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A Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of JNJ-63723283, an Anti-PD-1 Monoclonal Antibody, in Participants With Advanced Cancers

NCT02908906

Description:

The Primary purpose of this study is to identify the recommended Phase 2 dose [RP2D(s)] for JNJ-63723283 in Part 1 and to assess the anti-tumor activity of JNJ-63723283 at the RP2D(s) in participants with selected advanced cancers including non-small-cell lung cancer (NSCLC), melanoma, renal, bladder, small-cell lung cancer (SCLC), gastric/esophageal cancer, and high-level microsatellite instability (MSI-H) or mismatch repair-deficient (dMMR) colorectal cancer (CRC) in Part 2.

Related Conditions:
  • Bladder Carcinoma
  • Colorectal Carcinoma
  • Esophageal Carcinoma
  • Gastric Carcinoma
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Renal Cell Carcinoma
  • Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of JNJ-63723283, an Anti-PD-1 Monoclonal Antibody, in Participants With Advanced Cancers
  • Official Title: A First-in-Human, Open-label, Phase 1/2 Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of JNJ-63723283, an Anti-PD-1 Monoclonal Antibody, in Subjects With Advanced Cancers

Clinical Trial IDs

  • ORG STUDY ID: CR108223
  • SECONDARY ID: 2016-002017-22
  • SECONDARY ID: 63723283LUC1001
  • NCT ID: NCT02908906

Conditions

  • Neoplasms

Interventions

DrugSynonymsArms
JNJ-63723283JNJ-63723283

Purpose

The Primary purpose of this study is to identify the recommended Phase 2 dose [RP2D(s)] for JNJ-63723283 in Part 1 and to assess the anti-tumor activity of JNJ-63723283 at the RP2D(s) in participants with selected advanced cancers including non-small-cell lung cancer (NSCLC), melanoma, renal, bladder, small-cell lung cancer (SCLC), gastric/esophageal cancer, and high-level microsatellite instability (MSI-H) or mismatch repair-deficient (dMMR) colorectal cancer (CRC) in Part 2.

Detailed Description

      This is a First in Human (FIH), open-label (all people involved know the identity of the
      intervention), multicenter (more than 1 study site) study in participants with advanced
      cancers to establish the recommended Phase 2 dose (RP2D[s]) for JNJ-63723283 in Part 1 and to
      evaluate the safety and efficacy of the RP2D(s) in Part 2. Subject participation will include
      a Screening Phase (28 Days) during which participant eligibility will be reviewed prior to
      administration of the first dose of JNJ-63723283; a Treatment Phase that will start at the
      first dose and continue until treatment is discontinued; and a Survival Follow-up Phase
      starting upon completion of the End-of-Treatment Visit and ends when the participant
      completes or withdraws from the study. The end of the study is defined as last study
      assessment for the last participant on study or if the sponsor terminates the study,
      whichever comes first. Participants safety will be monitored throughout the study.
    

Trial Arms

NameTypeDescriptionInterventions
JNJ-63723283ExperimentalIn Part 1, the first cohort will receive JNJ-63723283 at a starting dose of 80 milligram (mg), intravenously (IV) every 2 weeks. JNJ-63723283 doses will be escalated following a modified Continual Reassessment Method (mCRM). Multiple doses and schedules may be explored. In Part 2, participants will receive JNJ-63723283 at the recommended Phase 2 dose (RP2D) determined in Part 1.
  • JNJ-63723283

Eligibility Criteria

        Inclusion Criteria:

          -  Have an Eastern Cooperative Oncology Group [ECOG] performance status 0 or 1

          -  Has thyroid function laboratory values within normal range

          -  Women of childbearing potential must have a negative serum pregnancy test

          -  Willing and able to adhere to the prohibitions and restrictions specified in this
             protocol

          -  Participants enrolled into Part 2 must have tumor tissue available for correlative
             studies. Fresh tumor biopsy is preferred. Archival tissue must meet the following
             criteria: archival sections within 4 months of sectioning that have been stored at 2
             degree to 8 degree Celsius in the dark or archival tumor blocks within 5 years of
             collection. Participants without tissues meeting the aforementioned archived tissue
             criteria must undergo a fresh biopsy

        Exclusion Criteria:

