Clinical trial NCT02625857: Safety & Immunogenicity of JNJ-64041809, a Live Attenuated Double-deleted Listeria Immunotherapy, in Participants With Metastatic Castration-resistant Prostate Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Prostatic Neoplasms, Castration-Resistant
Keywords: Prostatic Neoplasms, Castration-Resistant
JNJ-64041809
Listeria monocytogenes
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2015-12-09
Enrollment: 26
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Part 1: Incidence of Dose-limiting-toxicity (DLT)
timeFrame: first 21 days after the first infusion
measure: Part 2: Antigen-specific T-cell Response
timeFrame: up to 1 year
measure: Part 1 and Part 2: Incidence of Adverse Events (AEs)
timeFrame: From signing of informed consent form to 30 days after last dose of study drug
Secondary outcomes:
measure: Part 1 and Part 2: Objective Response Rate (ORR)
timeFrame: Baseline up to 30 days after last dose of study drug
measure: Part 1 and Part 2: Duration of Response (DOR)
timeFrame: Baseline up to 30 days after last dose of study drug
measure: Part 1 and Part 2: Progression-free Survival (PFS)
timeFrame: Baseline up to 30 days after last dose of study drug
measure: Part 1 and Part 2: Time to Prostate Specific Antigen (PSA) progression (TTPP)
timeFrame: Baseline up to 30 days after last dose of study drug
measure: Part 1 and Part 2: Blood Culture Assessment of JNJ-64041809
timeFrame: Periodically during treatment and up to one year after End of Treatment (EOT) visit
measure: Part 1 and Part 2: Shedding Profile of JNJ-64041809 From Cultured Samples of Feces, Urine, and Saliva
timeFrame: During cycle 1 (up to 21 days of treatment period) and at EOT visit (within 30 days after last dose)
Other outcomes:
Locations:
city: San Francisco
country: United States
state: California
city: Baltimore
country: United States
state: Maryland
city: Saint Louis
country: United States
state: Missouri
city: Nashville
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
city: Madison
country: United States
state: Wisconsin
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.