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.

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

Prostatic Neoplasms

Castration-Resistant Prostatic Cancer

Prostatic Neoplasms, Castration-Resistant

Genitourinary Cancer

Prostate Neoplasms

Advanced Solid Tumors

Cancer

Advanced Solid Malignancies

Advanced Solid Tumor

Solid Tumor, Adult

Neoplasms

Adenocarcinoma

Advanced Stage Solid Tumors

JNJ-78278343

JNJ-95298177

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

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.

High grade hematologic or non-hematologic toxicities with exceptions and/or toxicities
leading to treatment discontinuation will be regarded as DLT.

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).

PSA response rate is defined as the percentage of participants with a decline of PSA of
50% or more from baseline.

rPFS is defined as the time from the date of first dose of JNJ-78278343 or JNJ-95298177
until the date of radiographic disease progression or death, whichever comes first.

TTR is defined for the responders as the time from the date of first dose of any study
treatment to the date of first documented response.

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.

Serum samples will be analyzed to determine concentrations of JNJ-78278343.

Serum samples will be analyzed to determine concentrations of JNJ-95298177 (including
ADC, total antibody and payload pAF-AS269).

Serum samples will be analyzed for the detection of anti-JNJ-78278343 antibodies using a
validated assay method.

Serum samples will be analyzed for the detection of anti-JNJ-95298177 antibodies using a
validated assay method.

Participants will receive JNJ-78278343 in combination with JNJ-95298177 in a dose
de-escalation schedule in accordance with the Bayesian Optimal Interval Design (BOIN)
design to determine the recommended phase 2 combination dose (RP2CD) regimen.

Participants will receive JNJ-78278343 in combination with JNJ-95298177 at the RP2CD as
determined in Part 1 of the study to confirm the safety and anti-tumor activity.

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

Trials at a glance

Trials at a glance

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

Outcome measures

Primary outcome measures

Secondary outcome measures