A Phase 1 Study of an Autologous ACTR T Cell Product in Combination With Trastuzumab, a Monoclonal Antibody, in Subjects With HER2-Positive Advanced Malignancies

Cogent Biosciences, Inc.6 sites in 1 country6 target enrollmentMarch 13, 2019

ConditionsSolid Tumor HER-2 Protein Overexpression

InterventionsACTR T Cell Product Trastuzumab

DrugsTrastuzumab

Overview

Phase: Phase 1
Intervention: ACTR T Cell Product
Conditions: Solid Tumor
Sponsor: Cogent Biosciences, Inc.
Enrollment: 6
Locations: 6
Primary Endpoint: Determination of recommended phase 2 dose (RP2D) regimen
Status: Terminated
Last Updated: 6 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a Phase 1, open-label, multi-center study to assess safety and determine the recommended phase 2 dose (RP2D) of ACTR T cell product (ACTR707 or ACTR087) in combination with trastuzumab, following lymphodepleting chemotherapy in subjects with HER2-positive advanced malignancies.

Registry

clinicaltrials.gov

Start Date

March 13, 2019

End Date

March 12, 2020

Last Updated

6 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Cogent Biosciences, Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Signed written informed consent obtained prior to study procedures
•Histologically-confirmed Her2 positive advanced solid tumor malignancy with documented disease progression during or immediately following the immediate prior therapy, or within 6 months of completing adjuvant therapy for subjects with breast cancer
•Subjects must have previously received adequate standard therapy for treatment of their malignancy
•For those with metastatic breast cancer, must have received HER2-directed therapy including trastuzumab, pertuzumab and ado-trastuzumab in any breast cancer disease setting
•For those with advanced gastric cancer, adequate prior treatment with HER2-directed chemotherapy is required
•At least 1 measurable lesion by iRECIST
•Able to provide fresh tumor biopsy or archived block specimen taken since time of most recent anti-HER2 mAb-directed therapy
•ECOG of 0 or 1
•Life expectancy ≥ 6 months
•LVEF ≥ 50% by MUGA or ECHO

Exclusion Criteria

•glioblastoma multiforme or other primary CNS tumors are excluded
•clinically significant cardiac disease
•clinically significant active infection
•clinical history, prior diagnosis, or overt evidence of autoimmune disease
•current use of more than 5mg/day of prednisone (or an equivalent glucocorticoid)
•Prior treatment as follows:
•prior cumulative doxorubicin dose greater than or equal to 300 mg/m\^2 or equivalent
•chemotherapy within 2 weeks of enrollment
•external beam radiation within 2 weeks of enrollment (28 days if CNS-directed therapy)
•any monoclonal antibody (mAb) or other protein therapeutic containing Fc-domains within 4 weeks of enrollment

Arms & Interventions

ACTR T cell product in combination with trastuzumab

Intervention: ACTR T Cell Product

ACTR T cell product in combination with trastuzumab

Intervention: Trastuzumab

Outcomes

Primary Outcomes

Determination of recommended phase 2 dose (RP2D) regimen

Time Frame: 42 days

Review of DLTs, maximum tolerated dose (MTD), incidence and severity of AEs and clinically significant abnormalities of laboratory values

Safety and tolerability of ACTR T cell product with trastuzumab as assessed by committee review of dose limiting toxicities (DLTs), incidence and severity of adverse events (AEs) and clinically significant abnormalities of laboratory values

Time Frame: 42 days

Secondary Outcomes

Anti-tumor activity as measured by overall response rate (ORR) per iRECIST(52 weeks)
Anti-tumor activity as measured best overall response (BOR)(52 weeks)
Anti-tumor activity as measured by duration of response (DOR)(52 weeks)
Anti-tumor activity as measured by progression-free survival (PFS)(52 weeks)
Anti-tumor activity as measured by overall survival (OS)(52 weeks)
Assessment of persistence of ACTR as measured by flow cytometry(52 weeks)
Assessment of persistence of ACTR as measured by quantitative polymerase chain reaction (qPCR)(52 weeks)
Assessment of ACTR phenotype and function as measured by flow cytometry(52 weeks)
Assessment of induction of inflammatory markers and cytokines/chemokines after ACTR T cell product administration(52 weeks)
Trastuzumab pharmacokinetics (PK)(52 weeks)