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

• ClinicalTrials.gov Identifier: NCT04898634
• Recruitment Status: Recruiting
• First Posted: May 24, 2021
• Last Update Posted: April 24, 2024
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Tracking Information

• First Submitted Date: May 20, 2021
• First Posted Date: May 24, 2021
• Last Update Posted Date: April 24, 2024
• Actual Study Start Date: July 13, 2021
• Estimated Primary Completion Date: November 30, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 29, 2022)

• Part 1 and 2: Number of Participants With Adverse Events (AEs) [ Time Frame: Up to 1 year and 10 months ]
  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.
• Part 1 and 2: Number of Participants With AEs by Severity [ Time Frame: Up to 1 year and 10 months ]
  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.
• Part 1: Number of Participants With Dose-Limiting Toxicity (DLT) [ Time Frame: Up to 1 year and 10 months ]
  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.

Original Primary Outcome Measures (submitted: May 20, 2021)

• Part 1 and 2: Number of Participants With Adverse Events (AEs) [ Time Frame: Up to 1 year and 10 months ]
  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.
• Part 1 and 2: Number of Participants With AEs by Severity [ Time Frame: Up to 1 year and 10 months ]
  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) will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines.
• Part 1: Number of Participants With Dose-Limiting Toxicity (DLT) [ Time Frame: Up to 1 year and 10 months ]
  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.

Current Secondary Outcome Measures (submitted: May 20, 2021)

• Serum Concentration of JNJ-78278343 [ Time Frame: Up to 1 year and 10 months ]
  Serum concentrations of JNJ-78278343 will be determined.
• Systemic Cytokine Concentrations [ Time Frame: Up to 1 year and 10 months ]
  Cytokine concentrations will be determined for biomarker assessment.
• Serum Prostate Specific Antigen (PSA) Concentration [ Time Frame: Up to 1 year and 10 months ]
  Serum PSA concentration will be measured.
• Number of Participants With Anti-JNJ-78278343 Antibodies [ Time Frame: Up to 1 year and 10 months ]
  Serum samples will be analyzed for the detection of anti-JNJ-78278343 antibodies using a validated assay method.
• Objective Response Rate (ORR) [ Time Frame: Up to 1 year and 10 months ]
  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 [ Time Frame: Up to 1 year and 10 months ]
  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.
• Duration of Response (DOR) [ Time Frame: Up to 1 year and 10 months ]
  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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of JNJ-78278343, a T-Cell-Redirecting Agent Targeting Human Kallikrein 2 (KLK2), for Advanced Prostate Cancer
• Official Title: A Phase 1 Study of JNJ-78278343, a T-Cell-Redirecting Agent Targeting Human Kallikrein 2 (KLK2), for Advanced Prostate Cancer
• Brief Summary: 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).
• 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
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Prostatic Neoplasms

Intervention

Drug: JNJ-78278343

JNJ-78278343 will be administered subcutaneously (injection or infusion) or via intravenous infusion.

Study Arms

Experimental: JNJ-78278343

Participants will receive JNJ-78278343 either subcutaneously (SC injection or SC infusion) or intravenous (IV) infusion. 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 either SC or IV at recommended phase 2 dose (RP2D) as determined in Part 1.

Intervention: Drug: JNJ-78278343

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 10, 2023): 165
• Original Estimated Enrollment (submitted: May 20, 2021): 70
• Estimated Study Completion Date: November 15, 2025
• Estimated Primary Completion Date: November 30, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Study Contact; 844-434-4210; Participate-In-This-Study@its.jnj.com

• Listed Location Countries: France, Netherlands, Spain, United States

Administrative Information

• NCT Number: NCT04898634
• 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 )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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
• URL: https://www.janssen.com/clinical-trials/transparency

• Current Responsible Party: Janssen Research & Development, LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Janssen Research & Development, LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Janssen Research & Development, LLC
• Verification Date: April 2024