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

Phase 1

Terminated

• Conditions: HER-2 Protein Overexpression; Solid Tumor
• Interventions: Biological: ACTR T Cell Product; Drug: Trastuzumab

• Registration Number: NCT03680560
• Lead Sponsor: Cogent Biosciences, 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-09-14
• Study First Submitted QC: 2018-09-19
• Study First Posted: 2018-09-21
• Study Start: 2019-03-13
• Status Verified: 2020-03
• Primary Completion: 2020-03-12
• Study Completion: 2020-03-12
• Last Update Submitted: 2020-03-27
• Last Update Posted: 2020-03-31

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 6

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ACTR T cell product in combination with trastuzumab	Trastuzumab	-
ACTR T cell product in combination with trastuzumab	ACTR T Cell Product	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (6)

Sarah Cannon Research Institute/Tennessee Oncology, PLLC; 🇺🇸 Nashville, Tennessee, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Yale Smilow Cancer Hospital; 🇺🇸 New Haven, Connecticut, United States

Miami University Cancer Center; 🇺🇸 Miami, Florida, United States

Baylor Scott & White Medical Center; 🇺🇸 Dallas, Texas, United States

The Ohio State University; 🇺🇸 Columbus, Ohio, United States