Description:
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 (pancreatic and 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.
Title
- Brief Title: Safety and Activity Study of PSCA-Targeted CAR-T Cells (BPX-601) in Subjects With Selected Advanced Solid Tumors
- 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 IDs
- ORG STUDY ID:
BP-012
- NCT ID:
NCT02744287
Conditions
- Metastatic Castration-resistant Prostate Cancer
- Metastatic Prostate Cancer
- Metastatic Pancreatic Ductal Adenocarcinoma
- Metastatic Pancreatic Cancer
- Metastatic Pancreatic Adenocarcinoma
Interventions
| Drug | Synonyms | Arms |
|---|
| BPX-601 | | Arm 1: Phase 1 Dose Escalation |
| Rimiducid | AP1903 | Arm 1: Phase 1 Dose Escalation |
Purpose
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 (pancreatic and 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
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 (pancreatic or 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 (fixed dose of 0.4 mg/kg per infusion).
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Arm 1: Phase 1 Dose Escalation | Experimental | Participants with advanced pancreatic or 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. | |
| Arm 2: Phase 2 Dose Expansion | Experimental | Participants with advanced pancreatic or 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. | |
Eligibility Criteria
Inclusion Criteria:
- Metastatic pancreatic cancer with tumor progression within 6 months of the most recent
anti-cancer treatment and documented positive tumor expression of PSCA, and prior
treatment with first or second-line therapy; or,
- 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:
- Pancreatic cancer with islet cell neoplasms or symptomatic/untreated coagulopathy.
- 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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Dose Limiting Toxicity |
| Time Frame: | 4 weeks after first rimiducid infusion (i.e., Day 35) |
| Safety Issue: | |
| Description: | Incidence of dose limiting toxicity |
Secondary Outcome Measures
| Measure: | Pharmacodynamics (PD) of BPX-601 |
| Time Frame: | up to 1 year after treatment |
| Safety Issue: | |
| Description: | Change from baseline in pharmacodynamic blood biomarkers - markers of BPX-601 CAR-T cells |
| Measure: | Antitumor activity of BPX-601 |
| Time Frame: | 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 |
| Safety Issue: | |
| Description: | 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 |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Bellicum Pharmaceuticals |
Trial Keywords
- prostate stem cell antigen
- BPX-601
- AP1903
- CAR-T
- PSCA-CAR
- castration-resistant prostate cancer
- rimiducid
- pancreatic cancer
- PSCA
- CRPC
- mCRPC
- PDAC
Last Updated
April 26, 2021
