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

NCT03582033 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: SGNBCMA-001
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 13

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.

Conditions

Multiple Myeloma

Keywords

RRMM; Antibodies, monoclonal; Antigens, BCMA; Immunotherapy; Hematologic diseases; Myeloma; Seattle Genetics

Outcome Measures

Primary Outcomes (16)

• 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 Outcomes (33)

• 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

Study Arms (3)

Parts A and B: SEA-BCMA Monotherapy

EXPERIMENTAL

SEA-BCMA

Drug: SEA-BCMA

Part C: SEA-BCMA + Dexamethasone Combination Therapy

EXPERIMENTAL

SEA-BCMA + dexamethasone

Drug: SEA-BCMA; Drug: dexamethasone

Part D: SEA-BCMA + Pomalidomide + Dexamethasone Combination Therapy

EXPERIMENTAL

SEA-BCMA + dexamethasone + pomalidomide

Drug: SEA-BCMA; Drug: dexamethasone; Drug: pomalidomide

Interventions

SEA-BCMA DRUG

Given into the vein (IV; intravenously)

Part C: SEA-BCMA + Dexamethasone Combination Therapy; Part D: SEA-BCMA + Pomalidomide + Dexamethasone Combination Therapy; Parts A and B: SEA-BCMA Monotherapy

dexamethasone DRUG

Given by mouth (orally) or by IV

Part C: SEA-BCMA + Dexamethasone Combination Therapy; Part D: SEA-BCMA + Pomalidomide + Dexamethasone Combination Therapy

pomalidomide DRUG

Given orally

Part D: SEA-BCMA + Pomalidomide + Dexamethasone Combination Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Seagen Inc.: lead

Study Sites (13)

Stanford University School of Medicine

Palo Alto, California, 94304, United States

Location

Rocky Mountain Cancer Centers - Aurora

Aurora, Colorado, 80012, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Holden Comprehensive Cancer Center / University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

Washington University in St Louis

St Louis, Missouri, 63110, United States

Location

Weill Cornell Medicine

New York, New York, 10065, United States

Location

James P. Wilmot Cancer Center / University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Willamette Valley Cancer Institute and Research Center

Eugene, Oregon, 97401, United States

Location

Texas Oncology - Austin Midtown

Austin, Texas, 78705, United States

Location

Texas Oncology - Northeast Texas

Tyler, Texas, 75702, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Hematologic Diseases; Neoplasms, Plasma Cell

Interventions

Dexamethasone; pomalidomide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Seagen Inc.

medinfo@seagen.com

(855) 473-2436

Study Officials

• Jonathan Hayman, MD

  Seagen Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2018
• First Posted: July 10, 2018
• Study Start: November 1, 2018
• Primary Completion: November 9, 2023
• Study Completion: November 9, 2023
• Last Updated: December 24, 2024
• Results First Posted: December 24, 2024

Record last verified: 2024-10

Locations

US (13)