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

Phase 1

Terminated

• Conditions: Multiple Myeloma; Multiple Myeloma in Relapse; Refractory Multiple Myeloma
• Interventions: Biological: ACTR087; Biological: SEA-BCMA

• Registration Number: NCT03266692
• Lead Sponsor: Cogent Biosciences, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-08-22
• Study First Submitted QC: 2017-08-28
• Study First Posted: 2017-08-30
• Study Start: 2018-02-22
• Primary Completion: 2019-10-01
• Study Completion: 2019-10-01
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-27
• Last Update Posted: 2020-03-30

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 15

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ACTR087 in combination with SEA-BCMA	SEA-BCMA	-
ACTR087 in combination with SEA-BCMA	ACTR087	-

Primary Outcome Measures

Name	Time	Method
Safety and tolerability of ACTR087 in combination with SEA-BCMA	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
Determination of recommended Phase 2 dosing regimen	52 weeks	Review of DLTs, Maximum tolerated contour (MTC), incidence and severity of AEs and clinically significant abnormalities of laboratory values

Secondary Outcome Measures

Name	Time	Method
Anti-myeloma activity as measured by overall survival	52 weeks
Assessment of persistence of ACTR087 as measured by flow cytometry and qPCR	52 weeks
Assessment of ACTR087 phenotype and function as measured by flow cytometry	52 weeks
Assessment of anti-drug antibodies (ADA) after SEA-BCMA administration	52 weeks	Incidence of ADAs to SEA-BCMA
Safety of SEA-BCMA as measured by incidence of Treatment Emergent Adverse Events (TEAEs)	21 days	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)	52 weeks
Anti-myeloma activity as measured by duration of response	52 weeks
Anti-myeloma activity as measured by progression-free survival	52 weeks
Assessment of induction of inflammatory markers and cytokines/chemokines after ACTR087 administration	52 weeks	Levels of inflammatory markers, cytokines/chemokines
SEA-BCMA PK	52 weeks	SEA-BCMA plasma concentration

Trial Locations

Locations (6)

Baylor Scott & White; 🇺🇸 Dallas, Texas, United States

Indiana Blood and Marrow Transplantation; 🇺🇸 Indianapolis, Indiana, United States

Ohio State University Wexner Medical Center; 🇺🇸 Columbus, Ohio, United States

Mayo Clinic; 🇺🇸 Jacksonville, Florida, United States

Tufts Medical Center; 🇺🇸 Boston, Massachusetts, United States

Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States