Clinical trial NCT02908906: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Neoplasms
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2016-09-21
Enrollment: 413
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Part 1: Frequency and Severity of Dose-Limiting Toxicity (DLT)
timeFrame: Up to 2 years 6 months
measure: Part 2: Overall Response Rate (ORR) per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in Subjects With Selected Advanced Solid Tumors
timeFrame: Up to 2 years 6 months
measure: Parts 3 and 4: Area Under the Serum Concentration Versus Time Curve from Time Zero to Dosing Interval (AUC [0-tau])
timeFrame: Up to 2 years 6 months
Secondary outcomes:
measure: Parts 1, 2, 3, and 4 : Number of Participants With Adverse Events (AEs) as a Measure of Safety
timeFrame: Up to 2 years 6 months
measure: Parts 1, 2 and 3, and 4: Maximum Observed Serum Concentration (Cmax)
timeFrame: Up to 2 years 6 months
measure: Parts 1 and 2: Area Under the Serum Concentration Versus Time Curve Between time t1 and t2 (AUC [t1-t2])
timeFrame: Up to 2 years 6 months
measure: Parts 1, 2 and 3: Elimination Half-Life (t1/2)
timeFrame: Up to 2 years 6 months
measure: Parts 1 and 2: Total Systemic Clearance of (CL)
timeFrame: Up to 2 years 6 months
measure: Parts 1 and 2: Volume of Distribution at Steady-State (Vss)
timeFrame: Up to 2 years 6 months
measure: Parts 1 and 2: Accumulation Ratio (R)
timeFrame: Up to 2 years 6 months
measure: Parts 3 and 4: Average Concentration (Cavg) of JNJ-63723283
timeFrame: Up to 2 years 6 months
measure: Parts 3 and 4: Area Under the Serum Concentration Versus Time Curve Between Time Zero and Time t (AUC [0-t])
timeFrame: Up to 2 years 6 months
measure: Parts 3: Area Under the Serum Concentration Versus Time Curve from Time Zero to Infinity (AUC [0-Infinity])
timeFrame: Up to 2 years 6 months
measure: Parts 3 and 4: Concentration Observed at the Last Timepoint Prior to Dosing (Ctrough)
timeFrame: Up to 2 years 6 months
measure: Parts 1, 2, 3, and 4: Presence of Anti-JNJ-63723283 Antibodies and Effect on Serum JNJ-63723283 Concentrations
timeFrame: Up to 2 years 6 months
measure: Parts 1, 2, 3, and 4: Overall Response Rate (ORR) per Immune-Related Response Criteria (irRC)
timeFrame: Up to 2 years 6 months
measure: Parts 1, 2, 3, and 4: Duration of Response (DOR) per RECIST v1.1
timeFrame: Up to 2 years 6 months
measure: Parts 1, 2, 3, and 4: Duration of Response (DOR) per irRC
timeFrame: Up to 2 years 6 months
measure: Parts 1, 2, 3, and 4: Clinical Benefit Rate (CBR) per RECIST v1.1
timeFrame: Up to 2 years 6 months
measure: Parts 1, 2, 3, and 4: Clinical Benefit Rate per irRC
timeFrame: Up to 2 years 6 months
measure: Parts 1, 2, 3, and 4: Progression-free Survival (PFS) per RECIST v1.1
timeFrame: Up to 2 years 6 months
measure: Parts 1, 2, 3, and 4: Progression-free Survival (PFS) per irRC
timeFrame: Up to 2 years 6 months
measure: Parts 1, 2, 3, and 4: Overall Survival (OS)
timeFrame: Up to 2 years 6 months
Other outcomes:
Locations:
city: Saint Louis
country: United States
state: Missouri
city: Pittsburgh
country: United States
state: Pennsylvania
city: Chisinau
country: Moldova, Republic of
city: Bialystok
country: Poland
city: Warszawa
country: Poland
city: Moscow
country: Russian Federation
city: Pyatigorsk
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Badalona
country: Spain
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Malaga
country: Spain
city: Pamplona
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
city: Goteborg
country: Sweden
city: Glasgow
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Newcastle upon Tyne
country: United Kingdom
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.