Description:
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.
Title
- Brief Title: Safety and Activity Study of HER2-Targeted Dual Switch CAR-T Cells (BPX-603) in Subjects With HER2-Positive Solid Tumors
- Official Title: 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
Clinical Trial IDs
- ORG STUDY ID:
BPX603-201A
- NCT ID:
NCT04650451
Conditions
- HER-2 Gene Amplification
- HER2-positive Gastric Cancer
- HER2-positive Breast Cancer
- HER-2 Protein Overexpression
- Solid Tumor, Adult
Interventions
Drug | Synonyms | Arms |
---|
chimeric antigen receptor (CAR) T cell therapy | CAR-T, BPX-603, autologous CAR-T | HER2-targeted dual-switch CAR-T cells |
Purpose
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 (fixed dose at 0.4 mg/kg per infusion). 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.
Trial Arms
Name | Type | Description | Interventions |
---|
HER2-targeted dual-switch CAR-T cells | Experimental | 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. | - chimeric antigen receptor (CAR) T cell therapy
|
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 v1.1.
- 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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Proportion of subjects experiencing Dose Limiting Toxicities at increasing doses of BPX-603 |
Time Frame: | 35 days from time of BPX-603 infusion |
Safety Issue: | |
Description: | Dose limiting toxicities are defined as BPX-603-related adverse events. |
Secondary Outcome Measures
Measure: | Persistence of HER2-CAR T cells (cell counts) |
Time Frame: | measured over time from baseline through study completion, up to 5 years |
Safety Issue: | |
Description: | The persistence over time of BPX-603 CAR T cells in the peripheral blood as determined by flow cytometry (% CAR+ cells). |
Measure: | Expansion of HER2-CAR T cells (vector copy number) |
Time Frame: | measured over time from baseline through study completion, up to 5 years |
Safety Issue: | |
Description: | The expansion over time of BPX-603 CAR T cells in the peripheral blood as determined by qPCR (copies/ug gDNA). |
Measure: | Antitumor activity of BPX-603 |
Time Frame: | through study completion, up to 5 years |
Safety Issue: | |
Description: | Overall response rate |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Bellicum Pharmaceuticals |
Trial Keywords
- HER2
- CAR-T
- breast cancer
- solid tumors
- gastric cancer
Last Updated
April 26, 2021