Safety and Activity Study of HER2-Targeted Dual Switch CAR-T Cells (BPX-603) in Subjects With HER2-Positive Solid Tumors

April 18, 2023 updated by: Bellicum Pharmaceuticals

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.

Study Overview

Status

Suspended

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

220

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope National Medical Center
      • La Jolla, California, United States, 92093
        • University of California San Diego (UCSD)
    • Georgia
      • Atlanta, Georgia, United States, 322972
        • Winship Cancer Institute at Emory University
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • John Theurer Cancer Center, Hackensack University Medical Center
    • New York
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute
    • Texas
      • Houston, Texas, United States, 77030
        • The University of Texas MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
35 days from time of BPX-603 infusion
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.
through Phase 1 completion, up to 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
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
The expansion over time of BPX-603 CAR T cells in the peripheral blood as determined by qPCR (copies/ug gDNA).
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
Overall response rate
through study completion, up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bellicum Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 7, 2020

Primary Completion (Anticipated)

December 31, 2025

Study Completion (Anticipated)

January 2, 2027

Study Registration Dates

First Submitted

November 20, 2020

First Submitted That Met QC Criteria

December 1, 2020

First Posted (Actual)

December 2, 2020

Study Record Updates

Last Update Posted (Actual)

April 20, 2023

Last Update Submitted That Met QC Criteria

April 18, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BPX603-201A

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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