Clinical trial NCT02744287: 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
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE1
PHASE2
Conditions: Metastatic Castration-resistant Prostate Cancer
Metastatic Prostate Cancer
Keywords: prostate stem cell antigen
BPX-601
AP1903
CAR-T
PSCA-CAR
castration-resistant prostate cancer
rimiducid
prostate cancer
PSCA
CRPC
mCRPC
Lead sponsor: Bellicum Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2016-04-20
Enrollment: 151
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Dose Limiting Toxicity
timeFrame: 4 weeks after first rimiducid infusion (i.e., Day 35)
measure: Treatment emergent adverse events (AEs) and serious AEs (SAEs)
timeFrame: 180 days after BPX-601 treatment up to 15 years
measure: Maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D)
timeFrame: through Phase 1 completion, up to 5 years
Secondary outcomes:
measure: Pharmacodynamics (PD) of BPX-601
timeFrame: up to 1 year after treatment
measure: Antitumor activity of BPX-601
timeFrame: 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
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory Winship Cancer Institute
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medicine
state: Illinois
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Omaha
country: United States
facility: University of Nebraska
state: Nebraska
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: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Dallas
country: United States
facility: Baylor Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
Study officials:
References: