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

Neoplasms Clinical Trial

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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02908906
• Other study ID #: CR108223
• Secondary ID: 2016-002017-2263
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: November 21, 2016
• Est. completion date: October 24, 2025

Study information

• Verified date: June 2024
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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, to determine one or more additional RP2Ds in Parts 3 and 4.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 413
• Est. completion date: October 24, 2025
• Est. primary completion date: November 17, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms

Intervention

Drug:
• JNJ-63723283
JNJ-63723283 will be administered by IV infusion or SC injection or infusion.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Moldova, Republic of,  Poland,  Russian Federation,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Parts 3 and 4: Average Concentration (Cavg) of JNJ-63723283	Cavg of JNJ-63723283 will be reported.	Up to 2 years 6 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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