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

Solid Tumor Clinical Trial

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 Details — Status: Terminated

Administrative data

• NCT number: NCT03680560
• Other study ID #: ATTCK-34-01
• Status: Terminated
• Phase: Phase 1
• Start date: March 13, 2019
• Est. completion date: March 12, 2020

Study information

• Verified date: March 2020
• Source: Unum Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: March 12, 2020
• Est. primary completion date: March 12, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• HER-2 Protein Overexpression
• Solid Tumor

Intervention

Biological:
• ACTR T Cell Product
Autologous Antibody-Coupled T Cell Receptor (ACTR) T Cell Product (ACTR707 or ACTR087)

Drug:
• Trastuzumab
monoclonal antibody targeting HER2

Locations

Country	Name	City	State
United States	The Ohio State University	Columbus	Ohio
United States	Baylor Scott & White Medical Center	Dallas	Texas
United States	MD Anderson Cancer Center	Houston	Texas
United States	Miami University Cancer Center	Miami	Florida
United States	Sarah Cannon Research Institute/Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Yale Smilow Cancer Hospital	New Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Unum Therapeutics Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Determination of recommended phase 2 dose (RP2D) regimen	Review of DLTs, maximum tolerated dose (MTD), incidence and severity of AEs and clinically significant abnormalities of laboratory values	42 days
Secondary	Anti-tumor activity as measured by overall response rate (ORR) per iRECIST		52 weeks
Secondary	Anti-tumor activity as measured best overall response (BOR)		52 weeks
Secondary	Anti-tumor activity as measured by duration of response (DOR)		52 weeks
Secondary	Anti-tumor activity as measured by progression-free survival (PFS)		52 weeks
Secondary	Anti-tumor activity as measured by overall survival (OS)		52 weeks
Secondary	Assessment of persistence of ACTR as measured by flow cytometry		52 weeks
Secondary	Assessment of persistence of ACTR as measured by quantitative polymerase chain reaction (qPCR)		52 weeks
Secondary	Assessment of ACTR phenotype and function as measured by flow cytometry		52 weeks
Secondary	Assessment of induction of inflammatory markers and cytokines/chemokines after ACTR T cell product administration	Levels of inflammatory markers, cytokines/chemokines in blood	52 weeks
Secondary	Trastuzumab pharmacokinetics (PK)	trastuzumab serum concentration, Area Under the Curve (AUC), trough levels	52 weeks

External Links

•   Sponsor Website