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

Phase 1
Recruiting
Conditions
Prostatic Neoplasms
Interventions
Registration Number
NCT04898634
Lead Sponsor
Janssen Research & Development, LLC
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

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
Male
Target Recruitment
260
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 & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
JNJ-78278343JNJ-78278343Participants 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.
Primary Outcome Measures
NameTimeMethod
Part 1 and 2: Number of Participants With Adverse Events (AEs)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 SeverityUp 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)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.

Secondary Outcome Measures
NameTimeMethod
Serum Prostate Specific Antigen (PSA) ConcentrationUp to 1 year and 10 months

Serum PSA concentration will be measured.

Serum Concentration of JNJ-78278343Up to 1 year and 10 months

Serum concentrations of JNJ-78278343 will be determined.

Number of Participants With Anti-JNJ-78278343 AntibodiesUp to 1 year and 10 months

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

Radiographic Progression-free Survival (rPFS)Up to 1 year and 10 months

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.

PSA Response RateUp 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.

Systemic Cytokine ConcentrationsUp to 1 year and 10 months

Cytokine concentrations will be determined for biomarker assessment.

Objective Response Rate (ORR)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).

Duration of Response (DOR)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.

Trial Locations

Locations (17)

Sun Yat Sen University Cancer Center

🇨🇳

Guang Zhou Shi, China

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, United States

Peking University Third Hospital

🇨🇳

Beijing, China

Chongqing University Cancer Hospital

🇨🇳

Chongqing, China

First Affiliated Hospital Of Wenzhou Medical College

🇨🇳

Wen Zhou Shi, China

Centre Leon Berard

🇫🇷

Lyon Cedex 8, France

APHM Hopital Timone

🇫🇷

Marseille, France

Institut Gustave Roussy

🇫🇷

Villejuif, France

National Cancer Center Hospital East

🇯🇵

Kashiwa, Japan

Yokohama City University Medical Center

🇯🇵

Yokohama, Japan

Antoni van Leeuwenhoek

🇳🇱

Amsterdam, Netherlands

Erasmus MC

🇳🇱

Rotterdam, Netherlands

Hosp Univ Fund Jimenez Diaz

🇪🇸

Madrid, Spain

Hosp Univ Hm Sanchinarro

🇪🇸

Madrid, Spain

Hosp Virgen de La Victoria

🇪🇸

Málaga, Spain

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