Clinical trial NCT03680560: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Solid Tumor
HER-2 Protein Overexpression
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
Lead sponsor: Cogent Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2018-09-21
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
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
timeFrame: 42 days
measure: Determination of recommended phase 2 dose (RP2D) regimen
timeFrame: 42 days
Secondary outcomes:
measure: Anti-tumor activity as measured by overall response rate (ORR) per iRECIST
timeFrame: 52 weeks
measure: Anti-tumor activity as measured best overall response (BOR)
timeFrame: 52 weeks
measure: Anti-tumor activity as measured by duration of response (DOR)
timeFrame: 52 weeks
measure: Anti-tumor activity as measured by progression-free survival (PFS)
timeFrame: 52 weeks
measure: Anti-tumor activity as measured by overall survival (OS)
timeFrame: 52 weeks
measure: Assessment of persistence of ACTR as measured by flow cytometry
timeFrame: 52 weeks
measure: Assessment of persistence of ACTR as measured by quantitative polymerase chain reaction (qPCR)
timeFrame: 52 weeks
measure: Assessment of ACTR phenotype and function as measured by flow cytometry
timeFrame: 52 weeks
measure: Assessment of induction of inflammatory markers and cytokines/chemokines after ACTR T cell product administration
timeFrame: 52 weeks
measure: Trastuzumab pharmacokinetics (PK)
timeFrame: 52 weeks
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale Smilow Cancer Hospital
state: Connecticut
city: Miami
country: United States
facility: Miami University Cancer Center
state: Florida
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Nashville
country: United States
facility: Sarah Cannon Research Institute/Tennessee Oncology, PLLC
state: Tennessee
city: Dallas
country: United States
facility: Baylor Scott & White Medical Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Cogent Biosciences, Inc.
name: Glen Weiss, MD
role: STUDY_DIRECTOR
References: