Description:
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.
Title
- Brief Title: Study of ACTR T Cell Product in Combination With Trastuzumab in Subjects With HER2-Positive Advanced Solid Tumor Cancers
- 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
Clinical Trial IDs
- ORG STUDY ID:
ATTCK-34-01
- NCT ID:
NCT03680560
Conditions
- Solid Tumor
- HER-2 Protein Overexpression
Interventions
Drug | Synonyms | Arms |
---|
ACTR T Cell Product | | ACTR T cell product in combination with trastuzumab |
Trastuzumab | | ACTR T cell product in combination with trastuzumab |
Purpose
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 Arms
Name | Type | Description | Interventions |
---|
ACTR T cell product in combination with trastuzumab | Experimental | | - ACTR T Cell Product
- 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
Maximum Eligible Age: | 75 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | 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 |
Safety Issue: | |
Description: | Review of DLTs, maximum tolerated dose (MTD), incidence and severity of AEs and clinically significant abnormalities of laboratory values |
Secondary Outcome Measures
Measure: | Anti-tumor activity as measured by overall response rate (ORR) per iRECIST |
Time Frame: | 52 weeks |
Safety Issue: | |
Description: | |
Measure: | Anti-tumor activity as measured best overall response (BOR) |
Time Frame: | 52 weeks |
Safety Issue: | |
Description: | |
Measure: | Anti-tumor activity as measured by duration of response (DOR) |
Time Frame: | 52 weeks |
Safety Issue: | |
Description: | |
Measure: | Anti-tumor activity as measured by progression-free survival (PFS) |
Time Frame: | 52 weeks |
Safety Issue: | |
Description: | |
Measure: | Anti-tumor activity as measured by overall survival (OS) |
Time Frame: | 52 weeks |
Safety Issue: | |
Description: | |
Measure: | Assessment of persistence of ACTR as measured by flow cytometry |
Time Frame: | 52 weeks |
Safety Issue: | |
Description: | |
Measure: | Assessment of persistence of ACTR as measured by quantitative polymerase chain reaction (qPCR) |
Time Frame: | 52 weeks |
Safety Issue: | |
Description: | |
Measure: | Assessment of ACTR phenotype and function as measured by flow cytometry |
Time Frame: | 52 weeks |
Safety Issue: | |
Description: | |
Measure: | Assessment of induction of inflammatory markers and cytokines/chemokines after ACTR T cell product administration |
Time Frame: | 52 weeks |
Safety Issue: | |
Description: | Levels of inflammatory markers, cytokines/chemokines in blood |
Measure: | Trastuzumab pharmacokinetics (PK) |
Time Frame: | 52 weeks |
Safety Issue: | |
Description: | trastuzumab serum concentration, Area Under the Curve (AUC), trough levels |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Terminated |
Lead Sponsor: | Cogent Biosciences, Inc. |
Trial 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
Last Updated
March 31, 2020