Grade, by NCI-CTCAE v4.03- Hematology: Part D	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.	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)
Number of Participants With Dose Limiting Toxicities (DLTs): Part A	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.	Cycle 1 (28 days)
Number of Participants With DLTs: Part B	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.	Cycle 1 (28 days)
Number of Participants With DLTs: Part C	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.	Cycle 1 (28 days)
Number of Participants With DLTs: Part D	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.	Cycle 1 (28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Serum Concentration-Time Curve From Time 0 to Day 14 (AUC0-14) of SEA-BCMA: Part A	Area under the observed concentration-time curve from the time of dosing to Day 14 calculated by log-linear trapezoidal approximation.	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	Area under the observed concentration-time curve from the time of dosing to Day 7 calculated by log-linear trapezoidal approximation.	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	Area under the observed concentration-time curve from the time of dosing to Day 7 calculated by log-linear trapezoidal approximation.	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	Area under the observed concentration-time curve from the time of dosing to Day 7 calculated by log-linear trapezoidal approximation.	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	Area under the observed concentration-time curve from the time of dosing to Day 7 calculated by log-linear trapezoidal approximation.	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	A positive baseline ATA result was considered positive post-baseline if the post-baseline ATA titer result was at least four times higher than the baseline result.	Anytime during study (maximum up to 45 months)
Number of Participants With SEA-BCMA, ATA: Part B	A positive baseline ATA result was considered positive post-baseline if the post-baseline ATA titer result was at least four times higher than the baseline result.	Anytime during study (maximum up to 34 months)
Number of Participants With SEA-BCMA, ATA: Part C	A positive baseline ATA result was considered positive post-baseline if the post-baseline ATA titer result was at least four times higher than the baseline result.	Anytime during study (maximum up to 37 months)
Number of Participants With SEA-BCMA, ATA: Part D	A positive baseline ATA result was considered positive post-baseline if the post-baseline ATA titer result was at least four times higher than the baseline result.	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	ORR: Percentage of participants with an objective response (OR) per investigator. Participant was determined to have an OR if, based on 2016 IMWG uniform response criteria, & achieved stringent complete response (sCR), Complete response (CR), very good partial response(VGPR) & partial response(PR): free light chain(FLC) ratio & absence of clonal cells in bone marrow by immunohistochemistry(IC)/ immunofluorescence(IF). CR: negative immunofixation of serum & urine, disappearance of any soft tissue plasmacytomas(STP), 5% plasma cells in bone marrow. VGPR: serum & urine M-protein (UMP) detectable by immunofixation but not on electrophoresis/ >= 90% reduction in serum M-protein (SMP) level+UMP level <100 mg/24 hr, PR: >=50% reduction of SMP & reduction in 24-hr urinary M-protein by >=90%/to <200 mg/24 hr. If SMP & UMP are unmeasurable, a ≥50% decrease in the difference between involved & uninvolved FLC levels were required in place of the M-protein 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 45 months)
ORR as Per the IMWG Uniform Response Criteria: Part B	The ORR was defined as the percentage of participants with an OR per investigator. A participant was determined to have an OR if, based on the 2016 IMWG uniform response criteria, and achieved a sCR, CR, VGPR, or a PR. sCR: FLC ratio & absence of clonal cells in bone marrow by IC/IF. CR: negative immunofixation of serum & urine, disappearance of any STP, 5% plasma cells in bone marrow. VGPR: serum and UMP detectable by immunofixation but not on electrophoresis or >= 90% reduction in SMP level+UMP level <100 mg/24 hour, PR: >=50% reduction of SMP & reduction in 24-hour urinary M-protein by >=90%/to <200 mg/24 hour. If SMP & UMP are unmeasurable, a ≥50% decrease in the difference between involved & uninvolved FLC levels were required in place of the M-protein criteria. In addition to above criteria, if present at baseline, >=50% reduction in the size of STP were also required.	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	The ORR was defined as the percentage of participants with an OR per investigator. A participant was determined to have an OR if, based on the 2016 IMWG uniform response criteria, and achieved a sCR, CR, VGPR, or a PR. sCR: FLC ratio & absence of clonal cells in bone marrow by IC/IF. CR: negative immunofixation of serum & urine, disappearance of any STP, 5% plasma cells in bone marrow. VGPR: serum and UMP detectable by immunofixation but not on electrophoresis or >= 90% reduction in SMP level+UMP level <100 mg/24 hour, PR: >=50% reduction of SMP & reduction in 24-hour urinary M-protein by >=90%/to <200 mg/24 hour. If SMP & UMP are unmeasurable, a ≥50% decrease in the difference between involved & uninvolved FLC levels were required in place of the M-protein criteria. In addition to above criteria, if present at baseline, >=50% reduction in the size of STP were also required.	