Clinical trial NCT04650451: 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
Overall status: SUSPENDED
Phase: PHASE1
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
Lead sponsor: Bellicum Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2020-12-02
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Proportion of subjects experiencing Dose Limiting Toxicities at increasing doses of BPX-603
timeFrame: 35 days from time of BPX-603 infusion
measure: Maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE)
timeFrame: through Phase 1 completion, up to 2 years
Secondary outcomes:
measure: Persistence of HER2-CAR T cells (cell counts)
timeFrame: measured over time from baseline through study completion, up to 5 years
measure: Expansion of HER2-CAR T cells (vector copy number)
timeFrame: measured over time from baseline through study completion, up to 5 years
measure: Antitumor activity of BPX-603
timeFrame: through study completion, up to 5 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: La Jolla
country: United States
facility: University of California San Diego (UCSD)
state: California
city: Atlanta
country: United States
facility: Winship Cancer Institute at Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Hackensack
country: United States
facility: John Theurer Cancer Center, Hackensack University Medical Center
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
Study officials:
References: