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

Cogent Biosciences

Status and phase: Terminated; Phase 1

Conditions: Solid Tumor; HER-2 Protein Overexpression

Treatments: Biological: ACTR T Cell Product; Drug: Trastuzumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03680560

ATTCK-34-01

Details and patient eligibility

About

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.

Enrollment: 6 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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6 participants in 1 patient group

ACTR T cell product in combination with trastuzumab

Experimental group

Treatment:

Drug: Trastuzumab

Biological: ACTR T Cell Product