JNJ-69086420 for Prostate Cancer

Recruiting at 8 trial locations

Overseen By Study Contact

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Janssen Research & Development, LLC

Must be taking: GnRH analogs

Must not be taking: Chemotherapy, PARP inhibitors

Disqualifiers: Myelodysplastic syndrome, Leukemia, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

247 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine the recommended Phase 2 dose(s) (RP2D\[s\]) of JNJ-69086420 in Part 1 (Dose Escalation), to determine safety and preliminary signs of clinical activity at the RP2D(s) in Part 2 (Dose Expansion), to determine safety of JNJ-69086420 at the RP2D(s) as a combination therapy in Part 3 (combination therapy) and to determine safety of JNJ-69086420 at the RP2D(s) in participants with metastatic hormone-sensitive prostate cancer (mHSPC) in Part 4.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it does mention that certain treatments must be completed a specific number of days before starting the study drug. For example, novel androgen axis drugs must be stopped at least 14 days before, and some other treatments must be completed more than 30 days before the first dose.

What makes the drug JNJ-69086420 unique for treating prostate cancer?

JNJ-69086420 is unique because it is a next-generation androgen receptor antagonist designed to overcome resistance seen in current treatments by targeting both wild-type and mutated androgen receptors, which are common in advanced prostate cancer. ^{1 2 3 4 5}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for men with advanced prostate cancer who have already tried at least one androgen receptor therapy, like abiraterone or enzalutamide. They should be relatively healthy otherwise, with good organ function and a performance status showing they can handle daily activities well. Men who've had certain radioactive treatments or have blood disorders, active hepatitis, or allergies to the study drug can't join.

Inclusion Criteria

I stopped any prostate cancer treatments at least 2 weeks before starting the study drug.

My prostate cancer is advanced, resistant to hormone therapy, and confirmed as adenocarcinoma.

I am fully active or can carry out light work.

Exclusion Criteria

I have previously received treatment with radium Xofigo, strontium, samarium therapy, or radioconjugate therapy.

I have an active or chronic hepatitis B or C infection.

Side effects from my previous cancer treatments are mild or gone, except for hair loss, scar tissue from radiation, or nerve pain.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants will receive JNJ-69086420 with one or multiple doses. The dose levels will be escalated based on the dose limiting toxicities (DLT) evaluation by Study Evaluation Team (SET) until the recommended Phase 2 Dose (RP2D) has been identified.

Up to 2 years and 4 months

Dose Expansion

Participants in one or more cohorts will receive JNJ-69086420 at the RP2D(s) determined in Part 1.

Up to 2 years and 4 months

Combination Therapy

Participants will receive JNJ-69086420 at the determined RP2D(s) and fixed dose of JNJ-78278343.

Up to 2 years and 4 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• JNJ-69086420

Trial Overview The trial is testing JNJ-69086420, a new medication linked to a radioactive substance that targets prostate cancer cells. The first part of the study finds the best dose to use while checking safety. The second part sees how well it works at that dose and monitors any side effects.

Participant Groups

Group I: Part 4: HSPC Expansion Experimental Treatment 2 Interventions

Participants with HSPC will receive JNJ-69086420 at the RP2D(s) in Part 4(a), and JNJ-69086420 following stereotactic body radiation therapy in Part 4(b).

Group II: Part 3: Combination Therapy Experimental Treatment 2 Interventions

Participants will receive JNJ-69086420 at the determined RP2D(s) and fixed dose of JNJ-78278343.

Group III: Part 2: Dose Expansion Experimental Treatment 1 Intervention

Participants in one or more cohorts will receive JNJ-69086420 at the RP2D(s) determined in Part 1.

Group IV: Part 1: Dose Escalation Experimental Treatment 1 Intervention

Participants will receive JNJ-69086420 with one or multiple doses. The dose levels will be escalated based on the dose limiting toxicities (DLT) evaluation by Study Evaluation Team (SET) until the recommended Phase 2 Dose (RP2D) has been identified.

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

JNJ-26146900 is a nonsteroidal androgen receptor antagonist that effectively reduces prostate weight and tumor growth in rat models, showing similar potency to the established drug bicalutamide.

In addition to its anti-cancer effects, JNJ-26146900 significantly prevents bone loss and maintains lean body mass in orchidectomized rats, suggesting potential anabolic benefits for bone and muscle health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A selective androgen receptor modulator that reduces prostate tumor size and prevents orchidectomy-induced bone loss in rats. Allan, G., Lai, MT., Sbriscia, T., et al.[2019]

Chronic treatment with the broad-spectrum AR antagonist JNJ-pan-AR can lead to resistance in prostate cancer cells, with specific enzymes like AKR1C3 identified as key drivers of this resistance.

Targeting AKR1C3 may enhance the effectiveness of antiandrogens and help prevent disease progression in castration-resistant prostate cancer (CRPC), suggesting a potential new therapeutic strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AKR1C3 mediates pan-AR antagonist resistance in castration-resistant prostate cancer. Hertzog, JR., Zhang, Z., Bignan, G., et al.[2021]

JJ-450 is a novel androgen receptor antagonist that effectively inhibits both wild-type and enzalutamide-resistant ARF876L mutant activity in prostate cancer cells, unlike enzalutamide which fails to inhibit the mutant.

In laboratory tests, JJ-450 not only blocked the proliferation of prostate cancer cells expressing the ARF876L mutation but also prevented its nuclear translocation, suggesting it could be a promising treatment for castration-resistant prostate cancer that has become resistant to enzalutamide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel androgen receptor antagonist JJ-450 inhibits enzalutamide-resistant mutant ARF876L nuclear import and function. Wu, Z., Wang, K., Yang, Z., et al.[2021]

The novel compound (+)-JJ-74-138 has been identified as a more potent inhibitor of androgen receptor (AR) activity in enzalutamide-resistant prostate cancer cells compared to its predecessor JJ-450, showing promise for treating patients with resistant forms of the disease.

(+)-JJ-74-138 effectively inhibits the expression of castration-resistant PSA and reduces AR levels in the nucleus, demonstrating its potential as a noncompetitive AR antagonist that can suppress tumor growth in xenograft models of prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

(+)-JJ-74-138 is a Novel Noncompetitive Androgen Receptor Antagonist. Cole, RN., Chen, W., Pascal, LE., et al.[2022]

JNJ-63576253 is a newly discovered next-generation androgen receptor (AR) pathway inhibitor that effectively blocks AR signaling in prostate cancer models, addressing resistance mechanisms seen with current treatments.

This drug is being developed as a clinical candidate specifically for patients with metastatic castration-resistant prostate cancer (mCRPC) who do not respond to or are progressing on existing second-generation AR-targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery of JNJ-63576253, a Next-Generation Androgen Receptor Antagonist Active Against Wild-Type and Clinically Relevant Ligand Binding Domain Mutations in Metastatic Castration-Resistant Prostate Cancer. Branch, JR., Bush, TL., Pande, V., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

A selective androgen receptor modulator that reduces prostate tumor size and prevents orchidectomy-induced bone loss in rats. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

AKR1C3 mediates pan-AR antagonist resistance in castration-resistant prostate cancer. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

A novel androgen receptor antagonist JJ-450 inhibits enzalutamide-resistant mutant ARF876L nuclear import and function. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

(+)-JJ-74-138 is a Novel Noncompetitive Androgen Receptor Antagonist. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Discovery of JNJ-63576253, a Next-Generation Androgen Receptor Antagonist Active Against Wild-Type and Clinically Relevant Ligand Binding Domain Mutations in Metastatic Castration-Resistant Prostate Cancer. [2021]