Clinical Trials /

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

NCT03680560

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.

Related Conditions:
  • Breast Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

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

DrugSynonymsArms
ACTR T Cell ProductACTR T cell product in combination with trastuzumab
TrastuzumabACTR 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

NameTypeDescriptionInterventions
ACTR T cell product in combination with trastuzumabExperimental
  • 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:Recruiting
Lead Sponsor:Unum Therapeutics 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

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