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

Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Recruiting
CT.gov ID
NCT02908906
Collaborator
(none)
250
33
1
75.8
7.6
0.1

Study Details

Study Description

Brief Summary

The Primary purpose of this study is to identify the recommended Phase 2 dose [RP2D(s)] for JNJ-63723283 in Part 1, 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 and to determine one or more additional RP2Ds (Part 3 and Part 4).

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 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]) with IV administration for JNJ-63723283 in Part 1, to evaluate the safety and efficacy of the IV RP2D(s) in Part 2 and to determine one or more additional RP2Ds in Parts 3 and 4. Participant 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 (applicable for Part 1 and 2) 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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
250 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Nov 21, 2016
Anticipated Primary Completion Date :
Feb 15, 2023
Anticipated Study Completion Date :
Mar 16, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: JNJ-63723283

In Part 1, the first cohort will receive JNJ-63723283 at a starting dose of 80 milligram (mg), IV every 2 weeks. JNJ-63723283 doses will be escalated following a modified Continual Reassessment Method (mCRM). Multiple doses, dose administration routes (subcutaneous [SC] or IV), and dose schedules may be explored. In Part 2, participants will receive JNJ-63723283 at the recommended Phase 2 dose (RP2D) determined in Part 1. In Part 3, participants will receive JNJ-63723283 to evaluate pharmacokinetic (PK), pharmacodynamic (PD) and safety. In Part 4, participants will receive JNJ-63723283 at the dose level determined in Part 3. Additional cohorts may be enrolled in Part 4 to evaluate additional doses.

Drug: JNJ-63723283
JNJ-63723283 will be administered by IV infusion or SC injection or infusion.
Other Names:
  • Cetrelimab
  • Outcome Measures

    Primary Outcome Measures

    1. Part 1: Frequency and Severity of Dose-Limiting Toxicity (DLT) [Approximate 2.5 years]

      Frequency and severity of dose-limiting toxicity will be reported.

    2. Part 2: Overall Response Rate (ORR) per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in Subjects With Selected Advanced Solid Tumors [Approximate 2.5 years]

      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.

    3. Parts 3 and 4: Area Under the Serum Concentration Versus Time Curve from Time Zero to Dosing Interval (AUC [0-tau]) [Up to 2 years and 5 months]

      AUC (0-tau) is defined as area under the serum concentration versus time curve from time zero to dosing interval.

    Secondary Outcome Measures

    1. Number of Participants With Adverse Events (AEs) as a Measure of Safety [Approximate 2.5 years]

      An AE is any untoward medical occurrence in a clinical study participant administered a investigational or non-investigational medicinal product. An AE does not necessarily have a causal relationship with the treatment.

    2. Maximum Observed Serum Concentration (Cmax) [Approximate 2.5 years]

      The Cmax is the maximum observed serum concentration.

    3. Parts 1 and 2: Area Under the Serum Concentration Versus Time Curve Between time t1 and t2 (AUC [t1-t2]) [Approximate 2.5 years]

      AUC (t1-t2) is defined as the area under the serum concentration versus time curve between time t1 and t2.

    4. Parts 1, 2 and 3: Elimination Half-Life (t1/2) [Approximate 2.5 years]

      The elimination half-life (t1/2) is the time measured for the serum concentration to decrease by 1 half to its original concentration.

    5. Parts 1 and 2: Total Systemic Clearance of (CL) [Approximate 2.5 years]

      Total systemic Clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the body.

    6. Parts 1 and 2: Volume of Distribution at Steady-State (Vss) [Approximate 2.5 years]

      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.

    7. Parts 1, 2 and 4: Accumulation Ratio (R) [Approximate 2.5 years]

      The R is obtained by dividing AUC at two different time points.

    8. Parts 3 and 4: Area Under the Serum Concentration Versus Time Curve Between Time Zero and Time t (AUC [0-t]) [Up to 2 years and 5 months]

      AUC (0-t) is defined as area under the serum concentration versus time curve between time zero and time t.

    9. Parts 3: Area Under the Serum Concentration Versus Time Curve from Time Zero to Infinity (AUC [0-Infinity]) [Up to 2 years and 5 months]

      AUC (0-infinity) is defined as area under the serum concentration versus time curve from time zero to infinity.

    10. Parts 3 and 4: Concentration just Prior to the Beginning of at the end of a Dosing Interval (Ctrough) [Up to 2 years and 5 months]

      Ctrough is defined as the concentration just prior to the beginning of at the end of a dosing interval.

    11. Presence of Anti-JNJ-63723283 Antibodies and Effect on Serum JNJ-63723283 Concentrations [Approximate 2.5 years]

      Serum samples will be analyzed for antibodies to JNJ-63723283. The titer of the confirmed positive samples will be reported.

