A Study of JNJ-78278343, a T-Cell-Redirecting Agent Targeting Human Kallikrein 2 (KLK2), for Advanced Prostate Cancer

The purpose of this study is to determine the recommended phase 2 dose(s) (RP2Ds) of JNJ-78278343 in Part 1 (Dose Escalation) and the safety at the RP2Ds in Part 2 (Dose Expansion).

Inclusion Criteria: * Confirmed adenocarcinoma of the prostate which has spread to other body parts * Part 1: Prior treatment with at least 1 prior novel androgen receptor (AR)-targeted therapy or chemotherapy * Measurable or evaluable disease * Concurrent use of any other anticancer treatment must be discontinued for at least 2 weeks before the first dose of study drug * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Prior surgical removal of testicles; or, for participants who have not undergone surgical removal of testicles, must be receiving ongoing androgen deprivation therapy (ADT) with a gonadotropin releasing hormone analog Exclusion Criteria: Disease conditions * Active central nervous system (CNS) involvement * Toxicity related to prior anticancer therapy has not adequately recovered Prior/Concomitant Therapy * Prior treatment with human kallikrein (KLK) 2-targeted therapy * Received, or are receiving, medications that suppress the immune system within 3 days prior to the first dose of study drug * Received or plans to receive any live, attenuated vaccine within 4 weeks prior to the first dose of study drug Prior/Concurrent Medical Conditions * Diagnosis of cancer other than prostate cancer within 2 years prior to the first dose of study drug * Solid organ or bone marrow transplantation * Major clotting diseases within one month prior to the first dose of study drug * Active autoimmune disease within 12 months prior to the first dose of study drug * Active infection * Major diseases of heart and blood vessels within 6 months prior to the first dose of study drug * Clinically significant lung diseases * Active or chronic hepatitis B or hepatitis C infection * Known positive test result for human immunodeficiency virus (unless stable on antiretroviral therapy with undetectable viral load) * Any serious underlying medical conditions or other issue that would impair the ability of the participant to receive or tolerate the planned treatment