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

Bellicum Pharmaceuticals

Status and phase: Suspended; Phase 1

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

Treatments: Biological: chimeric antigen receptor (CAR) T cell therapy

Study type: Interventional

Funder types: Industry

Identifiers

NCT04650451

BPX603-201A

Details and patient eligibility

About

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.

Full 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.

Enrollment: 220 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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220 participants in 1 patient group

HER2-targeted dual-switch CAR-T cells

Experimental group

Description:

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.

Treatment:

Biological: chimeric antigen receptor (CAR) T cell therapy