A Study of JNJ-78278343 in Combination With JNJ-95298177 for Treatment of Prostate Cancer

About This Trial

This early-stage clinical trial is testing a new combination of experimental drugs to find the safest dose and check for side effects.
It is designed for men with advanced prostate cancer that has spread to other parts of the body and no longer responds to standard hormone treatments.
To join, participants must be well enough to handle daily activities and continue taking their usual hormone-lowering therapy.
Before considering this study, patients should know that because it is in an early testing phase, the primary goal is to evaluate safety rather than cure the cancer, and having received certain recent cancer treatments may prevent you from participating.

More Information

The purpose of this study is to identify the recommended phase 2 combination dose (RP2CD) of JNJ-78278343 in combination with JNJ-95298177 in Part 1 (Dose confirmation) of the study and to determine how safe and tolerable the RP2CD of JNJ-7827834 and JNJ-95298177 with or without JNJ-87189401 is for treatment of participants with metastatic castration-resistant prostate cancer (mCRPC; a stage of prostate cancer where the cancer has spread beyond the prostate and is resistant to hormonal therapy) in Part 2 (Dose expansion) of study.

Who Can Enroll

Age Range: 18 years and older
Gender: Male
Who This Trial is For: This early-stage clinical trial is testing a new combination of experimental drugs to find the safest dose and check for side effects.

Study Details

Start Date: July 7, 2025
Lead Sponsor: Janssen Research & Development, LLC

Full Eligibility Criteria

Inclusion Criteria

Histologically confirmed adenocarcinoma of the prostate. Primary small cell carcinoma, carcinoid tumor, neuroendocrine (NE) carcinoma, or large cell NE carcinoma arising in the prostate are not allowed; however, adenocarcinomas with NE features (for example [e.g.], immunohistochemistry [IHC] with both androgen receptor [AR]- and NE-marker positivity) are allowed
Must have metastatic castration-resistant prostate cancer (mCRPC)
PSA must measure at least 2 nanograms per milliliters (ng/mL) at screening
Measurable or evaluable disease
Prior orchiectomy or medical castration; or, for participants who have not undergone orchiectomy, must be receiving ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) analog (agonist or antagonist) prior to the first dose of study drug and must continue this therapy throughout the treatment phase
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria

Toxicity related to prior anticancer therapy that has not returned to grade less than or equal to () 2 weeks, and who are off corticosteroid treatment for at least 2 weeks prior to first dose of study treatment
Treatment with any anti-cancer or investigational agents within 14 days prior to the first dose of study treatment; specific requirements for certain anti-cancer therapies are as follows:
- Any T-cell redirecting treatment (e.g., CD3-directed bispecific or Chimeric Antigen Receptor T-cell [CAR-T] therapy) within 90 days prior to the first dose of study treatment
- Immune checkpoint inhibitors within 6 weeks prior to the first dose of study treatment
- Radium (Ra) 223 dichloride within 28 days prior to the first dose of study treatment
- Any prior treatment with kallikrein-related peptidase 2 (KLK2)-targeted therapy
- Any prior prostate-specific membrane antigen (PSMA)-targeting therapy (that is [i.e.], participants who received PSMA-targeting radioconjugates are excluded) [Parts 2A and 2B only]. Prior PSMA RLT is allowed in Part 1 and required for Part 2C and Part 2D but last dose must be >3 months prior to the first dose of study treatment
- Any prior antibody drug conjugates (ADCs) with microtubule inhibitor payloads (e.g., auristatins, maytansinoids, tubulysins)
Any serious underlying medical conditions or other issue that would impair the ability of the participant to receive or tolerate the planned treatment at the investigational site to understand the informed consent, or any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant or that could prevent, limit, or confound the protocol-specified assessments