Clinical trial NCT03266692: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: 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
Lead sponsor: Cogent Biosciences, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Seagen Inc.
First posted: 2017-08-30
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Safety and tolerability of ACTR087 in combination with SEA-BCMA
timeFrame: 28 days
measure: Determination of recommended Phase 2 dosing regimen
timeFrame: 52 weeks
Secondary outcomes:
measure: Safety of SEA-BCMA as measured by incidence of Treatment Emergent Adverse Events (TEAEs)
timeFrame: 21 days
measure: Anti-myeloma activity as measured by overall response rate (per IMWG response criteria)
timeFrame: 52 weeks
measure: Anti-myeloma activity as measured by duration of response
timeFrame: 52 weeks
measure: Anti-myeloma activity as measured by progression-free survival
timeFrame: 52 weeks
measure: Anti-myeloma activity as measured by overall survival
timeFrame: 52 weeks
measure: Assessment of persistence of ACTR087 as measured by flow cytometry and qPCR
timeFrame: 52 weeks
measure: Assessment of ACTR087 phenotype and function as measured by flow cytometry
timeFrame: 52 weeks
measure: Assessment of induction of inflammatory markers and cytokines/chemokines after ACTR087 administration
timeFrame: 52 weeks
measure: SEA-BCMA PK
timeFrame: 52 weeks
measure: Assessment of anti-drug antibodies (ADA) after SEA-BCMA administration
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Indianapolis
country: United States
facility: Indiana Blood and Marrow Transplantation
state: Indiana
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Columbus
country: United States
facility: Ohio State University Wexner Medical Center
state: Ohio
city: Dallas
country: United States
facility: Baylor Scott & White
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Cogent Biosciences, Inc.
name: Jessica Sachs, MD
role: STUDY_DIRECTOR
References: