Back to resultsSafety and Activity Study of HER2-Targeted Dual Switch CAR-T Cells (BPX-603) in Subjects With HER2-Positive Solid Tumors
Primary Purpose
HER-2 Gene Amplification, HER2-positive Gastric Cancer, HER2-positive Breast Cancer
Status
Suspended
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
chimeric antigen receptor (CAR) T cell therapy
Sponsored by
About this trial
This is an interventional treatment trial for HER-2 Gene Amplification focused on measuring HER2, CAR-T, breast cancer, solid tumors, gastric cancer
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.
Sites / Locations
- City of Hope National Medical Center
- University of California San Diego (UCSD)
- Winship Cancer Institute at Emory University
- University of Chicago
- John Theurer Cancer Center, Hackensack University Medical Center
- Roswell Park Cancer Institute
- The University of Texas MD Anderson Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
HER2-targeted dual-switch CAR-T cells
Arm 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.
Outcomes
Primary Outcome Measures
Proportion of subjects experiencing Dose Limiting Toxicities at increasing doses of BPX-603
Dose limiting toxicities are defined as BPX-603-related adverse events.
Maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE)
Identify the optimal dose of BPX-603 for Phase 2.
Secondary Outcome Measures
Persistence of HER2-CAR T cells (cell counts)
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)
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
Overall response rate
Full Information
NCT ID
NCT04650451
First Posted
November 20, 2020
Last Updated
April 18, 2023
Sponsor
Bellicum Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT04650451
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Suspended
Why Stopped
Due to a Dose Limiting Toxicity in another sister trial with same technology.
Study Start Date
December 7, 2020 (Actual)
Primary Completion Date
December 31, 2025 (Anticipated)
Study Completion Date
January 2, 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bellicum Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HER-2 Gene Amplification, HER2-positive Gastric Cancer, HER2-positive Breast Cancer, HER-2 Protein Overexpression, Solid Tumor, Adult
Keywords
HER2, CAR-T, breast cancer, solid tumors, gastric cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
220 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
HER2-targeted dual-switch CAR-T cells
Arm Type
Experimental
Arm 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.
Intervention Type
Biological
Intervention Name(s)
chimeric antigen receptor (CAR) T cell therapy
Other Intervention Name(s)
CAR-T, BPX-603, autologous CAR-T
Intervention Description
HER2-targeted dual-switch CAR-T cells
Primary Outcome Measure Information:
Title
Proportion of subjects experiencing Dose Limiting Toxicities at increasing doses of BPX-603
Description
Dose limiting toxicities are defined as BPX-603-related adverse events.
Time Frame
35 days from time of BPX-603 infusion
Title
Maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE)
Description
Identify the optimal dose of BPX-603 for Phase 2.
Time Frame
through Phase 1 completion, up to 2 years
Secondary Outcome Measure Information:
Title
Persistence of HER2-CAR T cells (cell counts)
Description
The persistence over time of BPX-603 CAR T cells in the peripheral blood as determined by flow cytometry (% CAR+ cells).
Time Frame
measured over time from baseline through study completion, up to 5 years
Title
Expansion of HER2-CAR T cells (vector copy number)
Description
The expansion over time of BPX-603 CAR T cells in the peripheral blood as determined by qPCR (copies/ug gDNA).
Time Frame
measured over time from baseline through study completion, up to 5 years
Title
Antitumor activity of BPX-603
Description
Overall response rate
Time Frame
through study completion, up to 5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Facility Information:
Facility Name
City of Hope National Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
University of California San Diego (UCSD)
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
Winship Cancer Institute at Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
322972
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
John Theurer Cancer Center, Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
The University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Safety and Activity Study of HER2-Targeted Dual Switch CAR-T Cells (BPX-603) in Subjects With HER2-Positive Solid Tumors
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