HER-2 Protein Overexpression, Solid Tumor
Conditions
Keywords
HER2, ACTR, ACTR087, ACTR707, T cell, T cell product, adoptive T cells, gene therapy, breast cancer, gastric cancer, gastro esophageal cancer, immunotherapy, solid tumor, adenoid cystic carcinoma
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.
Interventions
BIOLOGICALACTR T Cell Product
Autologous Antibody-Coupled T Cell Receptor (ACTR) T Cell Product (ACTR707 or ACTR087)
DRUGTrastuzumab
monoclonal antibody targeting HER2
Sponsors
Cogent Biosciences, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Review of DLTs, maximum tolerated dose (MTD), incidence and severity of AEs and clinically significant abnormalities of laboratory values |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Levels of inflammatory markers, cytokines/chemokines in blood |
| Trastuzumab pharmacokinetics (PK) | 52 weeks | trastuzumab serum concentration, Area Under the Curve (AUC), trough levels |
Countries
United States
Outcome results
None listed