Clinical Trials /

A Study of Safety, Pharmacokinetics and Pharmacodynamics of JNJ-64457107 in Participants With Advanced Stage Tumors

NCT02829099

Description:

The primary purpose of the study is to determine the recommended Phase 2 dose (RP2D) and schedule of JNJ-64457107 when administered intravenously (IV) to participants with advanced stage solid tumors in Part 1 and to further characterize the safety of JNJ-64457107 when administered IV to participants with non-small cell lung cancer (NSCLC), pancreatic cancer and cutaneous melanoma in Part 2.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of Safety, Pharmacokinetics and Pharmacodynamics of JNJ-64457107 in Participants With Advanced Stage Tumors
  • Official Title: A Phase 1, Open-Label Study of the Safety, Pharmacokinetics and Pharmacodynamics of JNJ-64457107, an Agonistic Human Monoclonal Antibody Targeting CD40 in Patients With Advanced Stage Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: CR108186
  • SECONDARY ID: 64457107CAN1001
  • SECONDARY ID: 2016-000969-23
  • NCT ID: NCT02829099

Conditions

  • Advanced Solid Neoplasms

Interventions

DrugSynonymsArms
JNJ-64457107ADC1013JNJ-64457107

Purpose

The primary purpose of the study is to determine the recommended Phase 2 dose (RP2D) and schedule of JNJ-64457107 when administered intravenously (IV) to participants with advanced stage solid tumors in Part 1 and to further characterize the safety of JNJ-64457107 when administered IV to participants with non-small cell lung cancer (NSCLC), pancreatic cancer and cutaneous melanoma in Part 2.

Trial Arms

NameTypeDescriptionInterventions
JNJ-64457107ExperimentalIn Part 1, the first cohort will receive JNJ-64457107 at a starting dose of 75 microgram per kilogram (mcg/kg). The proposed treatment schedule is intravenous (IV) dosing every 14 days. JNJ-64457107 doses will be escalated following a modified Continual Reassessment Method (mCRM); the JNJ-64457107 dose will be increased by not more than half-logarithmical (3.2-fold) dose increments. Dose escalation will continue until the maximum tolerated dose (MTD) and/or RP2D of JNJ-64457107 are defined or the maximum-administered dose (MAD) has been reached. In Part 2, subjects will receive JNJ-64457107 at the RP2D and regimen determined in Part 1.
  • JNJ-64457107

Eligibility Criteria

        Inclusion Criteria:

          -  Part 1: advanced stage solid tumors; Part 2: non-small cell lung cancer (NSCLC),
             pancreatic cancer and cutaneous melanoma

          -  Eastern cooperative oncology group (ECOG) performance score of 0 or 1

          -  Adequate organ function as defined in the protocol

          -  A woman of childbearing potential must have a negative highly sensitive serum
             (beta-human chorionic gonadotropin [beta-hCG]) pregnancy test at Screening and a
             negative urine pregnancy test prior to the first dose of study drug

          -  During the study and for at least 120 days after receiving the last dose of study
             drug, in addition to the highly effective method of contraception, a man who is
             sexually active with a woman of childbearing potential must agree to use a barrier
             method of contraception (example [eg.], condom with spermicidal
             foam/gel/film/cream/suppository), or who is sexually active with a woman who is
             pregnant must use a condom

        Exclusion Criteria:

          -  Malignancy other than the disease under study within 2 years before screening
             (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ
             of the cervix, or malignancy that in the opinion of the investigator, with
             concurrence with the sponsor's medical monitor, is considered cured with minimal risk
             of recurrence)

          -  Symptomatic brain metastases; asymptomatic brain metastases are allowed provided that
             they have been treated, have been stable for greater than (>) 6 weeks as documented
             by radiographic imaging, and do not require prolonged (>14 days) systemic
             corticosteroid therapy

          -  Treatment with any local or systemic anti-neoplastic therapy or investigational
             anticancer agent within 14 days or 4 half-lives, whichever is longer, up to a maximum
             wash-out period of 28 days prior to the initiation of study drug administration

          -  Toxicities from previous anti-cancer therapies have not resolved to baseline levels
             or to Grade 1 or less except for alopecia and peripheral neuropathy

          -  Major surgery (eg., requiring general anesthesia) within 3 weeks before screening, or
             will not have fully recovered from surgery, or has surgery planned during the time
             the subject is expected to participate in the study
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of dose-limiting toxicities (Part 1)
Time Frame:Up to 28 days
Safety Issue:
Description:Dose-limiting toxicities will reviewed as a subset of adverse events that occur within the first 28 days of dosing and meet protocol-specified criteria.

