Study of ACTR T Cell Product in Combination With Trastuzumab in Subjects With HER2-Positive Advanced Solid Tumor Cancers

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

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.

Study Overview

• Status: Terminated
• Conditions: Solid Tumor; HER-2 Protein Overexpression
• Intervention / Treatment: Biological: ACTR T Cell Product; Drug: Trastuzumab

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale Smilow Cancer Hospital
  • Florida
    • Miami, Florida, United States, 33136
      • Miami University Cancer Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute/Tennessee Oncology, PLLC
  • Texas
    • Dallas, Texas, United States, 75201
      • Baylor Scott & White Medical Center
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 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-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
• Absolute neutrophil (ANC) count ≥ 1500/ µL
• Platelet count ≥ 100,000/µL
• Hemoglobin ≥ 9g/dL
• Estimated GFR >30mL/min/1.73m2

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
  • pertuzumab within 4 months of enrollment
  • Experimental agents within 3 half-lives or 28 days prior to enrollment, whichever is shorter
  • allogeneic hematopoietic stem cell transplant (HSCT)
  • prior infusion of a genetically modified therapy
• 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: ACTR T cell product in combination with trastuzumab	Biological: ACTR T Cell Product; Autologous Antibody-Coupled T Cell Receptor (ACTR) T Cell Product (ACTR707 or ACTR087); Drug: Trastuzumab; monoclonal antibody targeting HER2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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		42 days
Determination of recommended phase 2 dose (RP2D) regimen	Review of DLTs, maximum tolerated dose (MTD), incidence and severity of AEs and clinically significant abnormalities of laboratory values	42 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Levels of inflammatory markers, cytokines/chemokines in blood	52 weeks
Trastuzumab pharmacokinetics (PK)	trastuzumab serum concentration, Area Under the Curve (AUC), trough levels	52 weeks

Collaborators and Investigators

• Sponsor: Cogent Biosciences, Inc.
• Investigators: Study Director: Glen Weiss, MD, Cogent Biosciences, Inc.

Publications and helpful links

Helpful Links

• Sponsor Website

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 13, 2019
• Primary Completion (ACTUAL): March 12, 2020
• Study Completion (ACTUAL): March 12, 2020

Study Registration Dates

• First Submitted: September 14, 2018
• First Submitted That Met QC Criteria: September 19, 2018
• First Posted (ACTUAL): September 21, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 31, 2020
• Last Update Submitted That Met QC Criteria: March 27, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: breast cancer; immunotherapy; HER2; gene therapy; gastric cancer; solid tumor; T cell; adenoid cystic carcinoma; ACTR; ACTR087; T cell product; adoptive T cells; ACTR707; gastro esophageal cancer
• Additional Relevant MeSH Terms: Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab
• Other Study ID Numbers: ATTCK-34-01

Drug and device information, study documents

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