          -  Has uncontrolled intercurrent illness, including but not limited to ongoing or active
             infection requiring IV antibiotics, symptomatic congestive heart failure (New York
             Heart Association class III-IV), unstable angina pectoris, cardiac arrhythmia, poorly
             controlled hypertension or diabetes, or psychiatric illness/social situation that
             would limited compliance with study requirements

          -  Has had prior treatment with an anti-Programmed-cell death receptor-1 (PD-1) antibody,
             anti-the ligand to programmed-cell death 1 (PD-L1) antibody or anti-the ligand to
             programmed-cell death 2 (PD-L2) antibody

          -  Treatment with any local or systemic anti-neoplastic therapy, radiotherapy (excluding
             limited palliative radiation), or investigational anticancer agent within 14 days or 4
             halflives, whichever is longer, up to a maximum wash-out period of 28 days prior to
             the initiation of study drug administration

          -  Grade 3 or higher toxicity effects from previous treatment with immunotherapy

          -  A woman who is pregnant, breast-feeding, or planning to become pregnant while enrolled
             in this study or within 5 months after the last dose of study drug
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Frequency and Severity of Dose-Limiting Toxicity (DLT)
Time Frame:Approximate 2.5 years
Safety Issue:
Description:Objective Response Rate (ORR) is defined as percentage of subjects with best objective response of complete response (CR) or partial response (PR) based on Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) criteria.

Secondary Outcome Measures

Measure:Number of Participants With Adverse Events as a Measure of Safety
Time Frame:Approximate 2.5 years
Safety Issue:
Description:
Measure:Maximum Observed Serum Concentration (Cmax)
Time Frame:Approximate 2.5 years
Safety Issue:
Description:The Cmax is the maximum observed serum concentration.
Measure:Area Under the Concentration-Time Curve Between t1 and t2 (AUCt1-t2)
Time Frame:Approximate 2.5 years
Safety Issue:
Description:
Measure:Elimination Half-Life (t1/2)
Time Frame:Approximate 2.5 years
Safety Issue:
Description:The elimination half-life (t1/2) is the time measured for the serum concentration to decrease by 1 half to its original concentration.
Measure:Total Systemic Clearance of (CL)
Time Frame:Approximate 2.5 years
Safety Issue:
Description:Systemic Clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the body.
Measure:Volume of Distribution at Steady-State (Vss)
Time Frame:Approximate 2.5 years
Safety Issue:
Description:The Vss is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of JNJ-63723283 at steady state.
Measure:Accumulation Ratio (R)
Time Frame:Approximate 2.5 years
Safety Issue:
Description:The R is obtained by dividing AUC at two different time points.
Measure:Presence of Anti-JNJ-63723283 Antibodies and Effect on Serum JNJ-63723283 Concentrations
Time Frame:Approximate 2.5 years
Safety Issue:
Description:Serum samples will be screened for antibodies binding to JNJ-63723283. The titer of confirmed positive samples will be reported.
Measure:Overall Response Rate (ORR) per Immune-Related Response Criteria (irRC)
Time Frame:Approximate 2.5 years
Safety Issue:
Description:ORR is defined as percentage of subjects with best objective response of complete response (CR) or partial response (PR) based on irRC criteria.
Measure:Duration of Response (DOR) per RECIST v1.1
Time Frame:Approximate 2.5 years
Safety Issue:
Description:For Participants who achieve CR or PR, DOR will be calculated as time from initial response of CR or partial response (PR) to progressive disease or death due to underlying disease whichever comes first.
Measure:Duration of Response (DOR) per irRC
Time Frame:Approximate 2.5 years
Safety Issue:
Description:For Participants who achieve CR or PR (defined by irRC), DOR will be calculated as time from initial response of CR or partial response (PR) to progressive disease or death due to underlying disease whichever comes first.
Measure:Progression-free Survival (PFS) per RECIST v1.1
Time Frame:Approximate 2.5 years
Safety Issue:
Description:The time from first dose of JNJ-63723283 to progressive disease as defined by RECIST v 1.1 or death due to any cause.
Measure:Progression-free Survival (PFS) per irRC
Time Frame:Approximate 2.5 years
Safety Issue:
Description:The time from first dose of JNJ-63723283 to progressive disease as defined by irRC or death due to any cause.
Measure:Overall Survival (OS)
Time Frame:Approximate 2.5 years
Safety Issue:
Description:The time from first dose of JNJ-63723283 to death due to any cause.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Janssen Research & Development, LLC

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