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

• Sponsor: Bellicum Pharmaceuticals (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT02744287
• Collaborator: (none)
• Enrollment: 151
• Locations: 14
• Arms: 2
• Anticipated Duration (Months): 111
• Patients Per Site: 10.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Castration-resistant Prostate Cancer; Metastatic Prostate Cancer	Biological: BPX-601; Drug: Rimiducid	Phase 1/Phase 2

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 (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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 151 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Nov 1, 2016
• Anticipated Primary Completion Date: Oct 1, 2025
• Anticipated Study Completion Date: Feb 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1: Phase 1 Dose Escalation 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; 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; Other Names: AP1903
Experimental: Arm 2: Phase 2 Dose Expansion 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; 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; Other Names: AP1903

Outcome Measures

Primary Outcome Measures

1. Dose Limiting Toxicity [4 weeks after first rimiducid infusion (i.e., Day 35)]

   Incidence of dose limiting toxicity

2. Treatment emergent adverse events (AEs) and serious AEs (SAEs) [180 days after BPX-601 treatment up to 15 years]

   Number of participants with adverse events (AEs) and serious AEs (SAEs) assessed for severity using NCI CTCAE v4.03

3. Maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) [through Phase 1 completion, up to 5 years]

   Identify the optimal dose of BPX-601 with rimiducid for Phase 2

Secondary Outcome Measures

1. Pharmacodynamics (PD) of BPX-601 [up to 1 year after treatment]

   Change from baseline in pharmacodynamic blood biomarkers - markers of BPX-601 CAR-T cells

2. Antitumor activity of BPX-601 [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]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Moffitt Cancer Center	Tampa	Florida	United States	33612
2	Emory Winship Cancer Institute	Atlanta	Georgia	United States	30322
3	Rush University Medical Center	Chicago	Illinois	United States	60612
4	University of Chicago Medicine	Chicago	Illinois	United States	60637
5	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
6	University of Nebraska	Omaha	Nebraska	United States	68198
7	John Theurer Cancer Center, Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
8	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
9	Columbia University Medical Center	New York	New York	United States	10032
10	Duke University	Durham	North Carolina	United States	27705
11	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
12	Tennessee Oncology, PLLC	Nashville	Tennessee	United States	37203
13	Baylor Sammons Cancer Center	Dallas	Texas	United States	75246
14	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• Bellicum Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bellicum Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02744287
• Other Study ID Numbers: BP-012
• First Posted: Apr 20, 2016
• Last Update Posted: Aug 12, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Bellicum Pharmaceuticals: prostate stem cell antigen; BPX-601; AP1903; CAR-T; PSCA-CAR; castration-resistant prostate cancer; rimiducid; prostate cancer; PSCA; CRPC; mCRPC
• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

No Results Posted as of Aug 12, 2022