The purpose of this study is to identify the recommended phase 2 combination dose (RP2CD) of Pasritamig in combination with JNJ-86974680 in Part 1 (Dose finding) of the study and to determine how safe and tolerable the RP2CD is for treatment of participants with advanced prostate cancer in Part 2 (Dose expansion) of study.
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
Metastatic castration-resistant prostate cancer (mCRPC) that is metastatic either to bone, any lymph node, or both without clear evidence of metastasis to visceral organs. Local-regional invasion (rectum, bladder) and bone disease with soft tissue component can be included
Prior orchiectomy or medical castration (for example, 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)
Prostate-specific antigen (PSA) greater than or equal to (>=) 2 nanograms per milliliters (ng/mL) at screening
Toxicity related to prior anticancer therapy that has not returned to grade less than or equal to (<=) 1 or baseline levels (except for alopecia, neuropathy [Grade 2] and vitiligo)
Known allergies, hypersensitivity, or intolerance to any of the components (for example, excipients) of pasritamig or JNJ-86974680
Active infection or condition that requires treatment with systemic antibiotics within 7 days prior to the first dose of study treatment. Antibiotic or antiviral prophylaxis is allowed
Have leptomeningeal disease or brain metastases, except participants with definitively, locally treated brain metastases that are clinically stable and asymptomatic >2 weeks, and who are off corticosteroid treatment for at least 2 weeks prior to first dose of study treatment
Sequential
Pasritamig
DrugPasritamig will be administered intravenously.
JNJ-86974680
DrugJNJ-86974680 will be administered orally.
Number of Participants With Adverse Events (AEs) by Severity
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event. Cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines and ocular events will be graded using the alternative scale provided in the protocol.
Part 1: Number of Participants With Dose-Limiting Toxicity (DLT)
High grade hematologic or non-hematologic toxicities with exceptions and/or toxicities leading to treatment discontinuation will be regarded as DLT.
Objective Response Rate (ORR)
ORR is defined as the percentage of participants who have a partial response (PR) or better according to the response evaluation criteria in solid tumors (RECIST) version 1.1 response criteria without evidence of bone progression according to prostate cancer working group 3 (PCWG3).
Prostate-Specific Antigen (PSA) Response Rate
PSA response rate is defined as the percentage of participants with a decline of PSA of 50% or more from baseline.
Duration of Response (DOR)
DOR will be calculated among responders (PR or better) from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the PCWG3 or RECIST version 1.1 response criteria, or death due to any cause, whichever occurs first.
Radiographic Progression-Free Survival (rPFS)
rPFS is defined as the time from the date of first dose of pasritamig or JNJ-86974680 until the date of radiographic disease progression or death, whichever comes first.
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