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

• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Study Description

Brief Summary:

The Primary purpose of this study is to identify the recommended Phase 2 dose [RP2D(s)] for JNJ-63723283 in Part 1 and 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.

Condition or disease	Intervention/treatment	Phase
Neoplasms	Drug: JNJ-63723283	Phase 1; Phase 2

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]) for JNJ-63723283 in Part 1 and to evaluate the safety and efficacy of the RP2D(s) in Part 2. Subject 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 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 Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	250 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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
Actual Study Start Date :	November 2016
Estimated Primary Completion Date :	April 2019
Estimated Study Completion Date :	December 2019

Arms and Interventions

Arm

Intervention/treatment

Experimental: JNJ-63723283; 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.

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

Outcome Measures

Primary Outcome Measures :

1. Frequency and Severity of Dose-Limiting Toxicity (DLT) [ Time Frame: Approximate 2.5 years ]
2. Overall Response Rate (ORR) per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in Subjects With Selected Advanced Solid Tumors [ Time Frame: Approximate 2.5 years ]
   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.

Secondary Outcome Measures :

1. Number of Participants With Adverse Events as a Measure of Safety [ Time Frame: Approximate 2.5 years ]
2. Maximum Observed Serum Concentration (Cmax) [ Time Frame: Approximate 2.5 years ]
   The Cmax is the maximum observed serum concentration.
3. Area Under the Concentration-Time Curve Between t1 and t2 (AUCt1-t2) [ Time Frame: Approximate 2.5 years ]
4. Elimination Half-Life (t1/2) [ Time Frame: Approximate 2.5 years ]
   The elimination half-life (t1/2) is the time measured for the serum concentration to decrease by 1 half to its original concentration.
5. Total Systemic Clearance of (CL) [ Time Frame: Approximate 2.5 years ]
   Systemic Clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the body.
6. Volume of Distribution at Steady-State (Vss) [ Time Frame: Approximate 2.5 years ]
   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.
7. Accumulation Ratio (R) [ Time Frame: Approximate 2.5 years ]
   The R is obtained by dividing AUC at two different time points.
8. Presence of Anti-JNJ-63723283 Antibodies and Effect on Serum JNJ-63723283 Concentrations [ Time Frame: Approximate 2.5 years ]
   Serum samples will be screened for antibodies binding to JNJ-63723283. The titer of confirmed positive samples will be reported.
9. Overall Response Rate (ORR) per Immune-Related Response Criteria (irRC) [ Time Frame: Approximate 2.5 years ]
   ORR is defined as percentage of subjects with best objective response of complete response (CR) or partial response (PR) based on irRC criteria.
10. Duration of Response (DOR) per RECIST v1.1 [ Time Frame: Approximate 2.5 years ]
    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.
11. Duration of Response (DOR) per irRC [ Time Frame: Approximate 2.5 years ]
    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.
12. Clinical Benefit Rate (CBR) per RECIST v1.1 [ Time Frame: Approximate 2.5 years ]
    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.
13. Clinical Benefit Rate per irRC [ Time Frame: Approximate 2.5 years ]
    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.
14. Progression-free Survival (PFS) per RECIST v1.1 [ Time Frame: Approximate 2.5 years ]
    The time from first dose of JNJ-63723283 to progressive disease as defined by RECIST v 1.1 or death due to any cause.
15. Progression-free Survival (PFS) per irRC [ Time Frame: Approximate 2.5 years ]
    The time from first dose of JNJ-63723283 to progressive disease as defined by irRC or death due to any cause.
16. Overall Survival (OS) [ Time Frame: Approximate 2.5 years ]
    The time from first dose of JNJ-63723283 to death due to any cause.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Contacts

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Contact: Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions:		JNJ.CT@sylogent.com

Locations

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United States, Missouri
Washington University School of Medicine	Recruiting
Saint Louis, Missouri, United States, 63110
United States, Pennsylvania
UPMC Cancer Centers	Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Italy
Ospedali Riuniti Di Ancona	Active, not recruiting
Ancona, Italy, 60126
Ospedale San Giuseppe Moscati di Avellino	Withdrawn
Avellino, Italy, 83100
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori	Active, not recruiting
Meldola, Italy, 47014
Istituto Europeo di Oncologia Servizio Radioterapia	Recruiting
Milano, Italy, 20141
San Gerardo Hospital	Active, not recruiting
Monza, Italy, 20052
IRCCS-Fondazione Pascale	Active, not recruiting
Napoli, Italy, 80131
Aou San Luigi Gonzaga	Completed
Orbassano, Italy, 10043
Istituto Clinico Humanitas	Withdrawn
Rozzano, Italy, 20089
Azienda Ospedaliera Universitaria Senese	Completed
Siena, Italy, 53100
Poland
Uniwersytecki Szpital Kliniczny w Bialymstoku, II Klinika Chorob Pluc i Gruzlicy	Recruiting
Bialystok, Poland, 15-540
CO-I im. Sklodowskiej-Curie, Klinika Nowotworow Pluca i Klatki Piersiowej	Recruiting
Warszawa, Poland, 02-781
CO-I im. Sklodowskiej-Curie, Klinika Nowotworow Tkanek Miekkich, Kosci i Czerniakow	Recruiting
Warszawa, Poland, 02-781
Russian Federation
FSBSI 'N. N. Blokhin Russian Cancer Research Center'	Active, not recruiting
Moscow, Russian Federation, 115478
Pyatigorsky Oncology Dispensary	Active, not recruiting
Pyatigorsk, Russian Federation, 357502
BioEk, LLC	Completed
St. Petersburg, Russian Federation, 197342
City Oncology Dispensary	Completed
St. Petersburg, Russian Federation, 198255
City Oncology Dispensary	Active, not recruiting
St. Petersburg, Russian Federation, 198255
Spain
Hosp. Univ. Germans Trias I Pujol	Completed
Badalona, Spain, 8916
Hosp. Univ. Vall D Hebron	Recruiting
Barcelona, Spain, 8035
Hosp. Gral. Univ. Gregorio Maranon	Recruiting
Madrid, Spain, 28009
Hosp. Univ. Fund. Jimenez Diaz	Recruiting
Madrid, Spain, 28040
Hosp. Univ. 12 de Octubre	Recruiting
Madrid, Spain, 28041
Hosp. Univ. Hm Sanchinarro	Recruiting
Madrid, Spain, 28050
Hosp. Virgen de La Victoria	Recruiting
Malaga, Spain, 29010
Clinica Univ. de Navarra	Recruiting
Pamplona, Spain, 31008
Hosp. Virgen Del Rocio	Recruiting
Sevilla, Spain, 41013
Hosp. Clinico Univ. de Valencia	Recruiting
Valencia, Spain, 46010
United Kingdom
Beatson West Of Scotland Cancer Centre	Recruiting
Glasgow, United Kingdom, G12 0YN
Sarah Cannon Research Institute	Recruiting
London, United Kingdom, W1G 6AD
The Christie Nhs Foundation Trust	Recruiting
Manchester, United Kingdom, M20 4BX
Sir Bobby Robson Unit, Northern Centre for Cancer Care	Recruiting
Newcastle Upon Tyne, United Kingdom, NE7 7DN

Sponsors and Collaborators

Janssen Research & Development, LLC

Investigators

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Study Director:	Janssen Research & Development, LLC Clinical Trial	Janssen Research & Development, LLC

More Information

Additional Information:

To learn how to participate in this trial please click here. 

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Responsible Party:	Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:	NCT02908906 History of Changes
Other Study ID Numbers:	CR108223; 2016-002017-22 ( EudraCT Number ); 63723283LUC1001 ( Other Identifier: Janssen Research & Development, LLC )
First Posted:	September 21, 2016
Last Update Posted:	March 1, 2019
Last Verified:	February 2019

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Studies a U.S. FDA-regulated Device Product:		No

Additional relevant MeSH terms:

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Antibodies; Antibodies, Monoclonal; Immunologic Factors; Physiological Effects of Drugs