An Investigational Immuno-therapy Study for Safety of Nivolumab in Combination With Ipilimumab to Treat Advanced Cancers

Lung Cancer Clinical Trial

Official title:

A Phase 3b/4 Safety Trial of Flat Dose Nivolumab In Combination With Ipilimumab in Participants With Non-Small Cell Lung Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02869789
• Other study ID #: CA209-817
• Secondary ID: 2016-002621-10
• Status: Completed
• Phase: Phase 4
• Start date: October 5, 2016
• Est. completion date: May 13, 2022

Study information

• Verified date: June 2023
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A study to evaluate the safety of Nivolumab given in combination with Ipilimumab in patients with advanced cancers. The initial group will enroll patients with newly diagnosed Stage 4 or non-small cell lung cancer that has come back.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1041
• Est. completion date: May 13, 2022
• Est. primary completion date: May 13, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed Stage 4 or recurrent non-small cell lung cancer

• Eastern Cooperative Oncology Group (ECOG) score 0-1 (Physically able to carry out light housework or office work through to being fully active as you were before cancer)

• No prior systemic anticancer therapy (including EGFR and ALK inhibitors)

• Tissue or Programmed death-ligand 1 (PD-L1) results available

Cohort 1A Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) score 2 or

• Eastern Cooperative Oncology Group (ECOG) score 0-1 and one disease specific criteria as listed in the protocol

Cohort C Inclusion Criteria:

• High Tumor Mutation Burden

Exclusion Criteria:

• Untreated brain metastases

• An active malignancy that requires concurrent intervention

• Active, known or suspected autoimmune disease

• Carcinomatous meningitis, which means there is inflammation of the covering of the brain, caused by cancer

Other protocol-defined inclusion/exclusion criteria apply

Related Conditions & MeSH terms

• Lung Cancer
• Lung Neoplasms

Intervention

Drug:
• Nivolumab in combination with Ipilimumab
Specified dose on specified days

