Clinical trial NCT03582033: A Safety Study of SEA-BCMA in Patients With Multiple Myeloma
Official title: A Phase 1 Study of SEA-BCMA in Patients With Relapsed or Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: RRMM
Antibodies, monoclonal
Antigens, BCMA
Immunotherapy
Hematologic diseases
Myeloma
Seattle Genetics
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
First posted: 2018-07-10
Enrollment: 83
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 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)
measure: Number of Participants With TEAEs, TESAEs, Treatment Related TEAEs and >=Grade 3 TEAEs: Part B
timeFrame: 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)
measure: Number of Participants With TEAEs, TESAEs, Treatment Related TEAEs and >=Grade 3 TEAEs: Part C
timeFrame: 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)
measure: Number of Participants With TEAEs, TESAEs, Treatment Related TEAEs and >=Grade 3 TEAEs: Part D
timeFrame: 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)
measure: Number of Participants With Maximum Laboratory Toxicity Grade, by NCI-CTCAE v4.03- Serum Chemistry: Part A
timeFrame: 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)
measure: Number of Participants With Maximum Laboratory Toxicity Grade, by NCI-CTCAE v4.03- Serum Chemistry: Part B
timeFrame: 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)
measure: Number of Participants With Maximum Laboratory Toxicity Grade, by NCI-CTCAE v4.03- Serum Chemistry: Part C
timeFrame: 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)
measure: Number of Participants With Maximum Laboratory Toxicity Grade, by NCI-CTCAE v4.03- Serum Chemistry: Part D
timeFrame: 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)
measure: Number of Participants With Maximum Laboratory Toxicity Grade, by NCI-CTCAE v4.03- Hematology: Part A
timeFrame: 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)
measure: Number of Participants With Maximum Laboratory Toxicity Grade, by NCI-CTCAE v4.03- Hematology: Part B
timeFrame: 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)
measure: Number of Participants With Maximum Laboratory Toxicity Grade, by NCI-CTCAE v4.03- Hematology: Part C
timeFrame: 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)
measure: Number of Participants With Maximum Laboratory Toxicity Grade, by NCI-CTCAE v4.03- Hematology: Part D
timeFrame: 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)
measure: Number of Participants With Dose Limiting Toxicities (DLTs): Part A
timeFrame: Cycle 1 (28 days)
measure: Number of Participants With DLTs: Part B
timeFrame: Cycle 1 (28 days)
measure: Number of Participants With DLTs: Part C
timeFrame: Cycle 1 (28 days)
measure: Number of Participants With DLTs: Part D
timeFrame: Cycle 1 (28 days)
Secondary outcomes:
measure: Area Under the Serum Concentration-Time Curve From Time 0 to Day 14 (AUC0-14) of SEA-BCMA: Part A
timeFrame: 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
measure: Area Under the Serum Concentration-Time Curve From Time 0 to Day 7 (AUC0-7) of SEA-BCMA: Part A
timeFrame: 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
measure: AUC0-7 of SEA-BCMA: Part B
timeFrame: 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
measure: AUC0-7 of SEA-BCMA: Part C
timeFrame: 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
measure: AUC0-7 of SEA-BCMA: Part D
timeFrame: 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
measure: Maximum Observed Serum Concentration (Cmax) of SEA-BCMA: Part A
timeFrame: 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
measure: Cmax of SEA-BCMA: Part B
timeFrame: 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
measure: Cmax of SEA-BCMA: Part C
timeFrame: 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
measure: Cmax of SEA-BCMA: Part D
timeFrame: 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
measure: Number of Participants With SEA-BCMA Antitherapeutic Antibodies (ATA): Part A
timeFrame: Anytime during study (maximum up to 45 months)
measure: Number of Participants With SEA-BCMA, ATA: Part B
timeFrame: Anytime during study (maximum up to 34 months)
measure: Number of Participants With SEA-BCMA, ATA: Part C
timeFrame: Anytime during study (maximum up to 37 months)
measure: Number of Participants With SEA-BCMA, ATA: Part D
timeFrame: Anytime during study (maximum up to 20 months)
measure: Objective Response Rate (ORR) as Per the International Myeloma Working Group (IMWG) Uniform Response Criteria: Part A
timeFrame: 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)
measure: ORR as Per the IMWG Uniform Response Criteria: Part B
timeFrame: 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)
measure: ORR as Per the IMWG Uniform Response Criteria: Part C
timeFrame: 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)
measure: ORR as Per the IMWG Uniform Response Criteria: Part D
timeFrame: 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)
measure: Percentage of Participants With Best Overall Response (BOR) as Per the IMWG Uniform Response Criteria: Part A
timeFrame: 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)
measure: Percentage of Participants With BOR as Per the IMWG Uniform Response Criteria: Part B
timeFrame: 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)
measure: Percentage of Participants With BOR as Per the IMWG Uniform Response Criteria: Part C
timeFrame: 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)
measure: Percentage of Participants With BOR as Per the IMWG Uniform Response Criteria: Part D
timeFrame: 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)
measure: Duration of Objective Response (DOR) as Per the IMWG Uniform Response Criteria: Part A
timeFrame: 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)
measure: DOR as Per the IMWG Uniform Response Criteria: Part B
timeFrame: 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)
measure: DOR as Per the IMWG Uniform Response Criteria: Part C
timeFrame: 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)
measure: DOR as Per the IMWG Uniform Response Criteria: Part D
timeFrame: 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)
measure: Progression Free Survival (PFS): Part A
timeFrame: 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)
measure: PFS: Part B
timeFrame: 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)
measure: PFS: Part C
timeFrame: 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)
measure: PFS: Part D
timeFrame: 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)
measure: Overall Survival (OS): Part A
timeFrame: From date of start of study treatment until date of death or censoring date (maximum up to 45 months)
measure: OS: Part B
timeFrame: From date of start of study treatment until date of death or censoring date (maximum up to 34 months)
measure: OS: Part C
timeFrame: From date of start of study treatment until date of death or censoring date (maximum up to 37 months)
measure: OS: Part D
timeFrame: From date of start of study treatment until date of death or censoring date (maximum up to 20 months)
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University School of Medicine
state: California
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers - Aurora
state: Colorado
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center / University of Iowa
state: Iowa
city: Westwood
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Saint Louis
country: United States
facility: Washington University in St Louis
state: Missouri
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center / University of Rochester Medical Center
state: New York
city: Eugene
country: United States
facility: Willamette Valley Cancer Institute and Research Center
state: Oregon
city: Austin
country: United States
facility: Texas Oncology - Austin Midtown
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Northeast Texas
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: Seagen Inc.
name: Jonathan Hayman, MD
role: STUDY_DIRECTOR
References: