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

NCT ID: NCT02625857

Last Updated: 2025-02-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-10
• Study Completion Date: 2018-07-03

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 Description

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.

Conditions

Prostatic Neoplasms, Castration-Resistant

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose Cohort 1A and 1B

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

Group Type: EXPERIMENTAL

JNJ-64041809 (Cohort 1A and 1B)

Intervention Type: 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 2A and 2B

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

Group Type: EXPERIMENTAL

JNJ-64041809 (Cohort 2A and 2B)

Intervention Type: BIOLOGICAL

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

Interventions

JNJ-64041809 (Cohort 1A and 1B)

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).

Intervention Type: BIOLOGICAL

JNJ-64041809 (Cohort 2A and 2B)

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

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 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)

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

San Francisco, California, United States

Baltimore, Maryland, United States

St Louis, Missouri, United States

Nashville, Tennessee, United States

Houston, Texas, United States

Madison, Wisconsin, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 22595054 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15365184 (View on PubMed)

Other Identifiers

64041809PCR1001

Identifier Type: OTHER

Identifier Source: secondary_id

CR107668

Identifier Type: -

Identifier Source: org_study_id