Locations

Country	Name	City	State
Argentina	Local Institution - 0007	Caba
Argentina	Local Institution - 0008	Capital Federal	Buenos Aires
Argentina	Local Institution - 0009	Cordoba
Argentina	Local Institution - 0126	Tucuman
Argentina	Local Institution - 0006	Viedma	RIO Negro
Belgium	Local Institution - 0038	Gent
Belgium	Local Institution - 0037	Liege
Belgium	Local Institution - 0036	Sint-Niklaas
Brazil	Local Institution - 0151	Barretos	Sao Paulo
Brazil	Local Institution - 0152	Ijui	RIO Grande DO SUL
Brazil	Local Institution - 0153	Porto Alegre	RIO Grande DO SUL
Brazil	Local Institution - 0154	Porto Alegre	RIO Grande DO SUL
Canada	Local Institution - 0127	Greenfield Park	Quebec
Canada	Local Institution - 0109	Montreal	Quebec
Canada	Local Institution - 0049	Rimouski	Quebec
Canada	Local Institution - 0050	Trois-Rivieres	Quebec
Chile	Local Institution - 0010	Santiago	Metropolitana
Chile	Local Institution - 0011	Santiago
Czechia	Local Institution - 0133	Novy Jicin
Czechia	Local Institution - 0130	Praha 2
France	Local Institution - 0118	Bordeaux
France	Local Institution - 0075	Dijon Cedex
France	Local Institution - 0069	Marseille Cedex 20
France	Local Institution - 0076	Paris
France	Local Institution - 0074	Pessac cedex
France	Local Institution - 0071	Rennes Cedex 9
France	Local Institution - 0070	Saint Herblain
France	Local Institution - 0072	Strasbourg Cedex
France	Local Institution - 0073	Toulon Cedex
Germany	Local Institution - 0023	Frankfurt
Germany	Local Institution - 0028	Gera
Germany	Local Institution - 0029	Kassel
Germany	Local Institution - 0026	Loewenstein
Germany	Local Institution - 0025	Wiesbaden
Greece	Local Institution - 0030	Athens
Greece	Local Institution - 0031	N. Faliro
Greece	Local Institution - 0032	Thessaloniki
Hungary	Local Institution - 0014	Budapest
Hungary	Local Institution - 0013	Gyöngyös - Mátraháza	Heves
Italy	Ospedale Policlinico San Martino	Genova
Italy	IRST Meldola	Meldola
Italy	Local Institution - 0054	Milan	Lombardia
Italy	AOU della Campania Luigi Vanvitelli	Napoli
Italy	Local Institution	Napoli
Italy	Ospedale Degli Infermi	Rimini
Italy	Azienda Ospedaliera Universitaria Senese	Siena
Italy	Azienda Ospedaliera Santa Maria Terni	Terni
Mexico	Local Institution - 0019	Monterrey, NL
Netherlands	Local Institution - 0045	Groningen
Netherlands	Local Institution - 0035	Rotterdam
Poland	Local Institution - 0015	Bydgoszcz
Poland	Local Institution - 0068	Sucha Beskidzka
Poland	Local Institution - 0016	Warszawa
Romania	Local Institution - 0128	Bucuresti
Romania	Local Institution - 0119	Craiova
Romania	Local Institution - 0120	Romania
Russian Federation	Local Institution - 0021	Moscow
Russian Federation	Local Institution - 0022	Moscow
Russian Federation	Local Institution - 0020	St Petersburg
Spain	Local Institution - 0061	A Coruña
Spain	Local Institution - 0060	Barcelona
Spain	Local Institution - 0062	Jaen
Spain	Local Institution - 0065	Madrid
Spain	Local Institution - 0064	Majadahonda - Madrid
Spain	Local Institution - 0063	Sevilla
Spain	Local Institution - 0059	Valencia
Spain	Local Institution - 0112	Zaragoza
Switzerland	Local Institution - 0048	Basel
Switzerland	Local Institution - 0046	Zuerich
Turkey	Local Institution - 0104	Antalya
United Kingdom	Local Institution - 0040	Edinburgh	Midlothian
United Kingdom	Local Institution - 0039	Leicester	Leicestershire
United Kingdom	Local Institution - 0041	London	Greater London
United Kingdom	Local Institution - 0043	Newcastle Upon Tyne
United Kingdom	Local Institution - 0042	Wirral
United States	Local Institution - 0139	Allentown	Pennsylvania
United States	Local Institution - 0163	Athens	Georgia
United States	Local Institution - 0002	Atlanta	Georgia
United States	Local Institution - 0166	Atlanta	Georgia
United States	Local Institution - 0090	Austin	Texas
United States	Local Institution - 0146	Bakersfield	California
United States	Local Institution - 0156	Belleville	New Jersey
United States	Local Institution - 0121	Birmingham	Alabama
United States	Local Institution - 0167	Bronx	New York
United States	Local Institution - 0123	Charleston	South Carolina
United States	Local Institution - 0066	Chattanooga	Tennessee
United States	Local Institution - 0100	Cincinnati	Ohio
United States	Local Institution - 0134	Cleveland	Ohio
United States	Local Institution - 0091	Columbia	Maryland
United States	Local Institution - 0172	Corvallis	Oregon
United States	Local Institution - 0149	Dallas	Texas
United States	Texas Oncology, P.A.	Dallas	Texas
United States	Local Institution - 0083	Denver	Colorado
United States	Local Institution - 0004	Durham	North Carolina
United States	Local Institution - 0089	Edina	Minnesota
United States	Local Institution - 0096	Eugene	Oregon
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	Local Institution - 0097	Fairfax	Virginia
United States	Summit Medical Group	Florham Park	New Jersey
United States	Local Institution - 0094	Fort Worth	Texas
United States	Local Institution - 0077	Grand Island	Nebraska
United States	Local Institution - 0141	Grand Junction	Colorado
United States	Marin Cancer Care, Inc	Greenbrae	California
United States	Jackson Oncology Associates, Pllc	Jackson	Mississippi
United States	Cancer Specialists of North FL	Jacksonville	Florida
United States	Local Institution - 0087	Las Vegas	Nevada
United States	Kentucky One Health St. Joseph East Cancer Center	Lexington	Kentucky
United States	Local Institution - 0164	Little Rock	Arkansas
United States	Local Institution - 0142	Livingston	New Jersey
United States	Local Institution - 0093	Longview	Texas
United States	Local Institution - 0115	Los Angeles	California
United States	Los Angeles Hematology/Oncology Medical Group	Los Angeles	California
United States	Local Institution - 0067	Nashville	Tennessee
United States	Local Institution - 0088	Niles	Illinois
United States	Local Institution - 0082	Ocala	Florida
United States	Local Institution - 0147	Pembroke Pines	Florida
United States	Local Institution - 0148	Phoenix	Arizona
United States	Allegheny Health Network	Pittsburgh	Pennsylvania
United States	Local Institution - 0159	Pittsburgh	Pennsylvania
United States	Local Institution - 0098	Plano	Texas
United States	Local Institution - 0176	Portland	Oregon
United States	Torrance Health Association	Redondo Beach	California
United States	Local Institution - 0170	Reno	Nevada
United States	Local Institution - 0174	Renton	Washington
United States	Local Institution - 0044	Richmond	Virginia
United States	Va San Diego Healthcare System	San Diego	California
United States	Local Institution - 0143	San Luis Obispo	California
United States	Local Institution - 0144	Santa Maria	California
United States	Local Institution - 0001	Sayre	Pennsylvania
United States	Local Institution - 0173	Spokane	Washington
United States	Gene Upshaw Memorial Tahoe Forest Cancer Center	Truckee	California
United States	Local Institution - 0085	Tucson	Arizona
United States	Local Institution - 0086	Waco	Texas
United States	Local Institution - 0161	Whittier	California
United States	Local Institution - 0108	Wichita	Kansas
United States	Local Institution - 0012	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Canada,  Chile,  Czechia,  France,  Germany,  Greece,  Hungary,  Italy,  Mexico,  Netherlands,  Poland,  Romania,  Russian Federation,  Spain,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs)	Drug related AEs are those events with relationship to study drug. If the relationship to study drug is missing, the AE will be considered as drug-related. The select AEs of interest are the following: Pulmonary, Renal, Gastrointestinal, Hepatic, Skin, Endocrine, and hypersensitivity/infusion reaction events. AEs are reported using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.; Grade 3= Prolonged severe reaction Grade 4= Life threatening Grade 5= Death	From first dose to 30 days post last dose (Up to approximately 27 months)
Primary	Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs)	imAEs are specific events that include pneumonitis, diarrhea/colitis, hepatitis, nephritis/renal dysfunction, rash, and endocrine (adrenal insufficiency, hypothyroidism/thyroiditis, hyperthyroidism, diabetes mellitus, and hypophysitis). AEs are reported using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.; Grade 3= Prolonged severe reaction Grade 4= Life threatening Grade 5= Death	From first dose to 100 days post last dose (Up to approximately 29 months)
Secondary	Progression Free Survival (PFS)	PFS is defined as the time from first dosing date to the date of the first documented tumor progression, as determined by investigators (per RECIST v1.1), or death due to any cause, whichever occurs first.; Progressive Disease (PD)= = 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The sum must also demonstrate an absolute increase of = 5 mm. The appearance of one or more new lesions is also considered progression.	From first dosing date to the date of first documented tumor progression or, death due to any cause, whichever occurs first (Up to approximately 67 months)
Secondary	Overall Survival (OS)	OS is defined as the time from first dosing date to the date of death. A participant who has not died will be censored at last known date alive.	From first dosing date to the date of death (Up to approximately 67 months)
Secondary	Objective Response Rate (ORR)	ORR is defined as the percentage of participants with a best overall response of confirmed complete response (CR) or partial response (PR).; CR= Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.; PR= = 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	From first dosing date up to approximately 67 months
Secondary	Duration of Response (DoR)	DoR is defined as the time between the date of first confirmed complete response (CR) or partial response (PR) to the date of the first documented tumor progression per RECIST 1.1, or death due to any cause, whichever occurs first.; CR= Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.; PR= = 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.; Progressive Disease (PD)= = 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The sum must also demonstrate an absolute increase of = 5 mm. The appearance of one or more new lesions is also considered progression.	From first dosing date to the date of first documented tumor progression or, death due to any cause, whichever occurs first (Up to approximately 67 months)
Secondary	Change From Baseline in Health-Related Quality of Life (HRQoL) Using Functional Assessment of Cancer Therapy-Lung (FACT-L)	FACT-L is a quality-of-life questionnaire which includes Lung Cancer Subscale (LCS) that assesses the treatment impact on lung cancer related symptoms in 5 domains: Physical, social/family, emotional, and functional well-being using a 5-point scale (0=not at all; 1=a little bit, 2=somewhat; 3=quite a bit; 4=very much) added to obtain total score. The ranges of possible total scores are 0-136 for the FACT-L with a higher score representing better quality of life, improved symptomatology and enhanced physical/functional outcomes. According to Functional Assessment of Chronic Illness Therapy scoring guidelines, in the event of missing responses for some of the questions, scores will be prorated using the average of the other answers in that scale.; Baseline is defined as events that occur before the date/time of first dose. Post treatment visits include follow-up (FU) visit 1, FU visit 2, and subsequent survival FU visits to occur every 3 months up until survival FU visit 18.	From baseline and up to subsequent survival follow-up visit 18 (Up to approximately 67 months)

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting