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

Phase 1

Suspended

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

Brief Summary: 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. 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
HER2-targeted dual-switch CAR-T cells	chimeric antigen receptor (CAR) T cell therapy	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Locations (7): Winship Cancer Institute at Emory University
🇺🇸
Atlanta, Georgia, United States
John Theurer Cancer Center, Hackensack University Medical Center
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Hackensack, New Jersey, United States
University of Chicago
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Chicago, Illinois, United States
City of Hope National Medical Center
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Duarte, California, United States
University of California San Diego (UCSD)
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La Jolla, California, United States
The University of Texas MD Anderson Cancer Center
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Houston, Texas, United States
Roswell Park Cancer Institute
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Buffalo, New York, United States