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
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- HER-2 Gene Amplification
- Sponsor
- Bellicum Pharmaceuticals
- Enrollment
- 220
- Locations
- 7
- Primary Endpoint
- Maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE)
- Status
- Suspended
- Last Updated
- 3 years ago
Overview
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.
Investigators
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.
- •Life expectancy \> 12 weeks.
- •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.
Outcomes
Primary Outcomes
Maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE)
Time Frame: 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
Time Frame: 35 days from time of BPX-603 infusion
Dose limiting toxicities are defined as BPX-603-related adverse events.
Secondary Outcomes
- Persistence of HER2-CAR T cells (cell counts)(measured over time from baseline through study completion, up to 5 years)
- Expansion of HER2-CAR T cells (vector copy number)(measured over time from baseline through study completion, up to 5 years)
- Antitumor activity of BPX-603(through study completion, up to 5 years)