The purpose of Parts 1, 2A, and 2B of the study is to determine the recommended regimen for Phase 2 (RP2Rs) of combination of JNJ-87189401 with JNJ-78278343 and the purpose of Part 2C of this study is to determine how safe the RP2R(s) of the combination of JNJ-87189401 and JNJ-78278343 is, with or without apalutamide. Part 3 of this study evaluates the safety of the triplet combination of JNJ-87189401 and JNJ-78278343 with standard of care (SOC) lutetium Lu-177 vipivotide tetraxetan. Part 4 of this study further evaluates the safety of the triplet combination of JNJ-87189401 and JNJ-78278343 with JNJ-101556143 in participants with advanced prostate cancer.

A Study of JNJ-87189401 Combined With JNJ-78278343 for Advanced Prostate Cancer

Prostatic Neoplasms

Castration-Resistant Prostatic Cancer

Prostatic Neoplasms, Castration-Resistant

Genitourinary Cancer

Advanced Solid Tumors

Prostate Neoplasms

Cancer

Advanced Solid Malignancies

Advanced Solid Tumor

Solid Tumor, Adult

Neoplasms

Adenocarcinoma

Advanced Stage Solid Tumors

Apalutamide

JNJ-78278343

JNJ-87189401

JNJ-101556143

Lutetium Lu-177 Vipivotide Tetraxetan

A Phase 1 Study of JNJ-87189401 (PSMA-CD28 Bispecific Antibody) Combined With JNJ-78278343 (KLK2-CD3 Bispecific Antibody) for Advanced Prostate Cancer

DLTs are specific adverse events (AEs) and are defined as any of the following: high grade non-hematologic toxicity or hematologic toxicity.

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 with the exception of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome events, which will be graded by American Society for Transplantation and Cellular Therapy (ASTCT) guidelines. 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.

Serum samples will be analyzed to determine concentrations of JNJ-87189401 and JNJ-78278343.

Plasma samples will be analyzed to determine concentrations of JNJ-101556143.

Number of participants with antibodies to JNJ-87189401 and JNJ-78278343 will be reported.

ORR is defined as the proportion of participants who have a partial response (PR) or better according to response evaluation criteria in solid tumors (RECIST) version 1.1 without evidence of bone progression according to Prostate Cancer Clinical Trials Working Group 3 (PCWG3).

rPFS is defined time from the date of first dose of study drug until the date of objective disease progression or death, whichever comes first.

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

DOR is defined for participants who achieved response (PR or better) as the time between the date of initial documentation of response (PR or better) to the date of first documented evidence of progressive disease, as defined in the PCWG3, or death due to any cause, whichever occurs first.

Participants will receive JNJ-78278343 + JNJ-87189401 escalated sequentially in Part 1 to select a recommended Phase 2 regimen (RP2R).

Participants with different disease settings in Parts 2A and 2B will receive JNJ-78278343+JNJ-87189401 at the RP2R selected in Part 1. Participants in Part 2C will receive apalutamide plus continued treatment with JNJ-87189401+JNJ-78278343 doublet.

Participants will receive JNJ-78278343 + JNJ-87189401 at one or more RP2R (s) selected in Part 1 along with standard of care (SOC) treatment with lutetium Lu-177 vipivotide tetraxetan. Dosing of JNJ-78278343+JNJ-87189401 will be escalated sequentially, as per study evaluation team (SET) decision.

Participants will receive JNJ-78278343 + JNJ-87189401 at one or more RP2R (s) along with JNJ-101556143. Dosing of JNJ-78278343+JNJ-87189401 along with JNJ-101556143 will be escalated sequentially to determine the RP2R of the combinations.

The purpose of the study is to determine the recommended regimen for Phase 2 (RP2Rs) of
combination of JNJ-87189401 with JNJ-78278343 (Part 1: dose escalation) and further
evaluate the safety at RP2Rs (Part 2: dose expansion) in participants with advanced
prostate cancer.

A Study of JNJ-87189401 Plus JNJ-78278343 for Advanced Prostate Cancer

University of Colorado Anschutz Medical Campus

Herbert Irving Comprehensive Cancer Center Columbia University Medical Center

South Texas Accelerated Research Therapeutics, LLC (START)

Centre Leon Berard

Institut Gustave Roussy

DLTs are specific adverse events (AEs) and are defined as any of the following: high
grade non-hematologic toxicity or hematologic toxicity.

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 with the exception of cytokine release syndrome (CRS) and immune effector
cell-associated neurotoxicity syndrome events, which will be graded by American Society
for Transplantation and Cellular Therapy (ASTCT) guidelines. 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.

Serum samples will be analyzed to determine concentrations of JNJ-87189401.

ORR is defined as the proportion of participants who have a partial response (PR) or
better according to response evaluation criteria in solid tumors (RECIST) version 1.1
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 confirmed decline
of PSA of 50 percent (%) or more from baseline.

DOR is defined for participants who achieved response (PR or better) as the time between
the date of initial documentation of response (PR or better) to the date of first
documented evidence of progressive disease, as defined in the PCWG3, or death due to any
cause, whichever occurs first.

Participants will receive JNJ-78278343+JNJ-87189401 escalated sequentially in Part 1 to
select a recommended Phase 2 regimen (RP2R). Participants will receive the combination
treatment at the RP2R in Part 2 (dose expansion).

A Study of JNJ-87189401 Combined With JNJ-78278343 for Advanced Prostate Cancer

Trials at a glance

Trials at a glance

A Study of JNJ-87189401 Combined With JNJ-78278343 for Advanced Prostate Cancer

Outcome measures

Primary outcome measures

Secondary outcome measures