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

Study Overview
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Brief Summary
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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, to determine one or more additional RP2Ds in Parts 3 and 4.

Official Title
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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

Conditions
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Neoplasms

Intervention / Treatment
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* Drug: JNJ-63723283


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Parts 1-4: Have an Eastern Cooperative Oncology Group [ECOG] performance status 0 or 1 Parts 1-4: Has thyroid function laboratory values within normal range Parts 1-4: Females of childbearing potential must have a negative serum pregnancy test Parts 1-4: Willing and able to adhere to the prohibitions and restrictions specified in this protocol For Part 2 only: 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 Parts 1 to 4: Have evaluable disease 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 half lives, 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 female 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JNJ-63723283<br>In Part 1, the first cohort will receive JNJ-63723283 at a starting dose of 80 milligram (mg), intravenous (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. | Drug: JNJ-63723283<br>* JNJ-63723283 will be administered by IV infusion or SC injection or infusion.<br>* Other names: Cetrelimab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Frequency and Severity of Dose-Limiting Toxicity (DLT) | Frequency and severity of dose-limiting toxicity will be reported. | Up to 2 years 6 months | 
| Part 2: Overall Response Rate (ORR) per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in Subjects With Selected Advanced Solid Tumors | 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. | Up to 2 years 6 months | 
| Parts 3 and 4: Area Under the Serum Concentration Versus Time Curve from Time Zero to Dosing Interval (AUC [0-tau]) | AUC (0-tau) is defined as area under the serum concentration versus time curve from time zero to dosing interval. | Up to 2 years 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parts 1, 2, 3, and 4 : Number of Participants With Adverse Events (AEs) as a Measure of Safety | 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. | Up to 2 years 6 months | 
| Parts 1, 2 and 3, and 4: Maximum Observed Serum Concentration (Cmax) | The Cmax is the maximum observed serum concentration. | Up to 2 years 6 months | 
| Parts 1 and 2: Area Under the Serum Concentration Versus Time Curve Between time t1 and t2 (AUC [t1-t2]) | AUC (t1-t2) is defined as the area under the serum concentration versus time curve between time t1 and t2. | Up to 2 years 6 months | 
| Parts 1, 2 and 3: Elimination Half-Life (t1/2) | The elimination half-life (t1/2) is the time measured for the serum concentration to decrease by 1 half to its original concentration. | Up to 2 years 6 months | 
| Parts 1 and 2: Total Systemic Clearance of (CL) | Total systemic Clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the body. | Up to 2 years 6 months | 
| Parts 1 and 2: Volume of Distribution at Steady-State (Vss) | 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. | Up to 2 years 6 months | 
| Parts 1 and 2: Accumulation Ratio (R) | The R is obtained by dividing AUC at two different time points. | Up to 2 years 6 months | 
| Parts 3 and 4: Average Concentration (Cavg) of JNJ-63723283 | Cavg of JNJ-63723283 will be reported. | Up to 2 years 6 months | 
| Parts 3 and 4: Area Under the Serum Concentration Versus Time Curve Between Time Zero and Time t (AUC [0-t]) | AUC (0-t) is defined as area under the serum concentration versus time curve between time zero and time t. | Up to 2 years 6 months | 
| Parts 3: Area Under the Serum Concentration Versus Time Curve from Time Zero to Infinity (AUC [0-Infinity]) | AUC (0-infinity) is defined as area under the serum concentration versus time curve from time zero to infinity. | Up to 2 years 6 months | 
| Parts 3 and 4: Concentration Observed at the Last Timepoint Prior to Dosing (Ctrough) | Ctrough is defined as the concentration observed at the last timepoint prior to dosing. | Up to 2 years 6 months | 
| Parts 1, 2, 3, and 4: Presence of Anti-JNJ-63723283 Antibodies and Effect on Serum JNJ-63723283 Concentrations | Serum samples will be analyzed for antibodies to JNJ-63723283. The titer of the confirmed positive samples will be reported. | Up to 2 years 6 months | 
| Parts 1, 2, 3, and 4: Overall Response Rate (ORR) per Immune-Related Response Criteria (irRC) | ORR is defined as percentage of subjects with best objective response of complete response (CR) or partial response (PR) based on irRC criteria. | Up to 2 years 6 months | 
| Parts 1, 2, 3, and 4: Duration of Response (DOR) per RECIST v1.1 | 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. | Up to 2 years 6 months | 
| Parts 1, 2, 3, and 4: Duration of Response (DOR) per irRC | 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. | Up to 2 years 6 months | 
| Parts 1, 2, 3, and 4: Clinical Benefit Rate (CBR) per RECIST v1.1 | 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. | Up to 2 years 6 months | 
| Parts 1, 2, 3, and 4: Clinical Benefit Rate per irRC | 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. | Up to 2 years 6 months | 
| Parts 1, 2, 3, and 4: Progression-free Survival (PFS) per RECIST v1.1 | The time from first dose of JNJ-63723283 to progressive disease as defined by RECIST v 1.1 or death due to any cause. | Up to 2 years 6 months | 
| Parts 1, 2, 3, and 4: Progression-free Survival (PFS) per irRC | The time from first dose of JNJ-63723283 to progressive disease as defined by irRC or death due to any cause. | Up to 2 years 6 months | 
| Parts 1, 2, 3, and 4: Overall Survival (OS) | The time from first dose of JNJ-63723283 to death due to any cause. | Up to 2 years 6 months |