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

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

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.

Study Overview

• Status: Terminated
• Conditions: Multiple Myeloma; Refractory Multiple Myeloma; Multiple Myeloma in Relapse
• Intervention / Treatment: Biological: ACTR087; Biological: SEA-BCMA

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
  • Indiana
    • Indianapolis, Indiana, United States, 46327
      • Indiana Blood and Marrow Transplantation
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Wexner Medical Center
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor Scott & White
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	28 days
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	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	21 days
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
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 induction of inflammatory markers and cytokines/chemokines after ACTR087 administration	Levels of inflammatory markers, cytokines/chemokines	52 weeks
SEA-BCMA PK	SEA-BCMA plasma concentration	52 weeks
Assessment of anti-drug antibodies (ADA) after SEA-BCMA administration	Incidence of ADAs to SEA-BCMA	52 weeks

Collaborators and Investigators

• Sponsor: Cogent Biosciences, Inc.
• Collaborators: Seagen Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 22, 2018
• Primary Completion (ACTUAL): October 1, 2019
• Study Completion (ACTUAL): October 1, 2019

Study Registration Dates

• First Submitted: August 22, 2017
• First Submitted That Met QC Criteria: August 28, 2017
• First Posted (ACTUAL): August 30, 2017

Study Record Updates

• Last Update Posted (ACTUAL): March 30, 2020
• Last Update Submitted That Met QC Criteria: March 27, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: gene therapy; cell therapy; relapsed; refractory; autologous; T cell; multiple myeloma; BCMA; SEA-BCMA; B Cell Maturation Antigen; ACTR; ACTR087; T cell product; adoptive T cells
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: ATTCK-17-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No