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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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ClinicalTrials.gov Identifier: NCT04650451
Recruitment Status : Recruiting
First Posted : December 2, 2020
Last Update Posted : April 26, 2021
Sponsor:
Information provided by (Responsible Party):
Bellicum Pharmaceuticals

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.

Condition or disease Intervention/treatment Phase
HER-2 Gene Amplification HER2-positive Gastric Cancer HER2-positive Breast Cancer HER-2 Protein Overexpression Solid Tumor, Adult Biological: chimeric antigen receptor (CAR) T cell therapy Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 220 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 7, 2020
Estimated Primary Completion Date : December 31, 2023
Estimated Study Completion Date : January 2, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: HER2-targeted dual-switch CAR-T cells
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.
Biological: chimeric antigen receptor (CAR) T cell therapy
HER2-targeted dual-switch CAR-T cells
Other Names:
  • CAR-T
  • BPX-603
  • autologous CAR-T




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. Persistence of HER2-CAR T cells (cell counts) [ Time Frame: 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).

  2. Expansion of HER2-CAR T cells (vector copy number) [ Time Frame: 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).

  3. Antitumor activity of BPX-603 [ Time Frame: through study completion, up to 5 years ]
    Overall response rate



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04650451


Contacts
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Contact: BPX-603 Study Team 832-384-1100 603enrolment@bellicum.com

Locations
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United States, California
City of Hope National Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Yuan Yuan, MD         
Principal Investigator: Yuan Yuan, MD         
United States, Georgia
Winship Cancer Institute at Emory University Recruiting
Atlanta, Georgia, United States, 322972
Contact: Mehmet Akce, MD         
Principal Investigator: Mehmet Akce, MD         
United States, New Jersey
John Theurer Cancer Center, Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Martin Gutierrez, MD         
Principal Investigator: Martin Gutierrez, MD         
United States, New York
Roswell Park Cancer Institute Not yet recruiting
Buffalo, New York, United States, 14263
Contact: Ann Grand'Maison, MD         
Principal Investigator: Ann Grand'Maison, MD         
United States, Rhode Island
Roger Williams Medical Center Not yet recruiting
Providence, Rhode Island, United States, 02908
Contact: Bharti Rathore, MD         
Principal Investigator: Bharti Rathore, MD         
United States, Texas
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Ecaterina I Dumbrava, MD         
Principal Investigator: Ecaterina I Dumbrava, MD         
Sponsors and Collaborators
Bellicum Pharmaceuticals
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Responsible Party: Bellicum Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04650451    
Other Study ID Numbers: BPX603-201A
First Posted: December 2, 2020    Key Record Dates
Last Update Posted: April 26, 2021
Last Verified: April 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Bellicum Pharmaceuticals:
HER2
CAR-T
breast cancer
solid tumors
gastric cancer
Additional relevant MeSH terms:
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Stomach Neoplasms
Neoplasms by Site
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases