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

A Phase 1 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).

Study Overview

• Status: Recruiting
• Conditions: Prostatic Neoplasms
• Intervention / Treatment: Drug: JNJ-78278343

Detailed Description

JNJ-78278343 is a humanized immunoglobulin (Ig)G1-based bispecific antibody designed to direct T lymphocytes (T cells) to human kallikrein 2 (hK2or KLK2) positive target tumor cells. One arm of JNJ-78278343 binds to the cluster of differentiation (CD)3 receptor complex present on T cells and the other arm binds to KLK2 present on target tumor cells leading to the activation of the T cells and T-cell-mediated lysis of the KLK2 bearing tumor cells. JNJ-78278343 is being developed for the treatment of metastatic castration-resistant prostate cancer (mCRPC). KLK2 expression is highly restricted in normal tissues and highly enriched in prostate adenocarcinoma and its expression is mostly maintained throughout disease progression, making KLK2 an attractive target for therapy. This study will be conducted in 2 phases: a Screening Phase (up to 30 days), a Treatment Phase (start of study drug administration) with an end of treatment (EOT) visit (up to 30 plus 14 days after last dose of study drug or prior to the start of a new anticancer therapy), whichever comes first). The total duration of the study is up to 1 year and 10 months. Safety assessment will include adverse events (AEs) including dose-limiting toxicity (DLT), serious adverse events (SAEs), physical examination, vital signs, electrocardiogram, clinical safety laboratory assessments, Eastern Cooperative Oncology Group (ECOG) performance status, and neurologic examination.

• Study Type: Interventional
• Enrollment (Estimated): 260
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Study Contact; Phone Number: 844-434-4210; Email: Participate-In-This-Study@its.jnj.com

Study Locations

• China
  • Beijing, China, 100191
    • Recruiting
    • Peking University Third Hospital
  • Chongqing, China, 400030
    • Recruiting
    • Chongqing University Cancer Hospital
  • Guang Zhou Shi, China, 510710
    • Recruiting
    • Sun Yat-sen University Cancer Center
  • Wen Zhou Shi, China, 325399
    • Recruiting
    • First Affiliated Hospital Of Wenzhou Medical College
• France
  • Lyon Cedex 8, France, 69373
    • Recruiting
    • Centre Leon Berard
  • Marseille, France, 13005
    • Recruiting
    • APHM Hopital Timone
  • Villejuif, France, 94800
    • Recruiting
    • Institut Gustave Roussy
• Japan
  • Yokohama, Japan, 232 0024
    • Recruiting
    • Yokohama City University Medical Center
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Completed
    • Antoni van Leeuwenhoek
  • Rotterdam, Netherlands, 3015 GD
    • Recruiting
    • Erasmus MC
• Spain
  • Madrid, Spain, 28040
    • Recruiting
    • Hosp Univ Fund Jimenez Diaz
  • Madrid, Spain, 28050
    • Recruiting
    • Hosp Univ Hm Sanchinarro
  • Málaga, Spain, 29010
    • Recruiting
    • Hosp Virgen de La Victoria
• United States
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center Herbert Irving Pavilion
  • Washington
    • Seattle, Washington, United States, 98195-9472
      • Recruiting
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JNJ-78278343; Participants will receive JNJ-78278343. The dose levels will be escalated based on the dose limiting toxicities (DLT) evaluation by the study evaluation team (SET) in Part 1 (dose escalation). In Part 2 (dose expansion), participants will receive JNJ-78278343 at recommended phase 2 dose (RP2D) as determined in Part 1.	Drug: JNJ-78278343; JNJ-78278343 will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 and 2: Number of Participants With Adverse Events (AEs)	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.	Up to 1 year and 10 months
Part 1 and 2: Number of Participants With AEs by Severity	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.	Up to 1 year and 10 months
Part 1: Number of Participants With Dose-Limiting Toxicity (DLT)	Number of participants with DLT will be reported. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.	Up to 1 year and 10 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Concentration of JNJ-78278343	Serum concentrations of JNJ-78278343 will be determined.	Up to 1 year and 10 months
Systemic Cytokine Concentrations	Cytokine concentrations will be determined for biomarker assessment.	Up to 1 year and 10 months
Serum Prostate Specific Antigen (PSA) Concentration	Serum PSA concentration will be measured.	Up to 1 year and 10 months
Number of Participants With Anti-JNJ-78278343 Antibodies	Serum samples will be analyzed for the detection of anti-JNJ-78278343 antibodies using a validated assay method.	Up to 1 year and 10 months
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).	Up to 1 year and 10 months
PSA Response Rate	PSA response rate is defined as the percentage of participants with a decline of PSA of 50 percent (%) or more from baseline. The maximum reduction from baseline in PSA will also be calculated during the treatment.	Up to 1 year and 10 months
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.	Up to 1 year and 10 months
Radiographic Progression-free Survival (rPFS)	rPFS is defined as time from the date of first dose of JNJ-78278343 until the date of objective disease progression or death, whichever comes first.	Up to 1 year and 10 months

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): July 13, 2021
• Primary Completion (Estimated): February 13, 2026
• Study Completion (Estimated): February 16, 2026

Study Registration Dates

• First Submitted: May 20, 2021
• First Submitted That Met QC Criteria: May 20, 2021
• First Posted (Actual): May 24, 2021

Study Record Updates

• Last Update Posted (Estimated): January 10, 2025
• Last Update Submitted That Met QC Criteria: January 9, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Advanced prostate cancer; Metastatic castration-resistant prostate cancer (mCRPC)
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: CR108958; 2020-005970-83 (EudraCT Number); 78278343PCR1001 (Other Identifier: Janssen Research & Development, LLC); 2023-506585-31-00 (Registry Identifier: EUCT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes