Clinical trial NCT02829099: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Neoplasms
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2016-07-12
Enrollment: 95
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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drug\]) and Post-treatment follow-up phase (continues until the participant has died, is lost to follow-up, or has withdrawn consent or the study ends).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).

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

Primary outcomes:
measure: Incidence of dose-limiting toxicities (Part 1)
timeFrame: Up to 28 days
measure: Incidence of adverse events (Part 1 and 2)
timeFrame: From signing of informed consent form (ICF) until 30 days after last dose of study drug (approximately up to 29 Months)
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: Disease assessment will continue until progression or lost to follow-up (approximately up to 29 months)
measure: Duration of Response (DOR)
timeFrame: Disease assessment will continue until progression or lost to follow-up (approximately up to 29 months)
measure: Progression-free Survival (PFS)
timeFrame: Disease assessment will continue until progression or lost to follow-up (approximately up to 29 months)
measure: Overall Survival (OS)
timeFrame: Disease assessment will continue until progression or lost to follow-up (approximately up to 29 months)
measure: Maximum observed serum concentration (Cmax) of JNJ-64457107
timeFrame: 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
measure: Time of maximum observed serum concentration (Tmax) of JNJ-64457107
timeFrame: 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
measure: Area under the serum concentration versus time curve from time 0 to infinity (AUCinf) of JNJ-64457107
timeFrame: 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
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
timeFrame: 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
measure: Area under the serum concentration versus time curve during a dosing interval (AUCtau) of JNJ-64457107
timeFrame: 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
measure: Immunogenicity of JNJ-64457107 when administered IV
timeFrame: Cycle 1: predose on Day 1; Cycle 2: predose on Day 1; Cycles 3, 4: predose; end of treatment visit
Other outcomes:
Locations:
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Tel Aviv
country: Israel
city: Madrid
country: Spain
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: