NCT03680560

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
6

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Mar 2019

Geographic Reach
1 country

6 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 14, 2018

Completed
7 days until next milestone

First Posted

Study publicly available on registry

September 21, 2018

Completed
6 months until next milestone

Study Start

First participant enrolled

March 13, 2019

Completed
1 year until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 12, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 12, 2020

Completed
Last Updated

March 31, 2020

Status Verified

March 1, 2020

Enrollment Period

1 year

First QC Date

September 14, 2018

Last Update Submit

March 27, 2020

Conditions

Keywords

HER2ACTRACTR087ACTR707T cellT cell productadoptive T cellsgene therapybreast cancergastric cancergastro esophageal cancerimmunotherapysolid tumoradenoid cystic carcinoma

Outcome Measures

Primary Outcomes (2)

  • 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 Outcomes (10)

  • 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

  • +5 more secondary outcomes

Study Arms (1)

ACTR T cell product in combination with trastuzumab

EXPERIMENTAL
Biological: ACTR T Cell ProductDrug: Trastuzumab

Interventions

Autologous Antibody-Coupled T Cell Receptor (ACTR) T Cell Product (ACTR707 or ACTR087)

ACTR T cell product in combination with trastuzumab

monoclonal antibody targeting HER2

ACTR T cell product in combination with trastuzumab

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

Yale Smilow Cancer Hospital

New Haven, Connecticut, 06511, United States

Location

Miami University Cancer Center

Miami, Florida, 33136, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Sarah Cannon Research Institute/Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

Baylor Scott & White Medical Center

Dallas, Texas, 75201, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

MeSH Terms

Conditions

Breast NeoplasmsStomach NeoplasmsCarcinoma, Adenoid Cystic

Interventions

Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesGastrointestinal NeoplasmsDigestive System NeoplasmsDigestive System DiseasesGastrointestinal DiseasesStomach DiseasesAdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Glen Weiss, MD

    Cogent Biosciences, Inc.

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 14, 2018

First Posted

September 21, 2018

Study Start

March 13, 2019

Primary Completion

March 12, 2020

Study Completion

March 12, 2020

Last Updated

March 31, 2020

Record last verified: 2020-03

Locations