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

Must have received: androgen deprivation therapy (orchiectomy, gonadotropin-releasing hormone (GnRH) analog (agonist or antagonist)) — castration

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

Cannot have received: T-cell redirecting treatment (CD3-directed bispecific, Chimeric Antigen Receptor T-cell (CAR-T) therapy)

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

Cannot have received: immune checkpoint inhibitor

Immune checkpoint inhibitors within 6 weeks prior to the first dose of study treatment

Cannot have received: radium-223 dichloride (radium (Ra) 223 dichloride)

Radium (Ra) 223 dichloride within 28 days prior to the first dose of study treatment

Cannot have received: KLK2-targeted therapy

Any prior treatment with kallikrein-related peptidase 2 (KLK2)-targeted therapy

Cannot have received: PSMA-targeting therapy

Exception: 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

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

Cannot have received: antibody-drug conjugate (auristatins, maytansinoids, tubulysins)

Any prior antibody drug conjugates (ADCs) with microtubule inhibitor payloads (e.g., auristatins, maytansinoids, tubulysins)