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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Neoplasms
• Intervention / Treatment: Drug: JNJ-63723283

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, to determine a SC RP2D in Part 3 and Part 4 and to evaluate JNJ-63723283 SC administration PK compared to JNJ-63723283 IV administration in Part 5. 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 Parts 1, 2 and 5) 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 Type: Interventional
• Enrollment (Actual): 413
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Study Contact; Email: Participate-In-This-Study@its.jnj.com

Study Locations

• Moldova, Republic of
  • Chisinau, Moldova, Republic of
• Poland
  • Bialystok, Poland
  • Warszawa, Poland
• Russian Federation
  • Moscow, Russian Federation
  • Pyatigorsk, Russian Federation
  • St. Petersburg, Russian Federation
• Spain
  • Badalona, Spain
  • Barcelona, Spain
  • Madrid, Spain
  • Malaga, Spain
  • Pamplona, Spain
  • Sevilla, Spain
  • Valencia, Spain
• Sweden
  • Goteborg, Sweden
• United Kingdom
  • Glasgow, United Kingdom
  • London, United Kingdom
  • Manchester, United Kingdom
  • Newcastle upon Tyne, United Kingdom
• United States
  • Missouri
    • Saint Louis, Missouri, United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: JNJ-63723283; 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; JNJ-63723283 will be administered by IV infusion or SC injection or infusion.; Other Names: Cetrelimab

What is the study measuring?

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 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 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 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

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Felip E, Moreno V, Morgensztern D, Curigliano G, Rutkowski P, Trigo JM, Calvo A, Kowalski D, Cortinovis D, Plummer R, Maio M, Ascierto PA, Vladimirov VI, Cervantes A, Zudaire E, Hazra A, T'jollyn H, Bandyopadhyay N, Greger JG, Attiyeh E, Xie H, Calvo E. First-in-human, open-label, phase 1/2 study of the monoclonal antibody programmed cell death protein-1 (PD-1) inhibitor cetrelimab (JNJ-63723283) in patients with advanced cancers. Cancer Chemother Pharmacol. 2022 Apr;89(4):499-514. doi: 10.1007/s00280-022-04414-6. Epub 2022 Mar 17.

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2016
• Primary Completion (Actual): November 17, 2023
• Study Completion (Estimated): October 24, 2025

Study Registration Dates

• First Submitted: September 19, 2016
• First Submitted That Met QC Criteria: September 19, 2016
• First Posted (Estimated): September 21, 2016

Study Record Updates

• Last Update Posted (Actual): April 25, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: CR108223; 2016-002017-22 (EudraCT Number); 63723283LUC1001 (Other Identifier: Janssen Research & Development, LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: No