Clinical trial NCT02659059: Nivolumab in Combination With Ipilimumab (Part 1); Nivolumab Plus Ipilimumab in Combination With Chemotherapy (Part 2) as First Line Therapy in Stage IV Non-Small Cell Lung Cancer
Official title: A Study of Nivolumab in Combination With Ipilimumab (Part 1); and Nivolumab Plus Ipilimumab in Combination With Chemotherapy (Part 2) as First Line Therapy in Stage IV Non-Small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Small-Cell Lung Cancer
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2016-01-20
Enrollment: 324
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of part 1 of this study is to determine the objective response rate (ORR) in stage IV NSCLC subjects treated with nivolumab in combination with ipilimumab as first line therapy.

The purpose of part 2 of this study is to determine the safety and tolerability of nivolumab and ipilimumab combined with a short course of chemotherapy in first line stage IV NSCLC.


Eligibility criteria: Inclusion Criteria:

* Men and Women ≥ 18 years of age
* Diagnosed with stage IV Non-Small Cell Lung Cancer
* Diagnosed with recurrent stage IIIB non-small cell lung cancer and failed previous concurrent chemoradiation with no further curative options.

Exclusion Criteria:

* Subjects with untreated CNS metastases are excluded.
* Subjects with carcinomatous meningitis
* Subjects with an active, known or suspected autoimmune disease.
* Subjects with a condition requiring systemic treatment with either corticosteroids ( \> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first treatment.
* Women who are pregnant, plan to become pregnant, and/or breastfeed during the study.

Other protocol defined inclusion/exclusion criteria apply

Primary outcomes:
measure: Objective Response Rate (ORR) by PD-L1 Positive and Negative Levels - Part 1
timeFrame: From first dose to database lock (Up to 18 months)
measure: Number of Participants With Dose Limiting Toxicities (DLTs) - Part 2
timeFrame: 9 weeks after first dose
measure: Number of Participants With Adverse Events (AEs) - Part 2
timeFrame: Deaths are from first dose to database lock (Up to 24 months). AEs and SAEs are from first dose to 30 days post last dose
measure: Number of Participants With Laboratory Abnormalities in Hepatic Tests - Part 2
timeFrame: From first dose to 30 days post last dose
measure: Number of Participants With Laboratory Abnormalities in Thyroid Tests - Part 2
timeFrame: From first dose to 30 days post last dose
Secondary outcomes:
measure: Overall Survival (OS) - Part 1
timeFrame: From the date of first treatment to the date of death due to any cause (Up to approximately 72 months)
measure: Overall Survival (OS) - Part 2
timeFrame: From the date of first treatment to the date of death due to any cause (Up to approximately 59 months)
measure: Progression Free Survival (PFS) - Part 1
timeFrame: From first dose to the first date of documented progression, or death due to any cause, whichever occurred first (Up to approximately 72 months)
measure: Progression Free Survival (PFS) - Part 2
timeFrame: From first dose to the first date of documented progression, or death due to any cause, whichever occurred first (Up to approximately 59 months)
measure: Objective Response Rate (ORR) - Part 1
timeFrame: From first dose up to approximately 72 months
measure: Objective Response Rate (ORR) - Part 2
timeFrame: From first dose up to approximately 59 months
measure: Overall Survival (OS) by PD-L1 Expression Levels - Part 1
timeFrame: From the date of first treatment to the date of death due to any cause (Up to approximately 72 months)
measure: Progression Free Survival (PFS) by PD-L1 Expression Levels - Part 1
timeFrame: From first dose to the first date of documented progression, or death due to any cause, whichever occurred first (Up to approximately 72 months)
measure: Objective Response Rate (ORR) by PD-L1 Expression Levels-Part 1
timeFrame: From first dose up to approximately 72 months
measure: Overall Survival (OS) by Tumor Mutation Burden (TMB) Levels - Part 1
timeFrame: From the date of first treatment to the date of death due to any cause (Up to approximately 72 months)
measure: Progression Free Survival (PFS) by Tumor Mutation Burden (TMB) Levels - Part 1
timeFrame: From first dose to the first date of documented progression, or death due to any cause, whichever occurred first (Up to approximately 72 months)
measure: Objective Response Rate (ORR) by Tumor Mutation Burden (TMB) Levels - Part 1
timeFrame: From first dose up to approximately 72 months
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: Plainville
country: United States
facility: Cancer Center Of Central Connecticut
state: Connecticut
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute.
state: Georgia
city: Savannah
country: United States
facility: Summit Cancer Care
state: Georgia
city: Wichita
country: United States
facility: Cancer Center Of Kansas
state: Kansas
city: Louisville
country: United States
facility: University Of Louisville Medical Center, Inc., Dba
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Cancer Center
state: Maryland
city: Boston
country: United States
facility: Local Institution - 0029
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 0030
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Lincoln
country: United States
facility: Local Institution - 0015
state: Nebraska
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: Local Institution - 0036
state: New Mexico
city: Albuquerque
country: United States
facility: Lovelace Cancer Care
state: New Mexico
city: Albuquerque
country: United States
facility: New Mexico Cancer Care Alliance
state: New Mexico
city: Albuquerque
country: United States
facility: New Mexico Cancer Care Center
state: New Mexico
city: Albuquerque
country: United States
facility: The Cancer Center at Presbyterian
state: New Mexico
city: Mineola
country: United States
facility: Local Institution - 0010
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Nassau
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Winston-Salem
country: United States
facility: Novant Health Oncology Specialists
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Local Institution - 0006
state: Pennsylvania
city: Charleston
country: United States
facility: Charleston Hematology Oncology Associates, Pa
state: South Carolina
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC - SCRI - PPDS
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Kingston
country: Canada
facility: Local Institution - 0022
state: Ontario
city: Sault Ste Marie
country: Canada
facility: Local Institution - 0023
state: Ontario
city: St. Jerome
country: Canada
facility: Csss De St-Jerome
state: Quebec
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Ready N, Hellmann MD, Awad MM, Otterson GA, Gutierrez M, Gainor JF, Borghaei H, Jolivet J, Horn L, Mates M, Brahmer J, Rabinowitz I, Reddy PS, Chesney J, Orcutt J, Spigel DR, Reck M, O'Byrne KJ, Paz-Ares L, Hu W, Zerba K, Li X, Lestini B, Geese WJ, Szustakowski JD, Green G, Chang H, Ramalingam SS. First-Line Nivolumab Plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer (CheckMate 568): Outcomes by Programmed Death Ligand 1 and Tumor Mutational Burden as Biomarkers. J Clin Oncol. 2019 Apr 20;37(12):992-1000. doi: 10.1200/JCO.18.01042. Epub 2019 Feb 20.