Safety and Activity Study of PSCA-Targeted CAR-T Cells (BPX-601) in Subjects With Selected Advanced Solid Tumors

Metastatic Castration-resistant Prostate Cancer Clinical Trial

Official title:

A Phase 1/2 Feasibility, Safety, and Activity Study of PSCA-Specific Chimeric Antigen Receptor Engineered T Cells (BPX-601) in Subjects With Previously Treated Advanced Solid Tumors

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT02744287
• Other study ID #: BP-012
• Status: Suspended
• Phase: Phase 1/Phase 2
• Start date: November 2016
• Est. completion date: February 2026

Study information

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

Clinical Trial Summary

The purpose of this study is to evaluate the safety and activity of BPX-601 CAR-T cells in participants with previously treated advanced solid tumors (prostate) expressing high levels of prostate stem cell antigen (PSCA). Participants' T cells are modified to recognize and target the PSCA tumor marker on cancer cells.

Description:

The goal of this study is to characterize the feasibility, safety, and clinical activity of PSCA-specific CAR-T cells, BPX-601, administered with rimiducid to subjects with previously treated, PSCA-positive advanced solid tumors (prostate). BPX-601 CAR-T cells are genetically engineered to express a chimeric antigen receptor (CAR) to target the PSCA antigen and a rimiducid-inducible signaling domain which functions as a molecular "go-switch" to enhance activation and proliferation.

Phase 1: Cell dose escalation to identify the maximum dose of BPX-601 administered with single or repeat doses of rimiducid.

Phase 2: Indication-specific dose expansion to assess the safety, pharmacodynamics (including BPX-601 persistence), and clinical activity at the recommended dose identified in Phase 1 in various PSCA-expressing solid tumors.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 151
• Est. completion date: February 2026
• Est. primary completion date: October 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Metastatic castration-resistant prostate cancer (mCRPC), with progressive disease per PCWG3 criteria during or following the direct prior line of therapy.

• Measurable disease per RECIST v1.1 at baseline; subjects with mCRPC with bone only metastases must have measurable PSA.

• Age =18 years.

• Life expectancy > 12 weeks.

• ECOG 0-1

• Adequate organ function.

Exclusion Criteria:

• Prostate cancer with unstable bone lesions or symptomatic/untreated coagulopathy, or history of > Grade 2 hematuria within the previous 6 months.

• Prior CAR T cell or other genetically-modified T cell therapy. Prior treatment with an immune-based therapy for the treatment of prostate cancer, including cancer vaccine therapies are allowable.

• Symptomatic, untreated, or actively progressing central nervous system metastases.

• Impaired cardiac function or clinically significant cardiac disease.

• Pregnant or breastfeeding.

• Participant requires chronic, systemic steroid therapy.

• Severe intercurrent infection.

• Known HIV positivity.

Related Conditions & MeSH terms

• Metastatic Castration-resistant Prostate Cancer
• Metastatic Prostate Cancer
• Prostatic Neoplasms

Intervention

Biological:
• BPX-601
Autologous T cells genetically modified with retrovirus vector containing PSCA-specific CAR and an inducible MyD88/Cluster Designation (CD)40 (iMC) co-stimulatory domain

Drug:
• Rimiducid
Dimerizer infusion to activate the iMC of the BPX-601 cells for improved proliferation and persistence

Locations

Country	Name	City	State
United States	Emory Winship Cancer Institute	Atlanta	Georgia
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Chicago Medicine	Chicago	Illinois
United States	Baylor Sammons Cancer Center	Dallas	Texas
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Duke University	Durham	North Carolina
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	Columbia University Medical Center	New York	New York
United States	University of Nebraska	Omaha	Nebraska
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Bellicum Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Limiting Toxicity	Incidence of dose limiting toxicity	4 weeks after first rimiducid infusion (i.e., Day 35)
Primary	Treatment emergent adverse events (AEs) and serious AEs (SAEs)	Number of participants with adverse events (AEs) and serious AEs (SAEs) assessed for severity using NCI CTCAE v4.03	180 days after BPX-601 treatment up to 15 years
Primary	Maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D)	Identify the optimal dose of BPX-601 with rimiducid for Phase 2	through Phase 1 completion, up to 5 years
Secondary	Pharmacodynamics (PD) of BPX-601	Change from baseline in pharmacodynamic blood biomarkers - markers of BPX-601 CAR-T cells	up to 1 year after treatment
Secondary	Antitumor activity of BPX-601	Percentage of subjects with objective response determined by the investigator according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or the Prostate Cancer Working Group 3 (PCWG3) criteria	From the time of BPX-601 cell infusion until confirmed disease progression or death due to any cause, the start of new anticancer therapy, or withdrawal, whichever comes first, as assessed for up to 5 years after the last subject has been enrolled