HER-2 Gene Amplification, HER2-positive Breast Cancer, HER2-positive Gastric Cancer, HER-2 Protein Overexpression, Solid Tumor, Adult
Conditions
Keywords
HER2, CAR-T, breast cancer, solid tumors, gastric cancer
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.
Interventions
BIOLOGICALchimeric antigen receptor (CAR) T cell therapy
HER2-targeted dual-switch CAR-T cells
Sponsors
Bellicum Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Outcome results
None listed