MTD Study of Vaccine BP-GMAX-CD1 Plus AP1903 to Treat Castrate Resistant Prostate Cancer

A Phase I, Non-randomized, Multiple Dose, Dose Escalation Study of the Safety, PK, PD and Efficacy of Therapeutic Vaccine, BP-GMAX-CD1, Plus Activating Agent, AP1903, in Patients With Castrate Resistant Prostate Cancer

This is a Phase I, non-randomized, multiple-dose, 3+3 dose-escalation study of the safety, pharmacokinetics, biomarkers, preliminary efficacy and patient-reported outcomes of therapeutic vaccine, BPX-101 (formerly BP-GMAX-CD1), plus activating agent, AP1903, in patients with castrate resistant prostate cancer.

Study Overview

• Status: Completed
• Conditions: Castrate Resistant Prostate Cancer (CRPC)
• Intervention / Treatment: Biological: BPX-101; Drug: AP1903

Detailed Description

Patients will be screened within 6 weeks prior to Week 1. A total of 3 cohorts, consisting of 3 to 6 patients each, are planned to receive five to eight intradermal (ID) injections totaling 1 mL up to 1.6mL of BPX-101 at 3 doses levels for an initial 6 doses.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center Houston, CRU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Males ≥ 18 years of age
2. Histological diagnosis of adenocarcinoma of the prostate
3. Documented evidence of distant metastasis of disease
4. No more than 1 prior chemotherapeutic, biologic or combination treatment regimen (including vitamin D analogues) for CRPC. If previously treated, patients must be recovered from all toxicities prior to entry into the study.
5. Patients must have current or historical evidence of disease progression concomitant with surgical (orchiectomy) or medical castration (LHRH analogue); anti-androgen withdrawal (4 weeks for flutamide and 6 weeks for nilutamide or bicalutamide) is necessary only for patients on antiandrogens and a duration of response to antiandrogens > 3months;
6. Testosterone < 50 ng/dL achieved via medical or surgical castration. Patients receiving medical castration therapy must continue such therapy throughout the study.
7. Adequate hematologic, renal and liver function:
8. Negative serology tests for human immunodeficiency virus (HIV-1 and 2), human T-cell lymphotropic virus (HTLV-1), hepatitis B surface antigen (HBsAg) and hepatitis C (HCV)
9. Karnofsky Performance Score (KPS) ≥ 70%
10. Life expectancy > 6 months
11. Written informed consent obtained prior to the initiation of study procedures

Exclusion Criteria:

1. The presence of brain metastases, pleural effusions or ascites
2. Pathologic long-bone fractures, imminent pathologic long-bone fracture (cortical erosion on radiography > 50%), or spinal cord compression
3. A history of stage III or greater cancer, excluding prostate cancer. Basal or squamous cell skin cancers must have been adequately treated and the patient must be disease-free at the time of registration. Patients with a history of stage I or II other cancers must have been adequately treated and been disease-free for 3 years at the time of registration.
4. More than 1 prior chemotherapy, biologic or combination treatment regimen (including vitamin D analogues) for CRPC
5. Any treatment with radiopharmaceuticals, e.g. Strontium-89 and Samarium-153
6. Ketoconazole or antiandrogens (flutamide, nilutamide, bicalutamide) within 2 weeks prior to registration. Patients who demonstrate an anti-androgen withdrawal response, defined as a > 25% drop in PSA within 4 weeks (flutamide) or 6 weeks (nilutamide, bicalutamide) of stopping a non-steroidal anti-androgen, are not eligible until the PSA rises above the nadir observed after anti-androgen withdrawal.
7. Initiation of bisphosphonate therapy within 28 days prior to registration. Patients taking bisphosphonates should not have their dosing regimen altered unless medically warranted.
8. A requirement for systemic steroid or other immunosuppressive therapy for any reason.
9. Treatment with any of the following medications or interventions < 28 days prior to Screening
10. Treatment with any investigational vaccine within 2 years prior to Screening, or treatment with any other investigational product within 28 days prior to Screening
11. Any antibiotic therapy or infection within 1 week prior to Screening, including unexplained fever (temperature ≥ 100.5F or 38.1C)
12. History of autoimmune disease
13. Serious ongoing chronic or acute illness
14. Any medical intervention or other condition which, in the opinion of the Principal Investigator and/or the Bellicum Medical Monitor, could compromise adherence with study requirements

Other Criteria Apply however are not listed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Dose escalation; Cohort 1: BPX-101, 4 x 10*6 cells administered every other week for 6 cycles Cohort 2: BPX-101, 12.5 x 10*6 cells administered every other week for 6 cycles Cohort 3: BPX-101, 25 x 10*6 cells administered every other week for 6 cycles Cohort 4: BPX-101, 25 x 10*6 cells administered every 4 weeks for 3 cycles At 24 hours after each vaccination, a single dose of the activating agent, AP1903 for Injection, will be administered at a fixed dose of 0.4 mg/kg via intravenous (IV) infusion over 2 hours.

Biological: BPX-101; Vaccine; Other Names: N/Ap; Drug: AP1903; Activating agent, infusion; Other Names: N/Ap

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose of BPX-101 and AP1903	To determine the maximum tolerated dose (MTD) of BPX-101 and AP1903 when administered 24 hours apart	1 Year
Safety and tolerability of BPX-101 and AP1903	To determine other measures of safety and tolerability of BPX-101 and AP1903 when administered 24 hours apart to patients with castrate resistant prostate cancer (CRPC).	1 Year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of AP1903	To determine the pharmacokinetics of AP1903 when administered 24 hours after BPX-101	1 Year
Immune responses and their association with clinical outcome	To assess immune responses and their association with clinical outcome as measured by changes in levels of interferon gamma (IFN)-producing T cells, the cytotoxic T lymphocyte (CTL) response, cytokines (IFN, IL-4, IL-10), activation markers, and other markers	2 Years
PSA response and PSA dynamics	To assess PSA response and PSA dynamics (change in velocity, doubling time)	1 Year
Number of circulating tumor cells (CTC)	To assess reduction in the number of circulating tumor cells (CTC)	1 Year
Cancer-related pain	To assess cancer-related pain	1 Year
Pain medication usage	To assess pain medication usage	1 Year
Preliminary efficacy of BPX-101 at the maximum tolerated dose (MTD)	To determine preliminary efficacy of BPX-101 at the maximum tolerated dose (MTD), based on tumor assessments using computed tomography (CT) or magnetic resonance imaging (MRI) and radionuclide bone scans	2 Years

Collaborators and Investigators

• Sponsor: Bellicum Pharmaceuticals
• Collaborators: M.D. Anderson Cancer Center; The University of Texas Health Science Center, Houston; Baylor College of Medicine; Memorial Hermann Hospital
• Investigators: Principal Investigator: Guru Sonpavde, MD, University of Texas Health Science Center Houston - CCTS

Publications and helpful links

Helpful Links

• Bellicum Pharmaceuticals Home Page

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: March 24, 2009
• First Submitted That Met QC Criteria: March 24, 2009
• First Posted (Estimate): March 25, 2009

Study Record Updates

• Last Update Posted (Actual): October 8, 2019
• Last Update Submitted That Met QC Criteria: October 4, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: BP-PC-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No