RecruitingPhase 1NCT07082920

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

A Phase 1b Study of JNJ-78278343, a T-cell Redirecting Agent Targeting Human Kallikrein 2 (KLK2), in Combination With JNJ-95298177, an Antibody Drug Conjugate Targeting Prostate Specific Membrane Antigen, for Prostate Cancer

Sponsor

Janssen Research & Development, LLC

Enrollment

140 participants

Start Date

Jul 7, 2025

Study Type

INTERVENTIONAL

Conditions

Prostatic Neoplasms

Summary

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 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.

Eligibility

Sex: MALEMin Age: 18 Years

Inclusion Criteria6

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 Criteria11

Toxicity related to prior anticancer therapy that has not returned to grade less than or equal to (\<=) 1 or baseline levels (except for alopecia and vitiligo)
Known allergies, hypersensitivity, or intolerance to any of the components (e.g., excipients) of JNJ-78278343 or JNJ-95298177
Participants with leptomeningeal disease or brain metastases, with the exception of participants with definitively, locally treated brain metastases that are clinically stable and asymptomatic greater than (\>) 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