JNJ-69086420 for Prostate Cancer

Recruiting at 12 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

177 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called JNJ-69086420 for prostate cancer. Researchers aim to determine the right dose, assess safety, and evaluate its effectiveness, particularly in patients with metastatic hormone-sensitive prostate cancer. The study includes several parts, exploring different combinations with other treatments. This trial may suit individuals with prostate cancer that has spread despite hormone therapy, especially if they have tried other treatments like abiraterone or enzalutamide. 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 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.

Is there any evidence suggesting that JNJ-69086420 is likely to be safe for humans?

Research has shown that JNJ-69086420, a new type of targeted radiotherapy, has been generally well-tolerated in early studies. This treatment uses a special protein to deliver a tiny, high-energy particle directly to prostate cancer cells. Most patients in these studies did not experience severe side effects, and the treatment showed promise in controlling cancer. However, since these findings are preliminary, side effects could still occur as more people try the treatment. Prospective trial participants should discuss any potential risks with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for prostate cancer?

Unlike the standard treatments for prostate cancer, which often include hormone therapy, chemotherapy, or surgery, JNJ-69086420 introduces a new approach by potentially targeting cancer cells differently. Researchers are particularly excited about JNJ-69086420 because it uses a novel mechanism that could work where traditional treatments may not, offering a new hope for patients. Additionally, this treatment is being tested in combination with other therapies and with radiation, which might enhance its effectiveness and provide more comprehensive cancer control. Overall, JNJ-69086420 represents an innovative shift in tackling prostate cancer, aiming to improve outcomes for patients.

What evidence suggests that JNJ-69086420 might be an effective treatment for prostate cancer?

Research has shown that JNJ-69086420, which participants in this trial may receive, may help treat prostate cancer. In an earlier study, 28.1% of patients had their disease under control after six months. Additionally, 45.6% of participants experienced a significant decrease in prostate-specific antigen (PSA) levels, a marker used to monitor prostate cancer. Early results suggest this treatment might provide lasting benefits for some individuals with advanced prostate cancer. JNJ-69086420 delivers radiation directly to cancer cells, potentially slowing tumor growth. ^{1 2 3 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?

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.

I am fully active or can carry out light work.

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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

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]

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]

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]

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]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.5010

A phase 1 study of JNJ-69086420 (JNJ-6420), an actinium- ... Abstract ; Complete response, 1 (4.2) ; Partial response, 2 (8.3) ; Disease control rate at 6 months · 16 (28.1) ; PSA50, 26 (45.6).

2. targetedonc.com targetedonc.com/view/jnj-6420-shows-early-signs-of-efficacy-with-safety-considerations-in-mcrpc

JNJ-6420 Shows Early Signs of Efficacy With Safety ... A new radioligand therapy, JNJ-6420, shows promise in treating metastatic castration-resistant prostate cancer with deep and lasting responses after just 1-2 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04644770

A Study of JNJ-69086420, an Actinium-225-Labeled ... 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 ...

4. jnm.snmjournals.org jnm.snmjournals.org/content/early/2025/10/03/jnumed.125.270940

α-Therapy and Combination Strategies to Overcome ... A phase 1 study of JNJ-69086420 (JNJ-6420), an actinium-225 (225Ac)-labeled antibody targeting human kallikrein 2 (hK2), for metastatic ...

5. mayo.edu mayo.edu/research/clinical-trials/cls-20588822?&p=1

A Study of JNJ-69086420, an Actinium-225-Labeled ... A Study of JNJ-69086420, an Actinium-225-Labeled Antibody Targeting Human Kallikrein-2 (hK2) for Advanced Prostate Cancer.

6. urotoday.com urotoday.com/conference-highlights/asco-2024/asco-2024-prostate-cancer/152617-asco-2024-a-phase-1-study-of-jnj-69086420-jnj-6420-an-actinium-225-225ac-labeled-antibody-targeting-human-kallikrein-2-for-mcrpc.html

ASCO 2024: A Phase 1 Study of JNJ-69086420 (JNJ-6420 ... JNJ-6420 is a first-in-class anti-human kallikrein 2 antibody-based targeted radiotherapy delivering 225 Ac, a high-energy short-range alpha-particle emitter, ...

7. jnjmedicalconnect.com jnjmedicalconnect.com/media/attestation/congresses/oncology/2024/am/a-phase-1-study-of-jnj69086420-an-225aclabeled-antibody-targeting-human-kallikrein-2-to-treat-metast.pdf

A phase 1 study of JNJ-69086420, an A phase 1 study of JNJ-69086420, an. 225Ac-labeled antibody targeting human kallikrein 2 to treat metastatic castration- resistant prostate cancer. Michael J ...