Safety & Immunogenicity of JNJ-64041809, a Live Attenuated Double-deleted Listeria Immunotherapy, in Participants With Metastatic Castration-resistant Prostate Cancer

NCT02625857 | Completed Phase 1 FDA Drug

• 2 other identifiers: CR10766864041809PCR1001
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this study is to find and evaluate the recommended Phase 2 dose (RP2D) of JNJ-64041809, a live attenuated double deleted (LADD) Listeria monocytogenes (bacteria in which two virulence genes, which encode molecules that help cause disease, have been removed) when administered intravenously to participants with metastatic castration-resistant prostate cancer (mCRPC).

Conditions

Prostatic Neoplasms, Castration-Resistant

Keywords

Prostatic Neoplasms, Castration-Resistant; JNJ-64041809; Listeria monocytogenes

Outcome Measures

Primary Outcomes (3)

• Part 1: Incidence of Dose-limiting-toxicity (DLT)

  Percentage of Participants who Experienced DLT will be evaluated. The DLT dose level is defined as an unacceptable level of toxicity as evidenced by a DLT rate of greater than or equal to (\>=) 33 percent (%).

  first 21 days after the first infusion

• Part 2: Antigen-specific T-cell Response

  Biomarker studies will be performed to evaluate immune responses to the vaccine after the first intravenous (IV) immunization.

  up to 1 year

• Part 1 and Part 2: Incidence of Adverse Events (AEs)

  An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Incidence was defined as the number of participants who experienced an adverse event within their period of participation in this study. Incidence of adverse events will be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE).

  From signing of informed consent form to 30 days after last dose of study drug

Secondary Outcomes (6)

• Part 1 and Part 2: Objective Response Rate (ORR)

  Baseline up to 30 days after last dose of study drug

• Part 1 and Part 2: Duration of Response (DOR)

  Baseline up to 30 days after last dose of study drug

• Part 1 and Part 2: Progression-free Survival (PFS)

  Baseline up to 30 days after last dose of study drug

• Part 1 and Part 2: Time to Prostate Specific Antigen (PSA) progression (TTPP)

  Baseline up to 30 days after last dose of study drug

• Part 1 and Part 2: Blood Culture Assessment of JNJ-64041809

  Periodically during treatment and up to one year after End of Treatment (EOT) visit

Study Arms (2)

Dose Cohort 1A and 1B

EXPERIMENTAL

JNJ-64041809 will be administered intravenously (IV) once every 21 days.

Biological: JNJ-64041809 (Cohort 1A and 1B)

Dose Cohort 2A and 2B

EXPERIMENTAL

JNJ-64041809 will be administered intravenously (IV) once every 21 days.

Biological: JNJ-64041809 (Cohort 2A and 2B)

Interventions

JNJ-64041809 (Cohort 1A and 1B) BIOLOGICAL

JNJ-64041809 will be administered IV at a lower dose in Cohort 1A (1x10\^8 colony forming units \[CFU\]) and at a higher dose in Cohort 1B (1x10\^9 CFU).

Dose Cohort 1A and 1B

JNJ-64041809 (Cohort 2A and 2B) BIOLOGICAL

JNJ-64041809 will be administered intravenously (IV) once every 21 days at the recommended dose as determined in Cohort 1A or 1B.

Dose Cohort 2A and 2B

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed adenocarcinoma of the prostate with progressive metastatic disease which, in the opinion of the investigator, requires initiation of new treatment. The assessment of disease progression can be based on either PSA rise, new or progressive soft tissue disease (based on computed tomography \[CT\] or magnetic resonance imaging \[MRI\] scans), or new or progressive bony disease based on radionuclide bone scan or 18F-sodium fluoride positron emission tomography/computed tomography \[NaF PET/CT\] scans). Participants being considered for Cohort 2B must, in addition, have primary or metastatic lesions amenable to tumor biopsies
• Must have received at least 2 prior approved therapies
• Ongoing androgen depletion therapy with a Gonadotropin Releasing Hormone analog or inhibitor, or orchiectomy (surgical or medical castration)
• Serum testosterone levels less than (\<) 50 nanogram per deciliter (ng/dL) determined within 4 weeks prior to start of study drug
• For participants previously treated with first generation anti-androgens (ie, flutamide, nilutamide, or bicalutamide), discontinuation of flutamide or nilutamide therapy must occur greater than (\>) 4 weeks (\>6 weeks for bicalutamide) prior to start of study drug with no evidence of an anti-androgen withdrawal response (no decline in serum PSA)

You may not qualify if:

• Untreated brain metastases. Participants must have completed treatment for brain metastasis, and be neurologically stable off steroids, for at least 28 days prior to first dose of study drug
• Untreated spinal cord compression
• History of listeriosis or vaccination with a listeria-based vaccine or prophylactic vaccine (example influenza, pneumococcal, diphtheria, tetanus, and pertussis \[dTP/dTAP\]) within 28 days of study treatment
• Known allergy to both penicillin and trimethoprim/sulfamethoxazole. Participants who are allergic to only one of these antibiotics are allowed to enroll
• Concurrent treatment with anti -Tumor necrosis factor (TNF) alpha therapies, systemic corticosteroids (prednisone dose \>10 mg per day or equivalent) or other immune suppressive drugs within the 2 weeks prior to Screening. Steroids that are topical, inhaled, nasal (spray), or ophthalmic solution are permitted

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (6)

Unknown Facility

San Francisco, California, United States

Location

Unknown Facility

Baltimore, Maryland, United States

Location

Unknown Facility

St Louis, Missouri, United States

Location

Unknown Facility

Nashville, Tennessee, United States

Location

Unknown Facility

Houston, Texas, United States

Location

Unknown Facility

Madison, Wisconsin, United States

Location

Related Publications (2)

• Le DT, Dubenksy TW Jr, Brockstedt DG. Clinical development of Listeria monocytogenes-based immunotherapies. Semin Oncol. 2012 Jun;39(3):311-22. doi: 10.1053/j.seminoncol.2012.02.008.

  PMID: 22595054 BACKGROUND

• Brockstedt DG, Giedlin MA, Leong ML, Bahjat KS, Gao Y, Luckett W, Liu W, Cook DN, Portnoy DA, Dubensky TW Jr. Listeria-based cancer vaccines that segregate immunogenicity from toxicity. Proc Natl Acad Sci U S A. 2004 Sep 21;101(38):13832-7. doi: 10.1073/pnas.0406035101. Epub 2004 Sep 13.

  PMID: 15365184 BACKGROUND

MeSH Terms

Conditions

Prostatic Neoplasms, Castration-Resistant

Condition Hierarchy (Ancestors)

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2015
• First Posted: December 9, 2015
• Study Start: December 10, 2015
• Primary Completion: July 3, 2018
• Study Completion: July 3, 2018
• Last Updated: February 3, 2025

Record last verified: 2025-01

Locations

US (6)