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

Solid Tumor, Adult Clinical Trial

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 Details — Status: Suspended

Administrative data

• NCT number: NCT04650451
• Other study ID #: BPX603-201A
• Status: Suspended
• Phase: Phase 1
• Start date: December 7, 2020
• Est. completion date: January 2, 2027

Study information

• Verified date: April 2023
• Source: Bellicum Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 amplified/overexpressed.

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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 220
• Est. completion date: January 2, 2027
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HER-2 Gene Amplification
• HER-2 Protein Overexpression
• HER2-positive Breast Cancer
• HER2-positive Gastric Cancer
• Solid Tumor, Adult
• Stomach Neoplasms

Intervention

Biological:
• chimeric antigen receptor (CAR) T cell therapy
HER2-targeted dual-switch CAR-T cells

Locations

Country	Name	City	State
United States	Winship Cancer Institute at Emory University	Atlanta	Georgia
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University of Chicago	Chicago	Illinois
United States	City of Hope National Medical Center	Duarte	California
United States	John Theurer Cancer Center, Hackensack University Medical Center	Hackensack	New Jersey
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of California San Diego (UCSD)	La Jolla	California

Sponsors (1)

Lead Sponsor	Collaborator
Bellicum Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of subjects experiencing Dose Limiting Toxicities at increasing doses of BPX-603	Dose limiting toxicities are defined as BPX-603-related adverse events.	35 days from time of BPX-603 infusion
Primary	Maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE)	Identify the optimal dose of BPX-603 for Phase 2.	through Phase 1 completion, up to 2 years
Secondary	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 over time from baseline through study completion, up to 5 years
Secondary	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 over time from baseline through study completion, up to 5 years
Secondary	Antitumor activity of BPX-603	Overall response rate	through study completion, up to 5 years