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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Metastatic Castration-resistant Prostate Cancer, Metastatic Prostate Cancer

Intervention / Treatment
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* Biological: BPX-601
* Drug: Rimiducid


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: Phase 1 Dose Escalation<br>Participants with advanced prostate cancer will receive an intravenous infusion of BPX-601 followed by one or more intravenous infusions of rimiducid. Dose escalation of BPX-601 will continue until the recommended cell dose level is reached. | Biological: BPX-601<br>* Autologous T cells genetically modified with retrovirus vector containing PSCA-specific CAR and an inducible MyD88/Cluster Designation (CD)40 (iMC) co-stimulatory domain<br>Drug: Rimiducid<br>* Dimerizer infusion to activate the iMC of the BPX-601 cells for improved proliferation and persistence<br>* Other names: AP1903;|
| Experimental: Arm 2: Phase 2 Dose Expansion<br>Participants with advanced prostate cancer will receive an intravenous infusion of BPX-601 at the recommended cell dose level followed by one or more intravenous infusions of rimiducid. | Biological: BPX-601<br>* Autologous T cells genetically modified with retrovirus vector containing PSCA-specific CAR and an inducible MyD88/Cluster Designation (CD)40 (iMC) co-stimulatory domain<br>Drug: Rimiducid<br>* Dimerizer infusion to activate the iMC of the BPX-601 cells for improved proliferation and persistence<br>* Other names: AP1903;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicity | Incidence of dose limiting toxicity | 4 weeks after first rimiducid infusion (i.e., Day 35) | 
| 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 | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PSCA, prostate stem cell antigen, BPX-601, AP1903, CAR-T, PSCA-CAR, castration-resistant prostate cancer, rimiducid, prostate cancer, CRPC, mCRPC