Description:
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).
Title
- Brief Title: 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
- 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
Clinical Trial IDs
- ORG STUDY ID:
CR108223
- SECONDARY ID:
2016-002017-22
- SECONDARY ID:
63723283LUC1001
- NCT ID:
NCT02908906
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| JNJ-63723283 | Cetrelimab | JNJ-63723283 |
Purpose
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).
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| JNJ-63723283 | Experimental | 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. | |
Eligibility Criteria
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Part 1: Frequency and Severity of Dose-Limiting Toxicity (DLT) |
| Time Frame: | Approximate 2.5 years |
| Safety Issue: | |
| Description: | Frequency and severity of dose-limiting toxicity will be reported. |
Secondary Outcome Measures
| Measure: | Number of Participants With Adverse Events (AEs) as a Measure of Safety |
| Time Frame: | Approximate 2.5 years |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Maximum Observed Serum Concentration (Cmax) |
| Time Frame: | Approximate 2.5 years |
| Safety Issue: | |
| Description: | The Cmax is the maximum observed serum concentration. |
| Measure: | Parts 1 and 2: Area Under the Serum Concentration Versus Time Curve Between time t1 and t2 (AUC [t1-t2]) |
| Time Frame: | Approximate 2.5 years |
| Safety Issue: | |
| Description: | AUC (t1-t2) is defined as the area under the serum concentration versus time curve between time t1 and t2. |
| Measure: | Parts 1, 2 and 3: Elimination Half-Life (t1/2) |
| Time Frame: | Approximate 2.5 years |
| Safety Issue: | |
| Description: | The elimination half-life (t1/2) is the time measured for the serum concentration to decrease by 1 half to its original concentration. |
| Measure: | Parts 1 and 2: Total Systemic Clearance of (CL) |
| Time Frame: | Approximate 2.5 years |
| Safety Issue: | |
| Description: | Total systemic Clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the body. |
| Measure: | Parts 1 and 2: Volume of Distribution at Steady-State (Vss) |
| Time Frame: | Approximate 2.5 years |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Parts 1, 2 and 4: Accumulation Ratio (R) |
| Time Frame: | Approximate 2.5 years |
| Safety Issue: | |
| Description: | The R is obtained by dividing AUC at two different time points. |
| Measure: | Parts 3 and 4: Area Under the Serum Concentration Versus Time Curve Between Time Zero and Time t (AUC [0-t]) |
| Time Frame: | Up to 2 years and 5 months |
| Safety Issue: | |
| Description: | AUC (0-t) is defined as area under the serum concentration versus time curve between time zero and time t. |
| Measure: | Parts 3: Area Under the Serum Concentration Versus Time Curve from Time Zero to Infinity (AUC [0-Infinity]) |
| Time Frame: | Up to 2 years and 5 months |
| Safety Issue: | |
| Description: | AUC (0-infinity) is defined as area under the serum concentration versus time curve from time zero to infinity. |
| Measure: | Parts 3 and 4: Concentration just Prior to the Beginning of at the end of a Dosing Interval (Ctrough) |
| Time Frame: | Up to 2 years and 5 months |
| Safety Issue: | |
| Description: | Ctrough is defined as the concentration just prior to the beginning of at the end of a dosing interval. |
| Measure: | Presence of Anti-JNJ-63723283 Antibodies and Effect on Serum JNJ-63723283 Concentrations |
| Time Frame: | Approximate 2.5 years |
| Safety Issue: | |
| Description: | Serum samples will be analyzed for antibodies to JNJ-63723283. The titer of the confirmed positive samples will be reported. |
| Measure: | Overall Response Rate (ORR) per Immune-Related Response Criteria (irRC) |
| Time Frame: | Approximate 2.5 years |
| Safety Issue: | |
| Description: | ORR is defined as percentage of subjects with best objective response of complete response (CR) or partial response (PR) based on irRC criteria. |
| Measure: | Duration of Response (DOR) per RECIST v1.1 |
| Time Frame: | Approximate 2.5 years |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Duration of Response (DOR) per irRC |
| Time Frame: | Approximate 2.5 years |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Clinical Benefit Rate (CBR) per RECIST v1.1 |
| Time Frame: | Approximate 2.5 years |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Clinical Benefit Rate per irRC |
| Time Frame: | Approximate 2.5 years |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Progression-free Survival (PFS) per RECIST v1.1 |
| Time Frame: | Approximate 2.5 years |
| Safety Issue: | |
| Description: | The time from first dose of JNJ-63723283 to progressive disease as defined by RECIST v 1.1 or death due to any cause. |
| Measure: | Progression-free Survival (PFS) per irRC |
| Time Frame: | Approximate 2.5 years |
| Safety Issue: | |
| Description: | The time from first dose of JNJ-63723283 to progressive disease as defined by irRC or death due to any cause. |
| Measure: | Overall Survival (OS) |
| Time Frame: | Approximate 2.5 years |
| Safety Issue: | |
| Description: | The time from first dose of JNJ-63723283 to death due to any cause. |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Janssen Research & Development, LLC |
Last Updated
August 13, 2021
