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

Study Status: Suspended
Recruit Status: Suspended
Study Type: Interventional

Official Title: An Open-Label, Phase 1 Study of the Safety and Immunogenicity of JNJ-64041809, a Live Attenuated Listeria Monocytogenes Immunotherapy, in Subjects With Metastatic Castration-resistant Prostate Cancer

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).

Detailed Summary: This is a first-in-human (FIH), Phase 1, open-label, multicenter and 2-part study. The Part 1 of study will be Dose Escalation phase to determine the recommended Phase 2 dose (RP2D) based on safety and pharmacodynamic assessments and Part 2 will be Dose Expansion Phase to evaluate 2 expansion cohorts (Cohort 2A and 2B) after the RP2D for JNJ-64041809 is determined in Part 1. The study will consist of a Screening Period (from signing of informed consent until immediately before the first dose), an open-label Treatment Period (from the first dose of study drug until the End-of-Treatment Visit); and a Post treatment Follow-up Period (after the End-of Treatment Visit until study discontinuation). Participants will be primarily evaluated for RP2D. Participants safety will be evaluated throughout the study.
Sponsor: Janssen Research & Development, LLC

Current Primary Outcome:

• Part 1: Incidence of Dose-limiting-toxicity (DLT) [ Time Frame: first 21 days after the first infusion ]
  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 (%).
• Part 2: Antigen-specific T-cell Response [ Time Frame: up to 1 year ]
  Biomarker studies will be performed to evaluate immune responses to the vaccine after the first intravenous (IV) immunization.
• Part 1 and Part 2: Incidence of Adverse Events (AEs) [ Time Frame: From signing of informed consent form to 30 days after last dose of study drug ]
  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).

Original Primary Outcome:

• Part 1: Incidence of Dose-limiting-toxicity (DLT) [ Time Frame: first 21 days after the first infusion ]
  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 (%).
• Part 2: Antigen-specific T-cell Response [ Time Frame: up to 1 year ]
  Leukapheresis will be performed to evaluate immune responses to the vaccine after an single intravenous (IV) immunization.
• Part 1 and Part 2: Incidence of Adverse Events (AEs) [ Time Frame: From signing of informed consent form to 30 days after last dose of study drug ]
  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).

Current Secondary Outcome:

• Part 1 and Part 2: Objective Response Rate (ORR) [ Time Frame: Baseline up to 30 days after last dose of study drug ]
  Objective response rate is defined as the percentage of participants who achieve complete response (CR) or partial response (PR), as assessed by the investigator.
• Part 1 and Part 2: Duration of Response (DOR) [ Time Frame: Baseline up to 30 days after last dose of study drug ]
  Duration of response will be calculated from the date of initial documentation of a response (CR or PR) to the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death.
• Part 1 and Part 2: Progression-free Survival (PFS) [ Time Frame: Baseline up to 30 days after last dose of study drug ]
  Progression-free survival is defined as the duration from the date of first dose of study drug until the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death, whichever comes first.
• Part 1 and Part 2: Time to Prostate Specific Antigen (PSA) progression (TTPP) [ Time Frame: Baseline up to 30 days after last dose of study drug ]
  Time to PSA progression is measured from the date of first dose of study drug until the date of PSA progression according to the Prostate Cancer Clinical Trials Working Group (PCWG2) criteria.
• Part 1 and Part 2: Blood Culture Assessment of JNJ-64041809 [ Time Frame: Periodically during treatment and up to one year after End of Treatment (EOT) visit ]
  This assessment will include the reporting of surveillance blood cultures (peripherally drawn, and through venous access device [if applicable]) for 1 year after the completion of JNJ-64041809 therapy.
• Part 1 and Part 2: Shedding Profile of JNJ-64041809 From Cultured Samples of Feces, Urine, and Saliva [ Time Frame: During cycle 1 (up to 21 days of treatment period) and at EOT visit (within 30 days after last dose) ]
  The shedding of JNJ-64041809 will be studied in cultures of (1) feces by stool or rectal swab, (2) urine samples, and (3) saliva samples.

Original Secondary Outcome:

• Part 1 and Part 2: Objective Response Rate (ORR) [ Time Frame: Baseline up to 30 days after last dose of study drug ]
  Objective response rate is defined as the percentage of participants who achieve complete response (CR) or partial response (PR), as assessed by the investigator.
• Part 1 and Part 2: Duration of Response (DOR) [ Time Frame: Baseline up to 30 days after last dose of study drug ]
  Duration of response will be calculated from the date of initial documentation of a response (CR or PR) to the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death.
• Part 1 and Part 2: Progression-free Survival (PFS) [ Time Frame: Baseline up to 30 days after last dose of study drug ]
  Progression-free survival is defined as the duration from the date of first dose of study drug until the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death, whichever comes first.
• Part 1 and Part 2: Time to Prostate Specific Antigen (PSA) progression (TTPP) [ Time Frame: Baseline up to 30 days after last dose of study drug ]
  Time to PSA progression is measured from the date of first dose of study drug until the date of PSA progression according to the Prostate Cancer Clinical Trials Working Group (PCWG2) criteria.

Dates:
Date Received: December 7, 2015
Date Started: December 2015
Date Completion: January 2018
Last Updated: January 30, 2017
Last Verified: January 2017