HER-2 Gene AmplificationPhase 1NCT04650451
Safety and Activity Study of HER2-Targeted Dual Switch CAR-T Cells (BPX-603) in Subjects With HER2-Positive Solid Tumors
A Phase 1 study testing chimeric antigen receptor (CAR) T cell therapy in people with HER-2 Gene Amplification and HER2-positive Gastric Cancer, run by Bellicum Pharmaceuticals at 7 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HER-2 Gene Amplification, HER2-positive Gastric Cancer, HER2-positive Breast Cancer
- What is being tested?
- chimeric antigen receptor (CAR) T cell therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 220 participants
- Where
- 7 sitesUnited States
- Study dates
- 7 Dec 2020to 2 Jan 2027
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Winship Cancer Institute at Emory University
Atlanta, Georgia, 322972
Roswell Park Cancer Institute
Buffalo, New York, 14263
University of Chicago
Chicago, Illinois, 60637
City of Hope National Medical Center
Duarte, California, 91010
John Theurer Cancer Center, Hackensack University Medical Center
Hackensack, New Jersey, 07601
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
University of California San Diego (UCSD)
La Jolla, California, 92093
About this study
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
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.
Read the 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.
- Conditions
- HER-2 Gene Amplification, HER2-positive Gastric Cancer, HER2-positive Breast Cancer, HER-2 Protein Overexpression, Solid Tumor, Adult
- Being tested
- chimeric antigen receptor (CAR) T cell therapy
- Keywords
- HER2, CAR-T, breast cancer, solid tumors, gastric cancer
- Medical subject headings
- Breast Neoplasms, Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
chimeric antigen receptor (CAR) T cell therapyBiological
Also called CAR-T, BPX-603, autologous CAR-T
HER2-targeted dual-switch CAR-T cells
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: chimeric antigen receptor (CAR) T cell therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of subjects experiencing Dose Limiting Toxicities at increasing doses of BPX-603
Dose limiting toxicities are defined as BPX-603-related adverse events.
Measured: 35 days from time of BPX-603 infusion
Maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE)
Identify the optimal dose of BPX-603 for Phase 2.
Measured: through Phase 1 completion, up to 2 years
Secondary outcomes (3)
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).
Measured: measured over time from baseline through study completion, up to 5 years
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).
Measured: measured over time from baseline through study completion, up to 5 years
Antitumor activity of BPX-603
Overall response rate
Measured: through study completion, up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2020
- Study start7 Dec 2020
- Primary completion31 Dec 2025 (estimated)
- Study completion2 Jan 2027 (estimated)
Why it stopped: Due to a Dose Limiting Toxicity in another sister trial with same technology.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HER-2 Gene AmplificationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 220 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bellicum Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04650451
- Sponsor's protocol ID
- BPX603-201A
- Status last verified
- Apr 2023
- First submitted
- 20 Nov 2020
- Last updated
- 20 Apr 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04650451
- Acronym / sponsor ID
- BPX603-201A
- Conditions
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Due to a Dose Limiting Toxicity in another sister trial with same technology.
- Enrolment
- 220 participants (estimated)
- Lead sponsor
- Bellicum PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 7 Dec 2020 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 2 Jan 2027 (estimated)
- First posted
- 2 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HER2-targeted dual-switch CAR-T cells | Experimental | Biological: chimeric antigen receptor (CAR) T cell therapySubjects 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| chimeric antigen receptor (CAR) T cell therapyAlso: CAR-T, BPX-603, autologous CAR-THER2-targeted dual-switch CAR-T cells | Biological | HER2-targeted dual-switch CAR-T cells |
Primary outcome
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.
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.
3 secondary outcomes
Persistence of HER2-CAR T cells (cell counts)
Time frame: measured over time from baseline through study completion, up to 5 years
Expansion of HER2-CAR T cells (vector copy number)
Time frame: measured over time from baseline through study completion, up to 5 years
Antitumor activity of BPX-603
Time frame: through study completion, up to 5 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing chimeric antigen receptor (CAR) T cell therapy in people with HER-2 Gene Amplification and HER2-positive Gastric Cancer, run by Bellicum Pharmaceuticals at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: paused, as of the sponsor's last update on 20 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of subjects experiencing Dose Limiting Toxicities at increasing doses of BPX-603 (time frame: 35 days from time of BPX-603 infusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2023.