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

Study Overview
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Brief Summary
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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
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Phase 1: Cell dose escalation to identify the maximum dose of BPX-603 administered without or with rimiducid. 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.

Official Title
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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

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

Intervention / Treatment
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* Biological: chimeric antigen receptor (CAR) T cell therapy


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HER2-targeted dual-switch CAR-T cells<br>Subjects 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. | Biological: chimeric antigen receptor (CAR) T cell therapy<br>* HER2-targeted dual-switch CAR-T cells<br>* Other names: autologous CAR-T;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects experiencing Dose Limiting Toxicities at increasing doses of BPX-603 | Dose limiting toxicities are defined as BPX-603-related adverse events. | 35 days from time of BPX-603 infusion | 
| Maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) | Identify the optimal dose of BPX-603 for Phase 2. | through Phase 1 completion, up to 2 years | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HER2, CAR-T, breast cancer, solid tumors, gastric cancer