JNJ-80038114 for Prostate Cancer

Recruiting at 7 trial locations

Overseen By Study Contact

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Janssen Research & Development, LLC

Must not be taking: Anticancer therapy

Disqualifiers: Brain metastasis, Seizure history, others

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

Compensation: Varies

Number of Visits: Unknown

39 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial aims to find the best amount of a new drug, JNJ-80038114, and ensure it is safe for people who might benefit from it.

Will I have to stop taking my current medications?

The trial requires that you stop any current anticancer therapy before participating.

What data supports the effectiveness of the drug JNJ-80038114 for prostate cancer?

Research on similar drugs, like JNJ-26146900, shows they can reduce prostate tumor size in animal models and prevent bone loss after castration, which is promising for treating prostate cancer. Additionally, other drugs in the same class have been effective against resistant forms of prostate cancer, suggesting potential for JNJ-80038114. ^{1 2 3 4 5}

What safety data exists for JNJ-80038114 or similar treatments?

ABT-494, a selective JAK1 inhibitor like JNJ-80038114, has been studied for safety and tolerability in healthy volunteers and people with rheumatoid arthritis, suggesting it may have a good safety profile compared to non-selective JAK inhibitors. ^{6 7 8 9 10}

How is the drug JNJ-80038114 different from other prostate cancer treatments?

JNJ-80038114 is unique because it is a selective androgen receptor modulator (SARM) that targets androgen receptors in a tissue-specific manner, potentially reducing prostate tumor size while minimizing side effects like bone loss, which is a common issue with other treatments. ^{1 2 3 11 12}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

Men with advanced prostate cancer who have already tried at least one treatment can join this trial. They should be in good physical shape (able to perform daily activities without much help) and have their major organs working well. Participants must agree to use effective birth control, and they cannot have brain metastases, a history of seizures, severe ongoing side effects from previous cancer treatments, or allergies to the study drug.

Inclusion Criteria

I have had at least one treatment for metastatic castration-resistant prostate cancer.

My prostate cancer has spread and does not respond to hormone therapy.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I have brain metastasis or a history of seizures.

I am allergic to JNJ-80038114 or its ingredients.

I do not have serious infections or major heart, lung, or other health issues.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive JNJ-80038114 with dose levels escalated based on dose limiting toxicities evaluation

Up to 2 Years 6 Months

Dose Expansion

Participants receive JNJ-80038114 at the recommended Phase 2 dose determined in Part 1

Up to 2 Years 6 Months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• JNJ-80038114

Trial Overview The trial is testing JNJ-80038114's safety and optimal dosing for men with advanced prostate cancer. The first part will find the best dose by gradually increasing it among different groups. In the second part, more people will take this found dose to see how safe it is.

Participant Groups

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

Participants will receive JNJ-80038114 at the recommended Phase 2 dose (RP2D) determined in Part 1.

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

Participants will receive JNJ-80038114. The dose levels will be escalated based on the dose limiting toxicities (DLTs) evaluation by the study evaluation team (SET).

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

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]

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]

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]

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]

Docetaxel is the first-line treatment for metastatic castration-resistant prostate cancer, but its effectiveness is often limited by dose-limiting toxicities such as neutropenia and neurotoxicity.

Research identified Janus kinase 1 (JAK1) as a promising target to enhance docetaxel sensitivity, showing that JAK1 inhibitors can synergize with docetaxel to increase cancer cell apoptosis, particularly in androgen receptor-negative prostate cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of Janus Kinase 1 synergizes docetaxel sensitivity in prostate cancer cells. Nalairndran, G., Chung, I., Abdul Razack, AH., et al.[2022]

ABT-494, a selective JAK 1 inhibitor, demonstrated favorable pharmacokinetics and safety in healthy subjects and those with rheumatoid arthritis, with mild to moderate side effects and no significant drug interactions with methotrexate.

The study involved 56 healthy participants for single dosing and 44 for multiple dosing, showing that ABT-494 had a manageable elimination half-life and dose-proportional exposure, supporting its potential for further testing in phase IIb trials for rheumatoid arthritis and Crohn's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, Safety and Tolerability of ABT-494, a Novel Selective JAK 1 Inhibitor, in Healthy Volunteers and Subjects with Rheumatoid Arthritis. Mohamed, MF., Camp, HS., Jiang, P., et al.[2018]

Tofacitinib, a JAK1-3 inhibitor approved by the FDA, has been shown to inhibit the histone kinase PRK1 in both laboratory and cellular settings, suggesting its potential as a treatment for prostate cancer.

Through structure-activity relationship studies, researchers identified a more potent and selective PRK1 inhibitor than tofacitinib, along with two selectivity hotspots that could guide the development of future PRK1-targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib and analogs as inhibitors of the histone kinase PRK1 (PKN1). Ostrovskyi, D., Rumpf, T., Eib, J., et al.[2018]

PCK3145 was found to be safe and well tolerated in 16 patients with metastatic hormone-refractory prostate cancer, with the most common side effects being pain and nausea, and only one serious adverse event (grade 4 cardiac arrhythmia) at the highest dose.

While no significant PSA responses were observed, PCK3145 showed potential efficacy by stabilizing disease in 10 patients and significantly reducing MMP-9 levels, suggesting it may help regulate metastatic tumor growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of PCK3145, a synthetic peptide derived from prostate secretory protein 94 (PSP94) in metastatic hormone-refractory prostate cancer. Hawkins, RE., Daigneault, L., Cowan, R., et al.[2022]

References

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

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

2. 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]

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. Greece pubmed.ncbi.nlm.nih.gov

Novel strategies in the treatment of castration-resistant prostate cancer (Review). [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]

6. England pubmed.ncbi.nlm.nih.gov

Inhibition of Janus Kinase 1 synergizes docetaxel sensitivity in prostate cancer cells. [2022]

7. England pubmed.ncbi.nlm.nih.gov

AJM300, a novel oral antagonist of α4-integrin, sustains an increase in circulating lymphocytes: A randomised controlled trial in healthy male subjects. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Genetic evidence supporting a causal role of Janus kinase 2 in prostate cancer: a Mendelian randomization study. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, Safety and Tolerability of ABT-494, a Novel Selective JAK 1 Inhibitor, in Healthy Volunteers and Subjects with Rheumatoid Arthritis. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Tofacitinib and analogs as inhibitors of the histone kinase PRK1 (PKN1). [2018]

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

A selective androgen receptor modulator with minimal prostate hypertrophic activity enhances lean body mass in male rats and stimulates sexual behavior in female rats. [2021]

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

Safety and tolerability of PCK3145, a synthetic peptide derived from prostate secretory protein 94 (PSP94) in metastatic hormone-refractory prostate cancer. [2022]