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

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ClinicalTrials.gov Identifier: NCT03680560
Recruitment Status : Not yet recruiting
First Posted : September 21, 2018
Last Update Posted : September 21, 2018
Sponsor:
Information provided by (Responsible Party):
Unum Therapeutics Inc.

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.

Condition or disease Intervention/treatment Phase
Solid Tumor HER-2 Protein Overexpression Biological: ACTR T Cell Product Drug: Trastuzumab Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Estimated Study Start Date : December 2018
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : March 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Trastuzumab

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




Primary Outcome Measures :
  1. 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 ]
  2. 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


Secondary Outcome Measures :
  1. Anti-tumor activity as measured by overall response rate (ORR) per iRECIST [ Time Frame: 52 weeks ]
  2. Anti-tumor activity as measured best overall response (BOR) [ Time Frame: 52 weeks ]
  3. Anti-tumor activity as measured by duration of response (DOR) [ Time Frame: 52 weeks ]
  4. Anti-tumor activity as measured by progression-free survival (PFS) [ Time Frame: 52 weeks ]
  5. Anti-tumor activity as measured by overall survival (OS) [ Time Frame: 52 weeks ]
  6. Assessment of persistence of ACTR as measured by flow cytometry [ Time Frame: 52 weeks ]
  7. Assessment of persistence of ACTR as measured by quantitative polymerase chain reaction (qPCR) [ Time Frame: 52 weeks ]
  8. Assessment of ACTR phenotype and function as measured by flow cytometry [ Time Frame: 52 weeks ]
  9. Assessment of induction of inflammatory markers and cytokines/chemokines after ACTR T cell product administration [ Time Frame: 52 weeks ]
    Levels of inflammatory markers, cytokines/chemokines in blood

  10. Trastuzumab pharmacokinetics (PK) [ Time Frame: 52 weeks ]
    trastuzumab serum concentration, Area Under the Curve (AUC), trough levels



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03680560


Contacts
Contact: Iga Sienczylo (617) 917-4430 iga.sienczylo@unumrx.com
Contact: Jessica Sachs, MD (617) 286-6640 jessica.sachs@unumrx.com

Sponsors and Collaborators
Unum Therapeutics Inc.
Investigators
Study Director: Jessica Sachs, MD Unum Therapeutics Inc.

Additional Information:
Responsible Party: Unum Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT03680560     History of Changes
Other Study ID Numbers: ATTCK-34-01
First Posted: September 21, 2018    Key Record Dates
Last Update Posted: September 21, 2018
Last Verified: September 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Unum Therapeutics Inc.:
HER2
ACTR
ACTR087
ACTR707
T cell
T cell product
adoptive T cells
gene therapy
breast cancer
gastric cancer
gastro esophageal cancer
immunotherapy

Additional relevant MeSH terms:
Antibodies
Antibodies, Monoclonal
Trastuzumab
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents