Clinical Trials /

Safety and Activity Study of HER2-Targeted Dual Switch CAR-T Cells (BPX-603) in Subjects With HER2-Positive Solid Tumors

NCT04650451

Description:

This is a Phase 1/2, open-label, multicenter, non-randomized study to investigate the safety, tolerability, and clinical activity of HER2-specific dual-switch CAR-T cells, BPX-603, administered with rimiducid to subjects with previously treated, locally advanced or metastatic solid tumors which are HER2 amplified/overexpressed.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Safety and Activity Study of HER2-Targeted Dual Switch CAR-T Cells (BPX-603) in Subjects With HER2-Positive Solid Tumors
  • Official Title: A Phase 1/2, Open-Label, Multicenter, Non-Randomized, Safety and Activity Study of HER2-Targeted Dual Switch CAR-T Cells (BPX-603) In Subjects With Previously Treated Advanced HER2-Positive Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: BPX603-201A
  • NCT ID: NCT04650451

Conditions

  • HER-2 Gene Amplification
  • HER2-positive Gastric Cancer
  • HER2-positive Breast Cancer
  • HER-2 Protein Overexpression
  • Solid Tumor, Adult

Interventions

DrugSynonymsArms
chimeric antigen receptor (CAR) T cell therapyCAR-T, BPX-603, autologous CAR-THER2-targeted dual-switch CAR-T cells

Purpose

This is a Phase 1/2, open-label, multicenter, non-randomized study to investigate the safety, tolerability, and clinical activity of HER2-specific dual-switch CAR-T cells, BPX-603, administered with rimiducid to subjects with previously treated, locally advanced or metastatic solid tumors which are HER2 amplified/overexpressed.

Detailed Description

      -  Phase 1: Cell dose escalation to identify the maximum dose of BPX-603 administered
           without or with rimiducid (fixed dose at 0.4 mg/kg per infusion). The first subject in
           each dose cohort will receive BPX-603 alone (without rimiducid) in order to assess
           safety of the CAR-T monotherapy.

        -  Phase 2: Indication-specific dose expansion to assess the safety, pharmacodynamics
           (including BPX-603 persistence and response to temsirolimus as applicable), and clinical
           activity at the recommended dose for expansion (RDE) identified in Phase 1 in various
           HER2+ solid tumors.

        -  During Phase 1 or 2, temsirolimus (single IV dose at 25 mg) may be administered
           following BPX-603 infusion in response to treatment-emergent toxicity in order to
           activate the iRC9 safety switch.
    

Trial Arms

NameTypeDescriptionInterventions
HER2-targeted dual-switch CAR-T cellsExperimentalSubjects will receive one dose of BPX-603 on Day 1, followed by rimiducid IV infusion weekly (as tolerated) starting on Day 8 and continued until treatment discontinuation criteria are met.
  • chimeric antigen receptor (CAR) T cell therapy

Eligibility Criteria

        Inclusion Criteria:

          -  Documented evidence of HER2 amplification/overexpression by local testing.

          -  Histologically or cytologically confirmed diagnosis of a locally advanced unresectable
             or metastatic HER2+ solid tumor malignancy for which standard treatment is no longer
             effective, does not exist, or subject is ineligible.

          -  Subjects with a solid tumor malignancy for which HER2-targeted therapy is approved as
             a standard treatment (e.g., breast, gastric cancers) must have received prior
             treatment with approved HER2-directed therapy.

          -  Measurable disease (at least one target lesion) per RECIST v1.1.

          -  Life expectancy > 12 weeks.

          -  ECOG 0-1.

          -  Adequate organ function.

        Exclusion Criteria:

          -  Symptomatic, untreated, or actively progressing central nervous system metastases.

          -  Prior CAR T cell or other genetically-modified T cell therapy.

          -  Impaired cardiac function or clinically significant cardiac disease.

          -  Symptomatic intrinsic lung disease or those with extensive tumor involvement of the
             lungs.

          -  Severe intercurrent infection.

          -  Pregnant or breastfeeding.

          -  Known HIV positivity.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Proportion of subjects experiencing Dose Limiting Toxicities at increasing doses of BPX-603
Time Frame:35 days from time of BPX-603 infusion
Safety Issue:
Description:Dose limiting toxicities are defined as BPX-603-related adverse events.

Secondary Outcome Measures

Measure:Persistence of HER2-CAR T cells (cell counts)
Time Frame:measured over time from baseline through study completion, up to 5 years
Safety Issue:
Description:The persistence over time of BPX-603 CAR T cells in the peripheral blood as determined by flow cytometry (% CAR+ cells).
Measure:Expansion of HER2-CAR T cells (vector copy number)
Time Frame:measured over time from baseline through study completion, up to 5 years
Safety Issue:
Description:The expansion over time of BPX-603 CAR T cells in the peripheral blood as determined by qPCR (copies/ug gDNA).
Measure:Antitumor activity of BPX-603
Time Frame:through study completion, up to 5 years
Safety Issue:
Description:Overall response rate

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Bellicum Pharmaceuticals

Trial Keywords

  • HER2
  • CAR-T
  • breast cancer
  • solid tumors
  • gastric cancer

Last Updated

December 2, 2020