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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02829099
Recruitment Status : Completed
First Posted : July 12, 2016
Last Update Posted : October 26, 2021
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Tracking Information
First Submitted Date  ICMJE July 7, 2016
First Posted Date  ICMJE July 12, 2016
Last Update Posted Date October 26, 2021
Actual Study Start Date  ICMJE September 21, 2016
Actual Primary Completion Date July 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 19, 2017)
  • Incidence of dose-limiting toxicities (Part 1) [ Time Frame: Up to 28 days ]
    Dose-limiting toxicities will be reviewed as a subset of adverse events that occur within the first 28 days of dosing and meet protocol-specified criteria.
  • Incidence of adverse events (Part 1 and 2) [ Time Frame: From signing of informed consent form (ICF) until 30 days after last dose of study drug (approximately up to 29 Months) ]
Original Primary Outcome Measures  ICMJE
 (submitted: July 7, 2016)
  • Incidence of dose-limiting toxicities (Part 1) [ Time Frame: Up to 28 days ]
    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.
  • Incidence of adverse events (Part 1 and 2) [ Time Frame: From signing of informed consent form (ICF) until 30 days after last dose of study drug (approximately up to 29 Months) ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 19, 2017)
  • Overall response rate (ORR) [ Time Frame: Disease assessment will continue until progression or lost to follow-up (approximately up to 29 months) ]
    The ORR is the proportion of participants with confirmed best objective response of complete response (CR) or immune-related CR (irCR).
  • Duration of Response (DOR) [ Time Frame: Disease assessment will continue until progression or lost to follow-up (approximately up to 29 months) ]
    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.
  • Progression-free Survival (PFS) [ Time Frame: Disease assessment will continue until progression or lost to follow-up (approximately up to 29 months) ]
    PFS is defined as the time from first dose of JNJ-64457107 to progressive disease or death due to any cause, whichever occurs first.
  • Overall Survival (OS) [ Time Frame: Disease assessment will continue until progression or lost to follow-up (approximately up to 29 months) ]
    Overall survival is defined as the time from first dose of JNJ-64457107 to date of death from any cause.
  • Maximum observed serum concentration (Cmax) of JNJ-64457107 [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 15: predose, 1, 4, 24, 48, 72 hours post end of infusion (EOI); any time (Cycle 1 Day 8 and Cycle 2 Day 22); predose (Cycle 1 Day 15 and Cycle 3 and 4); end of treatment ]
  • Time of maximum observed serum concentration (Tmax) of JNJ-64457107 [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 15: predose, 1, 4, 24, 48, 72 hours post end of infusion (EOI); any time (Cycle 1 Day 8 and Cycle 2 Day 22); predose (Cycle 1 Day 15 and Cycle 3 and 4); end of treatment ]
    The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
  • Area under the serum concentration versus time curve from time 0 to infinity (AUCinf) of JNJ-64457107 [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 15: predose, 1, 4, 24, 48, 72 hours post end of infusion (EOI); any time (Cycle 1 Day 8 and Cycle 2 Day 22); predose (Cycle 1 Day 15 and Cycle 3 and 4); end of treatment ]
    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.
  • 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 Day 1 and Cycle 2 Day 15: predose, 1, 4, 24, 48, 72 hours post end of infusion (EOI); any time (Cycle 1 Day 8 and Cycle 2 Day 22); predose (Cycle 1 Day 15 and Cycle 3 and 4); end of treatment ]
  • Area under the serum concentration versus time curve during a dosing interval (AUCtau) of JNJ-64457107 [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 15: predose, 1, 4, 24, 48, 72 hours post end of infusion (EOI); any time (Cycle 1 Day 8 and Cycle 2 Day 22); predose (Cycle 1 Day 15 and Cycle 3 and 4); end of treatment ]
  • Immunogenicity of JNJ-64457107 when administered IV [ Time Frame: Cycle 1: predose on Day 1; Cycle 2: predose on Day 1; Cycles 3, 4: predose; end of treatment visit ]
    Detection and characterization of antibodies to JNJ-64457107
Original Secondary Outcome Measures  ICMJE
 (submitted: July 7, 2016)
  • Overall response rate (ORR) [ Time Frame: Disease assessment will continue until progression or lost to follow-up (approximately up to 29 months) ]
    The ORR is the proportion of participants with confirmed best objective response of complete response (CR) or immune-related CR (irCR).
  • Duration of Response (DOR) [ Time Frame: Disease assessment will continue until progression or lost to follow-up (approximately up to 29 months) ]
    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.
  • Progression-free Survival (PFS) [ Time Frame: Disease assessment will continue until progression or lost to follow-up (approximately up to 29 months) ]
    PFS is defined as the time from first dose of JNJ-64457107 to progressive disease or death due to any cause, whichever occurs first.
  • Overall Survival (OS) [ Time Frame: Disease assessment will continue until progression or lost to follow-up (approximately up to 29 months) ]
    Overall survival is defined as the time from first dose of JNJ-64457107 to date of death from any cause.
  • 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 ]
  • 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 ]
    The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
  • 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 ]
    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.
  • 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 ]
  • 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 ]
  • 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 ]
    Detection and characterization of antibodies to JNJ-64457107
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Safety, Pharmacokinetics and Pharmacodynamics of JNJ-64457107 in Participants With Advanced Stage Tumors
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description This study has 2 parts: Dose Escalation (part 1) and Dose Expansion (part 2) which are conducted in 3 phases: Screening Phase (up to 28 days prior to first dose of study drug and includes procedures like electrocardiogram [ECG], serum pregnancy test), Treatment phase (continues until the completion of the End-of-Treatment Visit [30 days after last dose of study drug]) and Post-treatment follow-up phase (continues until the participant has died, is lost to follow-up, or has withdrawn consent or the study ends). In follow-up, participants will continue to be monitored for survival status and subsequent cancer-related therapies until the end of study. Additional bio-markers will be assessed, in an optional sub-study, to define the impact of JNJ-64457107 on innate and adaptive immune responses in tumors. Safety will be monitored throughout the study by Safety Evaluation Team (SET).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Neoplasms
Intervention  ICMJE Drug: JNJ-64457107
JNJ-64457107 administered by IV infusion on Day 1 and 14 of a 28-day cycle.
Other Name: ADC1013
Study Arms  ICMJE Experimental: JNJ-64457107
In 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.
Intervention: Drug: JNJ-64457107
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 5, 2019)
95
Original Estimated Enrollment  ICMJE
 (submitted: July 7, 2016)
114
Actual Study Completion Date  ICMJE July 29, 2021
Actual Primary Completion Date July 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Israel,   Spain
Removed Location Countries Australia,   Belgium,   Denmark,   Sweden,   United States
 
Administrative Information
NCT Number  ICMJE NCT02829099
Other Study ID Numbers  ICMJE CR108186
64457107CAN1001 ( Other Identifier: Janssen Research & Development, LLC )
2016-000969-23 ( EudraCT 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  ICMJE Not Provided
Current Responsible Party Janssen Research & Development, LLC
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Janssen Research & Development, LLC
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
PRS Account Janssen Research & Development, LLC
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP