Due to a Dose Limiting Toxicity in another sister trial with same technology.

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.

• 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.

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.