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

Sponsor

Cogent Biosciences, Inc. (Industry)

Overall Status

Terminated

CT.gov ID

NCT03266692

Collaborator

Seagen Inc. (Industry)

Enrollment

Locations

Arm

19.3

Actual Duration (Months)

2.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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

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 :

Feb 22, 2018

Actual Primary Completion Date :

Oct 1, 2019

Actual Study Completion Date :

Oct 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

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

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

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]
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 [52 weeks]
Levels of inflammatory markers, cytokines/chemokines
SEA-BCMA PK [52 weeks]
SEA-BCMA plasma concentration
Assessment of anti-drug antibodies (ADA) after SEA-BCMA administration [52 weeks]
Incidence of ADAs to SEA-BCMA

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Phoenix	Arizona	United States	85054
2	Mayo Clinic	Jacksonville	Florida	United States	32224
3	Indiana Blood and Marrow Transplantation	Indianapolis	Indiana	United States	46327
4	Tufts Medical Center	Boston	Massachusetts	United States	02111
5	Ohio State University Wexner Medical Center	Columbus	Ohio	United States	43210
6	Baylor Scott & White	Dallas	Texas	United States	75246
7	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226