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

Prostatic Neoplasms Clinical Trial

Official title:

A Phase 1 Study of JNJ-78278343, a T-Cell-Redirecting Agent Targeting Human Kallikrein 2 (KLK2), for Advanced Prostate Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04898634
• Other study ID #: CR108958
• Secondary ID: 2020-005970-8378
• Status: Recruiting
• Phase: Phase 1
• Start date: July 13, 2021
• Est. completion date: November 15, 2025

Study information

• Verified date: June 2024
• Source: Janssen Research & Development, LLC
• Contact: Study Contact
• Phone: 844-434-4210
• Email: Participate-In-This-Study[@]its.jnj.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 260
• Est. completion date: November 15, 2025
• Est. primary completion date: November 30, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Prostatic Neoplasms

Intervention

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

Locations

Country	Name	City	State
France	Centre Leon Berard	Lyon Cedex 8
France	APHM Hopital Timone	Marseille
France	Institut Gustave Roussy	Villejuif
Netherlands	NKI AVL Amsterdam	Amsterdam
Netherlands	Erasmus MC	Rotterdam
Spain	Hosp Univ Fund Jimenez Diaz	Madrid
Spain	Hosp. Univ. Hm Sanchinarro	Madrid
Spain	Hosp. Virgen de La Victoria	Málaga
United States	Columbia University Medical Center Herbert Irving Pavilion	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Washington	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  France,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	Serum Concentration of JNJ-78278343	Serum concentrations of JNJ-78278343 will be determined.	Up to 1 year and 10 months
Secondary	Systemic Cytokine Concentrations	Cytokine concentrations will be determined for biomarker assessment.	Up to 1 year and 10 months
Secondary	Serum Prostate Specific Antigen (PSA) Concentration	Serum PSA concentration will be measured.	Up to 1 year and 10 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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