Secondary Outcome Measures

Measure:Overall response rate (ORR)
Time Frame:Disease assessment will continue until progression or lost to follow-up (approximately up to 29 months)
Safety Issue:
Description:The ORR is the proportion of participants with confirmed best objective response of complete response (CR) or immune-related CR (irCR).
Measure:Duration of Response (DOR)
Time Frame:Disease assessment will continue until progression or lost to follow-up (approximately up to 29 months)
Safety Issue:
Description:For participants who achieve CR or partial response (PR), DOR will be calculated as time from initial response of CR or PR to progressive disease or death due to underlying disease, whichever comes first.
Measure:Progression-free Survival (PFS)
Time Frame:Disease assessment will continue until progression or lost to follow-up (approximately up to 29 months)
Safety Issue:
Description:PFS is defined as the time from first dose of JNJ-64457107 to progressive disease or death due to any cause, whichever occurs first.
Measure:Overall Survival (OS)
Time Frame:Disease assessment will continue until progression or lost to follow-up (approximately up to 29 months)
Safety Issue:
Description:Overall survival is defined as the time from first dose of JNJ-64457107 to date of death from any cause.
Measure:Maximum observed serum concentration (Cmax) of JNJ-64457107
Time Frame:Cycle 1: 1 hour before end of infusion (EOI), 1, 4, 24 hours post EOI (Day 1), any time (Day 8), predose (Day 15);Cycle 2: predose (Day 1), 1 hour before EOI, 1, 4, 24 hours post EOI (Day 15), anytime (Day 22);Cycles 3, 4: predose; end of treatment visit
Safety Issue:
Description:
Measure:Time of maximum observed serum concentration (Tmax) of JNJ-64457107
Time Frame:Cycle 1: 1 hour before end of infusion (EOI), 1, 4, 24 hours post EOI (Day 1), any time (Day 8), predose (Day 15);Cycle 2: predose (Day 1), 1 hour before EOI, 1, 4, 24 hours post EOI (Day 15), anytime (Day 22);Cycles 3, 4: predose; end of treatment visit
Safety Issue:
Description:The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
Measure:Area under the serum concentration versus time curve from time 0 to infinity (AUCinf) of JNJ-64457107
Time Frame:Cycle 1: 1 hour before end of infusion (EOI), 1, 4, 24 hours post EOI (Day 1), any time (Day 8), predose (Day 15);Cycle 2: predose (Day 1), 1 hour before EOI, 1, 4, 24 hours post EOI (Day 15), anytime (Day 22);Cycles 3, 4: predose; end of treatment visit
Safety Issue:
Description:The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.
Measure:Area under the serum concentration versus time curve from time 0 to the final quantifiable time point (t) [AUC(0-t)] of JNJ-64457107
Time Frame:Cycle 1: 1 hour before end of infusion (EOI), 1, 4, 24 hours post EOI (Day 1), any time (Day 8), predose (Day 15);Cycle 2: predose (Day 1), 1 hour before EOI, 1, 4, 24 hours post EOI (Day 15), anytime (Day 22);Cycles 3, 4: predose; end of treatment visit
Safety Issue:
Description:
Measure:Area under the serum concentration versus time curve during a dosing interval (AUCtau) of JNJ-64457107
Time Frame:Cycle 1: 1 hour before end of infusion (EOI), 1, 4, 24 hours post EOI (Day 1), any time (Day 8), predose (Day 15);Cycle 2: predose (Day 1), 1 hour before EOI, 1, 4, 24 hours post EOI (Day 15), anytime (Day 22);Cycles 3, 4: predose; end of treatment visit
Safety Issue:
Description:
Measure:Immunogenicity of JNJ-64457107 when administered IV
Time Frame:Cycle 1: 1 hour before end of infusion (EOI) on Day 1; Cycle 2: predose on Day 1; Cycles 3, 4: predose; end of treatment visit
Safety Issue:
Description:Detection and characterization of antibodies to JNJ-64457107

Details

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

Last Updated

March 31, 2017