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

Sponsors

Lead Sponsor: Unum Therapeutics Inc.

Source 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.

Overall Status Terminated
Start Date March 13, 2019
Completion Date March 12, 2020
Primary Completion Date March 12, 2020
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure 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 42 days
Secondary Outcome
Measure 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 52 weeks
Trastuzumab pharmacokinetics (PK) 52 weeks
Enrollment 6
Condition
Intervention

Intervention Type: Biological

Intervention Name: ACTR T Cell Product

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

Arm Group Label: ACTR T cell product in combination with trastuzumab

Intervention Type: Drug

Intervention Name: Trastuzumab

Description: monoclonal antibody targeting HER2

Arm Group Label: ACTR T cell product in combination with trastuzumab

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

- 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

Gender: All

Minimum Age: 18 Years

Maximum Age: 75 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Glen Weiss, MD Study Director Unum Therapeutics Inc.
Location
Facility:
Yale Smilow Cancer Hospital | New Haven, Connecticut, 06511, United States
Miami University Cancer Center | Miami, Florida, 33136, United States
The Ohio State University | Columbus, Ohio, 43210, United States
Sarah Cannon Research Institute/Tennessee Oncology, PLLC | Nashville, Tennessee, 37203, United States
Baylor Scott & White Medical Center | Dallas, Texas, 75201, United States
MD Anderson Cancer Center | Houston, Texas, 77030, United States
Location Countries

United States

Verification Date

March 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Number Of Arms 1
Arm Group

Label: ACTR T cell product in combination with trastuzumab

Type: Experimental

Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov