JNJ-80038114 for Prostate Cancer

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, JNJ-80038114 (an experimental drug), for metastatic castration-resistant prostate cancer. The goal is to determine the optimal dose and assess its safety. The trial consists of two parts: the first part tests different dose levels, and the second part uses the best dose identified. This trial may suit individuals who have tried at least one other treatment for this type of cancer and have confirmed prostate cancer. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

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

Is there any evidence suggesting that JNJ-80038114 is likely to be safe for humans?

Research shows that JNJ-80038114, a new treatment for prostate cancer, remains in the early testing stages, so limited safety information is available. However, similar treatments have undergone safety studies. For instance, ABT-494, which resembles JNJ-80038114, proved safe in previous studies, suggesting that JNJ-80038114 might also be well-tolerated. As a Phase 1 trial, the primary goal is to determine the best dose while monitoring for side effects. Participants in this study phase help researchers assess the treatment's safety for future use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for prostate cancer, like hormone therapy and chemotherapy, aim to control the disease by blocking hormones or killing rapidly dividing cells. But JNJ-80038114 works differently, targeting specific pathways in cancer cells that are not addressed by existing therapies. Researchers are excited because this new mechanism of action has the potential to be more precise, potentially reducing side effects and improving outcomes for patients.

What evidence suggests that JNJ-80038114 might be an effective treatment for prostate cancer?

Research on similar drugs, such as JNJ-26146900, has shown promise in reducing prostate tumor size in animal studies. These drugs have also effectively prevented bone loss after castration, a common issue in prostate cancer treatment. JNJ-80038114, the investigational treatment in this trial, belongs to the same group of drugs, called BiTE therapies, designed to help the body's immune system find and destroy cancer cells. Although specific data on JNJ-80038114 in humans is limited, early results from similar treatments suggest it could be effective for advanced prostate cancer. ^{1 2 5 6 7}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05441501

NCT05441501 | A Study of JNJ-80038114 in Participants ... A Study of JNJ-80038114 in Participants With Advanced Stage Prostate Cancer. ClinicalTrials.gov ID NCT05441501. Sponsor Janssen Research & Development, LLC.

2. isrctn.com isrctn.com/ISRCTN16457874

A study of JNJ-80038114 in participants with advanced ... The purpose of this study is to see if a new study drug can be used in future studies for the treatment of prostate cancer.

3. withpower.com withpower.com/trial/phase-1-prostatic-neoplasms-9-2022-fec43

JNJ-80038114 for Prostate Cancer · Info for Participants 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 ...

4. isrctn.com isrctn.com/pdf/16457874

A study of JNJ-80038114 in participants with advanced ... This study will include participants aged 18 years and over with metastatic castration-resistant prostate cancer. What does the study involve?

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11135853/

T-Cell redirecting bispecific antibodies: a review of a novel ... This review will highlight some of most recent developments of BiTE therapies for patients with advanced prostate cancer and the evolving data ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10285603/

Bispecific PSMA antibodies and CAR-T in metastatic ... This review article highlights the biologic rationale for employment of T-cell redirecting therapies for the treatment of prostate cancer, and ...

7. app.trialscreen.org app.trialscreen.org/trials/phase-1-prostatic-neoplasms-jnj-80038114-participants-advanced-stage-prostate-trial-nct05441501

A Study of JNJ-80038114 in Participants With Advanced ... This Interventional study is looking for people with Prostatic Neoplasms in Nashville United States, Freiburg Germany, London United Kingdom ...