A Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of JNJ-63723283, an Anti-Programmed Cell Death (PD)-1 Monoclonal Antibody, as Monotherapy or in Combination With Erdafitinib in Japanese Participants With Advanced Solid Cancers

Sponsor
Janssen Pharmaceutical K.K. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03547037
Collaborator
(none)
21
2
2
51.2
10.5
0.2

Study Details

Study Description

Brief Summary

The primary purpose of this study is to identify the recommended Phase 2 dose (RP2D) of JNJ-63723283 as a monotherapy (Phase 1a part) and to identify the RP2D of JNJ-63723283 when administered in combination with Erdafitinib (Phase 1b part).

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
21 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/1b Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of JNJ-63723283, an Anti-PD-1 Monoclonal Antibody, as Monotherapy or in Combination With Erdafitinib in Japanese Subjects With Advanced Solid Cancers
Actual Study Start Date :
Aug 31, 2018
Anticipated Primary Completion Date :
Aug 31, 2022
Anticipated Study Completion Date :
Dec 5, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Phase 1a: JNJ-63723283 (Monotherapy)

Participants will receive monotherapy of JNJ-63723283 intravenously. The subsequent dose levels of JNJ-63723283 will be escalated using Bayesian logistic regression model (BLRM).

Drug: JNJ-63723283
JNJ-63723283 will be administered intravenously.
Other Names:
  • Cetrelimab
  • Experimental: Phase 1b: Erdafitinib Combination

    Participants will receive erdafitinib in combination with JNJ-63723283 which will be escalated using BLRM.

    Drug: JNJ-63723283
    JNJ-63723283 will be administered intravenously.
    Other Names:
  • Cetrelimab
  • Drug: Erdafitinib
    Erdafitinib will be administered orally.

    Outcome Measures

    Primary Outcome Measures

    1. Phase 1a and Phase 1b: Number of Participants with Dose Limiting Toxicity (DLT) [Up to 6 weeks (maximum)]

      The DLTs are based on drug-related adverse events and defined as any of the following events: Infusion-related reactions, non-hematologic toxicity of Grade 3 or higher, or certain hematologic toxicity.

    2. Phase 1a and Phase 1b: Severity of DLT as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) [Up to 6 weeks (maximum)]

      Severity of DLT will be graded by using NCI-CTCAE, version 4.03. Severity scale ranges from Grade 1 to Grade 5 with Grades as follows: Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe), Grade 4 (Life-threatening), and Grade 5 (Death).

    Secondary Outcome Measures

    1. Phase 1b: Number of Participants with Adverse Events and Immune-Related Adverse Event (irAE) by Severity [Approximately up to 3 years]

      An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Severity of Adverse Event will be graded by using NCI-CTCAE, version 4.03. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death) with Grades as follows: Grade 1 (Mild) Grade 2 (Moderate), Grade 3 (Severe), Grade 4 (Life threatening) and Grade 5 (Death).

    2. Phase 1a and Phase 1b: Number of Participants With Clinically Significant Changes in Vital Signs as a Measure of Safety and Tolerability [Approximately up to 3 years]

      Number of participants with clinically significant changes in the vital signs including blood pressure, pulse rate, and body temperature will be reported.

    3. Phase 1a and Phase 1b: Number of Participants With Clinical Laboratory Abnormalities as a Measure of Safety and Tolerability [Approximately up to 3 years]

      Number of participants with clinical laboratory abnormalities (clinical laboratory tests include the following: hematology panel, coagulation panel, serum chemistry panel, endocrine panel, serology and pregnancy test [women only]) will be reported.

    4. Phase 1a and Phase 1b: Number of Participants With ECG Abnormalities as a Measure of Safety and Tolerability [Approximately up to 3 years]

      Number of participants with electrocardiogram (ECG) abnormalities will be reported.

    5. Phase 1a and Phase 1b: Maximum Serum Concentration (Cmax) of JNJ-63723283 [Approximately up to 3 years]

      The Cmax is the maximum observed serum concentration.

    6. Phase 1a and Phase 1b: Serum Concentration Immediately Prior to the Next Drug Administration (Ctrough) of JNJ-63723283 [Approximately up to 3 years]

      Ctrough is the serum concentration immediately prior to the next drug administration of any dose other than the first dose in a multiple dosing regimen.

    7. Phase 1a and Phase 1b: Time to reach Maximum Observed serum Concentration (Tmax) of JNJ-63723283 [Approximately up to 3 years]

      The Tmax is defined as actual sampling time to reach maximum observed serum concentration.

    8. Phase 1a and Phase 1b: Area Under the Serum Concentration-Time Curve Between 2 Defined Sampling Points, (t1 and t2) (AUC[t1-t2]) of JNJ-63723283 [Approximately up to 3 years]

      The AUC(t1-t2) is the area under the serum concentration-time curve between 2 defined sampling points, t1 and t2.

    9. Phase 1a and Phase 1b: Elimination Half-Life (t1/2) of JNJ-63723283 [Approximately up to 3 years]

      T1/2 is the time measured for the serum concentration to decrease by 1 half to its original concentration.

    10. Phase 1a and Phase 1b: Total Systemic Clearance (CL) of JNJ-63723283 [Approximately up to 3 years]

      CL is a quantitative measure of the rate at which JNJ-63723283 is removed from the body.

    11. Phase 1a and Phase 1b: Volume of Distribution at Steady-State (Vss) of JNJ-63723283 [Approximately up to 3 years]

      Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution is the apparent volume of distribution at steady-state.

    12. Phase 1b: Cmax of Erdafitinib [Approximately up to 3 years]

      The Cmax is the maximum observed plasma concentration.

    13. Phase 1b: Ctrough of Erdafitinib [Approximately up to 3 years]

      Ctrough is the plasma concentration immediately prior to the next drug administration of any dose other than the first dose in a multiple dosing regimen.

    14. Phase 1a and Phase 1b: Number of Participants With Anti-JNJ 63723283 Antibodies [Approximately up to 3 years]

      Number of participants with anti-JNJ 63723283 antibodies will be assessed.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    20 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Radiographically, histologically, or cytologically confirmed advanced or refractory solid tumor(s) that is metastatic or unresectable, and previously received or was ineligible for standard treatment options. Participants with solid tumor(s) for which anti-PD-1 or anti-PD-L1 antibody as a monotherapy is approved in Japan are eligible.

    • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

    • Thyroid function laboratory values within normal range

    • A woman must be: a) Not of childbearing potential; b) Of childbearing potential and practicing a highly effective, preferably user-independent method of contraception (failure rate of less than (<) 1 percent (%) per year when used consistently and correctly) and agrees to remain on a highly effective method while receiving study intervention and continue for 5 months following discontinuation of JNJ-63723283 or 3 months following discontinuation of erdafitinib, whichever is longer. Especially participants receiving erdafitinib must agree to use two contraceptive methods and one must be user-independent method; Examples of highly effective contraceptives include: user-independent methods: intrauterine device (IUD) or intrauterine contraceptive system (IUS) and user-dependent methods: combined (estrogen- and progestogen-containing) hormonal contraception or progesterone-containing hormonal contraception. c) Agree not to donate eggs (ova, oocytes), during the study and continue for 5 months following discontinuation of JNJ-63723283 or 3 months following discontinuation of erdafitinib, whichever is longer

    • A male participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person and must agree not to donate sperm for 5 months following discontinuation of JNJ-63723283 or 5 months following discontinuation of erdafitinib, whichever is longer

    Exclusion Criteria:
    • Had prior treatment with an anti-PD-1 antibody, anti-PD-L1 antibody or anti-PDL2 antibody within 30 days of first study drug administration and/or has an ongoing Grade 2 or higher immunotherapy-related toxicity. If the subject has an experience of treatment with these agents, the subject must not have had severe immunotherapy-related toxicity

    • History of or concurrent interstitial lung disease

    • Active autoimmune disease or a documented history of autoimmune disease that requires systemic steroids or immunosuppressive agents

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

    • Has taken immunosuppressive doses of systemic medications, such as corticosteroids doses greater than (>) 10 milligram per day (mg/day) prednisolone or equivalent), within 2 weeks before the planned first dose of study drug

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 National Cancer Center Hospital Chuo-Ku Japan 104-0045
    2 National Cancer Center Hospital East Kashiwa Japan 277-8577

    Sponsors and Collaborators

    • Janssen Pharmaceutical K.K.

    Investigators

    • Study Director: Janssen Pharmaceutical K.K., Japan Clinical Trial, Janssen Pharmaceutical K.K.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Janssen Pharmaceutical K.K.
    ClinicalTrials.gov Identifier:
    NCT03547037
    Other Study ID Numbers:
    • CR108471
    • 63723283LUC1002
    First Posted:
    Jun 6, 2018
    Last Update Posted:
    Aug 12, 2022
    Last Verified:
    Aug 1, 2022
    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

    Study Results

    No Results Posted as of Aug 12, 2022