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

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.

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