    12. Overall Response Rate (ORR) per Immune-Related Response Criteria (irRC) [Approximate 2.5 years]

      ORR is defined as percentage of subjects with best objective response of complete response (CR) or partial response (PR) based on irRC criteria.

    13. Duration of Response (DOR) per RECIST v1.1 [Approximate 2.5 years]

      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.

    14. Duration of Response (DOR) per irRC [Approximate 2.5 years]

      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.

    15. Clinical Benefit Rate (CBR) per RECIST v1.1 [Approximate 2.5 years]

      The CBR is defined as the percentage of participants who achieve CR, PR or stable disease (SD; greater than or equal to [>=] 24 weeks from the 1st study drug) based on RECIST v1.1 criteria.

    16. Clinical Benefit Rate per irRC [Approximate 2.5 years]

      The CBR is defined as the percentage of participants who achieve CR, PR or SD (>= 24 weeks from the 1st study drug) based on irRC criteria.

    17. Progression-free Survival (PFS) per RECIST v1.1 [Approximate 2.5 years]

      The time from first dose of JNJ-63723283 to progressive disease as defined by RECIST v 1.1 or death due to any cause.

    18. Progression-free Survival (PFS) per irRC [Approximate 2.5 years]

      The time from first dose of JNJ-63723283 to progressive disease as defined by irRC or death due to any cause.

    19. Overall Survival (OS) [Approximate 2.5 years]

      The time from first dose of JNJ-63723283 to death due to any cause.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Washington University School of Medicine Saint Louis Missouri United States 63110
    2 UPMC Cancer Centers Pittsburgh Pennsylvania United States 15232
    3 Ospedali Riuniti Di Ancona Ancona Italy 60126
    4 Ospedale San Giuseppe Moscati di Avellino Avellino Italy 83100
    5 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori Meldola Italy 47014
    6 Istituto Europeo di Oncologia Servizio Radioterapia Milano Italy 20141
    7 San Gerardo Hospital Monza Italy 20052
    8 IRCCS-Fondazione Pascale Napoli Italy 80131
    9 Aou San Luigi Gonzaga Orbassano Italy 10043
    10 Istituto Clinico Humanitas Rozzano Italy 20089
    11 Azienda Ospedaliera Universitaria Senese Siena Italy 53100
    12 Arensia Exploratory Medicine Chisinau Moldova, Republic of MD-2025
    13 Uniwersytecki Szpital Kliniczny w Bialymstoku, II Klinika Chorob Pluc i Gruzlicy Bialystok Poland 15-540
    14 Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy Warszawa Poland 02-781
    15 FSBSI 'N. N. Blokhin Russian Cancer Research Center' Moscow Russian Federation 115478
    16 Pyatigorsky Oncology Dispensary Pyatigorsk Russian Federation 357502
    17 BioEk, LLC St. Petersburg Russian Federation 197342
    18 City Oncology Dispensary St. Petersburg Russian Federation 198255
    19 City Oncology Dispensary St. Petersburg Russian Federation 198255
    20 Hosp. Univ. Germans Trias I Pujol Badalona Spain 8916
    21 Hosp. Univ. Vall D Hebron Barcelona Spain 8035
    22 Hosp. Gral. Univ. Gregorio MaraƱon Madrid Spain 28009
    23 Hosp. Univ. Fund. Jimenez Diaz Madrid Spain 28040
    24 Hosp. Univ. 12 de Octubre Madrid Spain 28041
    25 Hosp. Univ. Hm Sanchinarro Madrid Spain 28050
    26 Hosp. Virgen de La Victoria Malaga Spain 29010
    27 Clinica Univ. de Navarra Pamplona Spain 31008
    28 Hosp. Virgen Del Rocio Sevilla Spain 41013
    29 Hosp. Clinico Univ. de Valencia Valencia Spain 46010
    30 Beatson West Of Scotland Cancer Centre Glasgow United Kingdom G12 0YN
    31 Sarah Cannon Research Institute London United Kingdom W1G 6AD
    32 The Christie Nhs Foundation Trust Manchester United Kingdom M20 4BX
    33 Sir Bobby Robson Unit, Northern Centre for Cancer Care Newcastle upon Tyne United Kingdom NE7 7DN

    Sponsors and Collaborators

    • Janssen Research & Development, LLC

    Investigators

    • Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Janssen Research & Development, LLC
    ClinicalTrials.gov Identifier:
    NCT02908906
    Other Study ID Numbers:
    • CR108223
    • 2016-002017-22
    • 63723283LUC1001
    First Posted:
    Sep 21, 2016
    Last Update Posted:
    Aug 12, 2022
    Last Verified:
    Aug 1, 2022
    Studies a U.S. FDA-regulated Device Product:
    No

    Study Results

    No Results Posted as of Aug 12, 2022