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	The ORR was defined as the percentage of participants with an OR per investigator. A participant was determined to have an OR if, based on the 2016 IMWG uniform response criteria, and achieved a sCR, CR, VGPR, or a PR. sCR: FLC ratio & absence of clonal cells in bone marrow by IC/IF. CR: negative immunofixation of serum & urine, disappearance of any STP, 5% plasma cells in bone marrow. VGPR: serum and UMP detectable by immunofixation but not on electrophoresis/ >= 90% reduction in SMP level+UMP level <100 mg/24 hour, PR: >=50% reduction of SMP & reduction in 24-hour urinary M-protein by >=90%/to <200 mg/24 hour. If SMP & UMP are unmeasurable, a ≥50% decrease in the difference between involved & uninvolved FLC levels were required in place of the M-protein criteria. In addition to above criteria, if present at baseline, >=50% reduction in the size of STP were also required.	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	BOR consisted of MRD-negative CR,sCR,CR,VGPR,PR,MR,SD & PD per 2016 IMWG. MRD: evaluated using adaptive next generation sequencing(NGS) for MRD assay & carried out on relevant specimen to understand activity of SEA-BCMA. sCR: CR & normal FLC ratio & absence of clonal cells in bone marrow by IC/ IF. CR: Negative immunofixation of serum & urine disappearance of any STP, & <5% plasma cells in bone marrow. VGPR: SMP & UMP detectable by IF but not on electrophoresis/ >= 90% reduction(R) in SMP level+UMP level <100 mg/24 hr, PR: >=50% R of SMP & R in 24-hr UMP by >=90%/by <200 mg/24 hr. If SMP & UMP are unmeasurable, >=50% decrease in difference between involved & uninvolved FLC levels were required in place of M-protein criteria. SD: Not meeting criteria for CR, VGPR, PR, MR, or progression. MR: 25-49% R of SMP & R in 24-hr UMP by 50-89%, which still exceeds 200mg/24 hr. DP: objective evidence of tumor progression(based on serum/urine/BM assessments) &/clinical progression/investigator.	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	BOR consisted of MRD-negative CR, sCR, CR, VGPR, PR, MR, SD & PD per 2016 IMWG. MRD: evaluated using adaptive NGS for MRD assay & carried out on relevant specimen to understand activity of SEA-BCMA. sCR: CR & normal FLC ratio & absence of clonal cells in bone marrow by IC/ IF. CR: Negative immunofixation of serum & urine disappearance of any STP, & <5% plasma cells in bone marrow. VGPR: SMP & UMP detectable by IF but not on electrophoresis/ >= 90% reduction(R) in SMP level+UMP level <100 mg/24 hr, PR: >=50% R of SMP & R in 24-hr UMP by >=90%/by <200 mg/24 hr. If SMP & UMP are unmeasurable, >=50% decrease in difference between involved & uninvolved FLC levels were required in place of M-protein criteria. SD: Not meeting criteria for CR, VGPR, PR, MR, or progression. MR: 25-49% R of SMP & R in 24-hr UMP by 50-89%, which still exceeds 200mg/24 hr. DP: objective evidence of tumor progression(based on serum/urine/BM assessments) &/clinical progression/investigator.	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	BOR consisted of MRD-negative CR, sCR, CR, VGPR, PR, MR, SD & PD per 2016 IMWG. MRD: evaluated using NGS for MRD assay & carried out on relevant specimen to understand activity of SEA-BCMA. sCR: CR & normal FLC ratio & absence of clonal cells in bone marrow by IC/ IF. CR: Negative immunofixation of serum & urine disappearance of any STP, & <5% plasma cells in bone marrow. VGPR: SMP & UMP detectable by IF but not on electrophoresis/ >= 90% reduction(R) in SMP level+UMP level <100 mg/24 hr, PR: >=50% R of SMP & R in 24-hr UMP by >=90%/by <200 mg/24 hr. If SMP & UMP are unmeasurable, >=50% decrease in difference between involved & uninvolved FLC levels were required in place of M-protein criteria. SD: Not meeting criteria for CR, VGPR, PR, MR, or progression. MR: 25-49% R of SMP & R in 24-hr UMP by 50-89%, which still exceeds 200mg/24 hr. DP: objective evidence of tumor progression(based on serum/urine/BM assessments) &/clinical progression/investigator.	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	BOR consisted of MRD-negative CR,sCR,CR,VGPR,PR,MR,SD & PD per 2016 IMWG. MRD: evaluated using adaptive NGS for MRD assay & carried out on relevant specimen to understand activity of SEA-BCMA. sCR: CR & normal FLC ratio & absence of clonal cells in bone marrow by IC/ IF. CR: Negative immunofixation of serum & urine disappearance of any STP, & <5% plasma cells in bone marrow. VGPR: SMP & UMP detectable by IF but not on electrophoresis/ >= 90% reduction(R) in SMP level+UMP level <100 mg/24 hr, PR: >=50% R of SMP & R in 24-hr UMP by >=90%/by <200 mg/24 hr. If SMP & UMP are unmeasurable, >=50% decrease in difference between involved & uninvolved FLC levels were required in place of M-protein criteria. SD: Not meeting criteria for CR, VGPR, PR, MR, or progression. MR: 25-49% R of SMP & R in 24-hr UMP by 50-89%, which still exceeds 200mg/24 hr. DP: objective evidence of tumor progression(based on serum/urine/BM assessments) &/clinical progression/investigator.	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	DOR: Time from first documentation of OR(sCR,CR,VGPR/PR) to first documentation of PD/death due to any cause, whichever came first. PD: Objective evidence of tumor progression(TP) (based on serum, urine/BM assessments) &/clinical progression/ investigator. sCR: CR, normal FLC ratio & absence of clonal cells in bone marrow by IC/IF. CR: Negative immunofixation of serum&urine, disappearance of any STP, &<5% plasma cells in bone marrow. VGPR: Serum & UMP detectable by immunofixation but not on electrophoresis/ >= 90% reduction(R) in SMP level+UMP level <100 mg/24 hour, PR: >=50%R of SMP & R in 24-hour UMP by >=90% or to <200 mg/24 hour. DOR: censored on date of last disease assessment documenting absence of PD for participants who do not have PD & were still on study at the time of an analysis/removed from study prior to documentation of TP. Participants started new antitumor treatment prior to documentation of PD were censored at last disease assessment prior to start of new treatment.	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	DOR: Time from first documentation of OR(sCR,CR,VGPR/PR) to first documentation of PD/death due to any cause, whichever came first. PD: Objective evidence of tumor progression(TP) (based on serum, urine/BM assessments) &/clinical progression/ investigator. sCR: CR, normal FLC ratio & absence of clonal cells in bone marrow by IC/IF. CR: Negative immunofixation of serum&urine, disappearance of any STP, &<5% plasma cells in bone marrow. VGPR: Serum & UMP detectable by immunofixation but not on electrophoresis/ >= 90% reduction(R) in SMP level+UMP level <100 mg/24 hour, PR: >=50%R of SMP & R in 24-hour UMP by >=90% or to <200 mg/24 hour. DOR: censored on date of last disease assessment documenting absence of PD for participants who do not have PD & were still on study at the time of an analysis/removed from study prior to documentation of TP. Participants started new antitumor treatment prior to documentation of PD were censored at last disease assessment prior to start of new treatment.	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	DOR: Time from first documentation of OR(sCR,CR,VGPR/PR) to first documentation of PD/death due to any cause, whichever came first. PD: Objective evidence of tumor progression(TP) (based on serum, urine/BM assessments) &/clinical progression/ investigator. sCR: CR, normal FLC ratio & absence of clonal cells in bone marrow by IC/IF. CR: Negative immunofixation of serum&urine, disappearance of any STP, &<5% plasma cells in bone marrow. VGPR: Serum & UMP detectable by immunofixation but not on electrophoresis/ >= 90% reduction(R) in SMP level+UMP level <100 mg/24 hour, PR: >=50%R of SMP & R in 24-hour UMP by >=90% or to <200 mg/24 hour. DOR: censored on date of last disease assessment documenting absence of PD for participants who do not have PD & were still on study at the time of an analysis/removed from study prior to documentation of TP. Participants started new antitumor treatment prior to documentation of PD were censored at last disease assessment prior to start of new treatment.	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	DOR: Time from first documentation of OR(sCR,CR,VGPR/PR) to first documentation of PD/death due to any cause, whichever came first. PD: Objective evidence of tumor progression(TP) (based on serum, urine/BM assessments) &/clinical progression/ investigator. sCR: CR, normal FLC ratio & absence of clonal cells in bone marrow by IC/IF. CR: Negative immunofixation of serum&urine, disappearance of any STP, &<5% plasma cells in bone marrow. VGPR: Serum & UMP detectable by immunofixation but not on electrophoresis/ >= 90% reduction(R) in SMP level+UMP level <100 mg/24 hour, PR: >=50%R of SMP & R in 24-hour UMP by >=90% or to <200 mg/24 hour. DOR: censored on date of last disease assessment documenting absence of PD for participants who do not have PD & were still on study at the time of an analysis/removed from study prior to documentation of TP. Participants started new antitumor treatment prior to documentation of PD were censored at last disease assessment prior to start of new treatment.	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	PFS: Time from the start of any study treatment to first documentation of DP or to death due to any cause, whichever comes first. DP included objective evidence of tumor progression (based on serum, urine or BM assessments) and/or clinical progression per investigator. PFS was censored on the date of the last disease assessment documenting absence of PD for participants who do not have disease progression and are still on study at the time of an analysis, or discontinuation of study prior to documentation of tumor progression. Participants who have started a new antitumor treatment prior to documentation of PD were censored at the last disease assessment prior to start of new treatment. Participants lacking an evaluation of tumor response after their first dose had their event time censored as 1 day.	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	PFS: Time from the start of any study treatment to first documentation of DP or to death due to any cause, whichever comes first. DP included objective evidence of tumor progression (based on serum, urine or BM assessments) and/or clinical progression per investigator. PFS was censored on the date of the last disease assessment documenting absence of PD for participants who do not have disease progression and are still on study at the time of an analysis, or discontinuation of study prior to documentation of tumor progression. Participants who have started a new antitumor treatment prior to documentation of PD were censored at the last disease assessment prior to start of new treatment. Participants lacking an evaluation of tumor response after their first dose had their event time censored as 1 day.	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	PFS: Time from the start of any study treatment to first documentation of DP or to death due to any cause, whichever comes first. DP included objective evidence of tumor progression (based on serum, urine or BM assessments) and/or clinical progression per investigator. PFS was censored on the date of the last disease assessment documenting absence of PD for participants who do not have disease progression and are still on study at the time of an analysis, or discontinuation of study prior to documentation of tumor progression. Participants who have started a new antitumor treatment prior to documentation of PD were censored at the last disease assessment prior to start of new treatment. Participants lacking an evaluation of tumor response after their first dose had their event time censored as 1 day.	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	PFS: Time from the start of any study treatment to first documentation of DP or to death due to any cause, whichever comes first. DP included objective evidence of tumor progression (based on serum, urine or BM assessments) and/or clinical progression per investigator. PFS was censored on the date of the last disease assessment documenting absence of PD for participants who do not have disease progression and are still on study at the time of an analysis, or discontinuation of study prior to documentation of tumor progression. Participants who have started a new antitumor treatment prior to documentation of PD were censored at the last disease assessment prior to start of new treatment. Participants lacking an evaluation of tumor response after their first dose had their event time censored as 1 day.	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	OS was defined as the time from the start of any study treatment to the date of death due to any cause. OS was calculated as date of death minus date of first dose of any study treatment plus 1. OS for participants who were alive at their date of last contact, including those lost to follow-up, were censored at the date of last contact. If the last recorded date where a participant was known to be alive is the date of first dose of any study treatment, survival time was censored on the date of first dose of any study treatment (i.e., OS duration of 1 day).	From date of start of study treatment until date of death or censoring date (maximum up to 45 months)
OS: Part B	OS was defined as the time from the start of any study treatment to the date of death due to any cause. OS was calculated as date of death minus date of first dose of any study treatment plus 1. OS for participants who were alive at their date of last contact, including those lost to follow-up, were censored at the date of last contact. If the last recorded date where a participant was known to be alive is the date of first dose of any study treatment, survival time was censored on the date of first dose of any study treatment (i.e., OS duration of 1 day).	From date of start of study treatment until date of death or censoring date (maximum up to 34 months)
OS: Part C	OS was defined as the time from the start of any study treatment to the date of death due to any cause. OS was calculated as date of death minus date of first dose of any study treatment plus 1. OS for participants who were alive at their date of last contact, including those lost to follow-up, were censored at the date of last contact. If the last recorded date where a participant was known to be alive is the date of first dose of any study treatment, survival time was censored on the date of first dose of any study treatment (i.e., OS duration of 1 day).	From date of start of study treatment until date of death or censoring date (maximum up to 37 months)
OS: Part D	OS was defined as the time from the start of any study treatment to the date of death due to any cause. OS was calculated as date of death minus date of first dose of any study treatment plus 1. OS for participants who were alive at their date of last contact, including those lost to follow-up, were censored at the date of last contact. If the last recorded date where a participant was known to be alive is the date of first dose of any study treatment, survival time was censored on the date of first dose of any study treatment (i.e., OS duration of 1 day).	From date of start of study treatment until date of death or censoring date (maximum up to 20 months)

Collaborators and Investigators

• Sponsor: Seagen Inc.
• Investigators: Study Director: Jonathan Hayman, MD, Seagen Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2018
• Primary Completion (Actual): November 9, 2023
• Study Completion (Actual): November 9, 2023

Study Registration Dates

• First Submitted: June 12, 2018
• First Submitted That Met QC Criteria: July 3, 2018
• First Posted (Actual): July 10, 2018

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: November 1, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Immunotherapy; RRMM; Seattle Genetics; Myeloma; Antibodies, monoclonal; Hematologic diseases; Antigens, BCMA
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Dexamethasone; Pomalidomide
• Other Study ID Numbers: SGNBCMA-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No