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

• ClinicalTrials.gov Identifier: NCT03266692
• Recruitment Status: Terminated
• First Posted: August 30, 2017
• Last Update Posted: March 30, 2020
• Sponsor: Cogent Biosciences, Inc.
• Collaborator: Seagen Inc.
• Information provided by (Responsible Party): Cogent Biosciences, Inc.

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.

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma; Multiple Myeloma in Relapse; Refractory Multiple Myeloma	Biological: ACTR087; Biological: SEA-BCMA	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: February 22, 2018
• Actual Primary Completion Date: October 1, 2019
• Actual Study Completion Date: October 1, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: ACTR087 in combination with SEA-BCMA	Biological: ACTR087; Autologous T cell product; Biological: SEA-BCMA; B-cell maturation antigen (BCMA)-directed antibody

Outcome Measures

Primary Outcome Measures :

1. Safety and tolerability of ACTR087 in combination with SEA-BCMA [ Time Frame: 28 days ]
   Composite outcome measure assessed by committee review of dose limiting toxicities (DLTs), incidence and severity of AEs and clinically significant abnormalities of laboratory values
2. Determination of recommended Phase 2 dosing regimen [ Time Frame: 52 weeks ]
   Review of DLTs, Maximum tolerated contour (MTC), incidence and severity of AEs and clinically significant abnormalities of laboratory values

Secondary Outcome Measures :

1. Safety of SEA-BCMA as measured by incidence of Treatment Emergent Adverse Events (TEAEs) [ Time Frame: 21 days ]
   Review of all TEAEs, including incidence and severity of AEs, DLTs and clinically significant abnormalities of laboratory values
2. Anti-myeloma activity as measured by overall response rate (per IMWG response criteria) [ Time Frame: 52 weeks ]
3. Anti-myeloma activity as measured by duration of response [ Time Frame: 52 weeks ]
4. Anti-myeloma activity as measured by progression-free survival [ Time Frame: 52 weeks ]
5. Anti-myeloma activity as measured by overall survival [ Time Frame: 52 weeks ]
6. Assessment of persistence of ACTR087 as measured by flow cytometry and qPCR [ Time Frame: 52 weeks ]
7. Assessment of ACTR087 phenotype and function as measured by flow cytometry [ Time Frame: 52 weeks ]
8. Assessment of induction of inflammatory markers and cytokines/chemokines after ACTR087 administration [ Time Frame: 52 weeks ]
   Levels of inflammatory markers, cytokines/chemokines
9. SEA-BCMA PK [ Time Frame: 52 weeks ]
   SEA-BCMA plasma concentration
10. Assessment of anti-drug antibodies (ADA) after SEA-BCMA administration [ Time Frame: 52 weeks ]
    Incidence of ADAs to SEA-BCMA

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Arizona

Mayo Clinic

Phoenix, Arizona, United States, 85054

United States, Florida

Mayo Clinic

Jacksonville, Florida, United States, 32224

United States, Indiana

Indiana Blood and Marrow Transplantation

Indianapolis, Indiana, United States, 46327

United States, Massachusetts

Tufts Medical Center

Boston, Massachusetts, United States, 02111

United States, Ohio

Ohio State University Wexner Medical Center

Columbus, Ohio, United States, 43210

United States, Texas

Baylor Scott & White

Dallas, Texas, United States, 75246

United States, Wisconsin

Medical College of Wisconsin

Milwaukee, Wisconsin, United States, 53226

Sponsors and Collaborators

Cogent Biosciences, Inc.

Seagen Inc.

Investigators

• Study Director: Jessica Sachs, MD; Cogent Biosciences, Inc.

More Information

• Responsible Party: Cogent Biosciences, Inc.
• ClinicalTrials.gov Identifier: NCT03266692
• Other Study ID Numbers: ATTCK-17-01
• First Posted: August 30, 2017
• Last Update Posted: March 30, 2020
• Last Verified: March 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Cogent Biosciences, Inc.:

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

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases