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Study of ACTR087 in Combination With SEA-BCMA in Subjects With Relapsed or Refractory Multiple Myeloma

Primary Purpose

Multiple Myeloma, Multiple Myeloma in Relapse, Refractory Multiple Myeloma

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
ACTR087
SEA-BCMA
Sponsored by
Cogent Biosciences, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring BCMA, SEA-BCMA, B Cell Maturation Antigen, ACTR, ACTR087, T cell, T cell product, relapsed, refractory, multiple myeloma, adoptive T cells, autologous, gene therapy, cell therapy

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Signed written informed consent obtained prior to study procedures
  • Histologically- or cytologically-confirmed relapsed or refractory multiple myeloma (MM) with measurable disease
  • Must have received at least 3 prior lines of therapy to include treatment with a proteasome inhibitor (eg, bortezomib, carfilzomib, or ixazomib) and an immunomodulatory agent (eg, lenalidomide, pomalidomide) unless double-refractory to both; and a hematopoietic stem cell transplant (HSCT), for those subjects considered HSCT-eligible.
  • Quantitative serum IgG levels for subjects with IgG MM must not exceed the institutional upper limit of normal (ULN)
  • ECOG 0 or 1
  • Life expectancy of at least 6 months
  • Absolute neutrophil (ANC) count greater than 1000/ µL
  • Platelet count greater than 50,000/µL
  • Estimated GFR >30mL/min/1.73m2

Exclusion Criteria:

  • Known active central nervous system (CNS) involvement by MM
  • Systemic rheumatic or autoimmune diseases or acute or chronic infections
  • Uncontrolled thromboembolic events or recent severe hemorrhage
  • Subjects who are currently using more than 5mg/day of prednisone (or an equivalent glucocorticoid exceeding physiologic replacement levels)

  • Prior treatment as follows:

    • T cell-directed antibody therapy (eg. Alemtuzumab, anti-thymocyte globulin) within 6 months of enrollment
    • Any prior myeloma-directed therapy including cytotoxic chemotherapy, biologic therapy, or radiotherapy within 2 weeks of enrollment
    • Any mAb or other protein therapeutic containing Fc-domains within 4 weeks of enrollment
    • Experimental agents within 3 half-lives prior to enrollment, unless progression is documented on therapy
    • Prior BCMA-directed investigational agents at any time
    • Prior cell or gene therapy, excluding transfers of genetically unmodified autologous cells (eg. Hematopoietic stem cell transplantation), at any time; or prior allogeneic HSCT at any time
  • Pregnant or breastfeeding

Sites / Locations

  • Mayo Clinic
  • Mayo Clinic
  • Indiana Blood and Marrow Transplantation
  • Tufts Medical Center
  • Ohio State University Wexner Medical Center
  • Baylor Scott & White
  • Medical College of Wisconsin

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ACTR087 in combination with SEA-BCMA

Arm Description

Outcomes

Primary Outcome Measures

Safety and tolerability of ACTR087 in combination with SEA-BCMA
Composite outcome measure assessed by committee review of dose limiting toxicities (DLTs), incidence and severity of AEs and clinically significant abnormalities of laboratory values
Determination of recommended Phase 2 dosing regimen
Review of DLTs, Maximum tolerated contour (MTC), incidence and severity of AEs and clinically significant abnormalities of laboratory values

Secondary Outcome Measures

Safety of SEA-BCMA as measured by incidence of Treatment Emergent Adverse Events (TEAEs)
Review of all TEAEs, including incidence and severity of AEs, DLTs and clinically significant abnormalities of laboratory values
Anti-myeloma activity as measured by overall response rate (per IMWG response criteria)
Anti-myeloma activity as measured by duration of response
Anti-myeloma activity as measured by progression-free survival
Anti-myeloma activity as measured by overall survival
Assessment of persistence of ACTR087 as measured by flow cytometry and qPCR
Assessment of ACTR087 phenotype and function as measured by flow cytometry
Assessment of induction of inflammatory markers and cytokines/chemokines after ACTR087 administration
Levels of inflammatory markers, cytokines/chemokines
SEA-BCMA PK
SEA-BCMA plasma concentration
Assessment of anti-drug antibodies (ADA) after SEA-BCMA administration
Incidence of ADAs to SEA-BCMA

Full Information

First Posted
August 22, 2017
Last Updated
March 27, 2020
Sponsor
Cogent Biosciences, Inc.
Collaborators
Seagen Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03266692
Brief Title
Study of ACTR087 in Combination With SEA-BCMA in Subjects With Relapsed or Refractory Multiple Myeloma
Official Title
A Phase 1 Study of ACTR087, an Autologous T Cell Product, in Combination With SEA-BCMA, a Monoclonal Antibody, in Subjects With Relapsed or Refractory Multiple Myeloma
Study Type
Interventional

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Terminated
Why Stopped
Business reasons
Study Start Date
February 22, 2018 (Actual)
Primary Completion Date
October 1, 2019 (Actual)
Study Completion Date
October 1, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cogent Biosciences, Inc.
Collaborators
Seagen Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a phase 1, multi-center, single-arm, open-label study evaluating the safety, tolerability, and anti-myeloma activity of ACTR087 (an autologous T cell product) in combination with SEA-BCMA (a monoclonal antibody) in subjects with relapsed or refractory Multiple Myeloma.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma, Multiple Myeloma in Relapse, Refractory Multiple Myeloma
Keywords
BCMA, SEA-BCMA, B Cell Maturation Antigen, ACTR, ACTR087, T cell, T cell product, relapsed, refractory, multiple myeloma, adoptive T cells, autologous, gene therapy, cell therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ACTR087 in combination with SEA-BCMA
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
ACTR087
Intervention Description
Autologous T cell product
Intervention Type
Biological
Intervention Name(s)
SEA-BCMA
Intervention Description
B-cell maturation antigen (BCMA)-directed antibody
Primary Outcome Measure Information:
Title
Safety and tolerability of ACTR087 in combination with SEA-BCMA
Description
Composite outcome measure assessed by committee review of dose limiting toxicities (DLTs), incidence and severity of AEs and clinically significant abnormalities of laboratory values
Time Frame
28 days
Title
Determination of recommended Phase 2 dosing regimen
Description
Review of DLTs, Maximum tolerated contour (MTC), incidence and severity of AEs and clinically significant abnormalities of laboratory values
Time Frame
52 weeks
Secondary Outcome Measure Information:
Title
Safety of SEA-BCMA as measured by incidence of Treatment Emergent Adverse Events (TEAEs)
Description
Review of all TEAEs, including incidence and severity of AEs, DLTs and clinically significant abnormalities of laboratory values
Time Frame
21 days
Title
Anti-myeloma activity as measured by overall response rate (per IMWG response criteria)
Time Frame
52 weeks
Title
Anti-myeloma activity as measured by duration of response
Time Frame
52 weeks
Title
Anti-myeloma activity as measured by progression-free survival
Time Frame
52 weeks
Title
Anti-myeloma activity as measured by overall survival
Time Frame
52 weeks
Title
Assessment of persistence of ACTR087 as measured by flow cytometry and qPCR
Time Frame
52 weeks
Title
Assessment of ACTR087 phenotype and function as measured by flow cytometry
Time Frame
52 weeks
Title
Assessment of induction of inflammatory markers and cytokines/chemokines after ACTR087 administration
Description
Levels of inflammatory markers, cytokines/chemokines
Time Frame
52 weeks
Title
SEA-BCMA PK
Description
SEA-BCMA plasma concentration
Time Frame
52 weeks
Title
Assessment of anti-drug antibodies (ADA) after SEA-BCMA administration
Description
Incidence of ADAs to SEA-BCMA
Time Frame
52 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed written informed consent obtained prior to study procedures Histologically- or cytologically-confirmed relapsed or refractory multiple myeloma (MM) with measurable disease Must have received at least 3 prior lines of therapy to include treatment with a proteasome inhibitor (eg, bortezomib, carfilzomib, or ixazomib) and an immunomodulatory agent (eg, lenalidomide, pomalidomide) unless double-refractory to both; and a hematopoietic stem cell transplant (HSCT), for those subjects considered HSCT-eligible. Quantitative serum IgG levels for subjects with IgG MM must not exceed the institutional upper limit of normal (ULN) ECOG 0 or 1 Life expectancy of at least 6 months Absolute neutrophil (ANC) count greater than 1000/ µL Platelet count greater than 50,000/µL Estimated GFR >30mL/min/1.73m2 Exclusion Criteria: Known active central nervous system (CNS) involvement by MM Systemic rheumatic or autoimmune diseases or acute or chronic infections Uncontrolled thromboembolic events or recent severe hemorrhage Subjects who are currently using more than 5mg/day of prednisone (or an equivalent glucocorticoid exceeding physiologic replacement levels) Prior treatment as follows: T cell-directed antibody therapy (eg. Alemtuzumab, anti-thymocyte globulin) within 6 months of enrollment Any prior myeloma-directed therapy including cytotoxic chemotherapy, biologic therapy, or radiotherapy within 2 weeks of enrollment Any mAb or other protein therapeutic containing Fc-domains within 4 weeks of enrollment Experimental agents within 3 half-lives prior to enrollment, unless progression is documented on therapy Prior BCMA-directed investigational agents at any time Prior cell or gene therapy, excluding transfers of genetically unmodified autologous cells (eg. Hematopoietic stem cell transplantation), at any time; or prior allogeneic HSCT at any time Pregnant or breastfeeding
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jessica Sachs, MD
Organizational Affiliation
Cogent Biosciences, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Mayo Clinic
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Facility Name
Mayo Clinic
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Indiana Blood and Marrow Transplantation
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46327
Country
United States
Facility Name
Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Ohio State University Wexner Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Baylor Scott & White
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Study of ACTR087 in Combination With SEA-BCMA in Subjects With Relapsed or Refractory Multiple Myeloma

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