A Study of Nivolumab and Ipilimumab in Untreated Participants With Stage 3 Non-small Cell Lung Cancer (NSCLC) That is Unable or Not Planned to be Removed by Surgery

Phase 3

Completed

Conditions: Non-Small Cell Lung Cancer (NSCLC)

Interventions: Biological: durvalumab
Biological: nivolumab
Biological: ipilimumab

Registration Number: NCT04026412

Lead Sponsor: Bristol-Myers Squibb

Brief Summary: The primary purpose of the study is to compare the effectiveness of nivolumab plus concurrent chemoradiotherapy (CCRT) followed by nivolumab plus ipilimumab vs CCRT followed by durvalumab in participants with untreated Locally Advanced Non-small Cell Lung Cancer (LA NSCLC).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 925

Inclusion Criteria

Eastern Cooperative Oncology Group (ECOG) performance status ≤1
Locally advanced stage IIIA, IIIB, or IIIC (T1-2 N2-3 M0, T3 N1-3 M0, or T4 N0-3 M0) pathologically-confirmed NSCLC, according to 8th TNM classification. Participants who are not planned for potential curative surgical resection are eligible.
Newly diagnosed and treatment-naïve, with no prior local or systemic anticancer therapy given as primary therapy for locally advanced disease

Exclusion Criteria

Any condition including medical, emotional, psychiatric, or logistical that, in the opinion of the Investigator would preclude the participant from adhering to the protocol or would increase the risk associated with study participation
Active infection requiring systemic therapy within 14 days prior to randomization
History of organ or tissue transplant that requires systemic use of immune suppressive agents
Prior thoracic radiotherapy

Other protocol-defined inclusion/exclusion criteria apply

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm C: CCRT + durvalumab	durvalumab	Concurrent chemoradiotherapy (CCRT)
Arm A: nivolumab + CCRT + ipilimumab	nivolumab	Concurrent chemoradiotherapy (CCRT)
Arm A: nivolumab + CCRT + ipilimumab	ipilimumab	Concurrent chemoradiotherapy (CCRT)
Arm B: nivolumab + CCRT	nivolumab	Concurrent chemoradiotherapy (CCRT)

Primary Outcome Measures

Name	Time	Method
Arm A Vs Arm C - Progression-Free Survival (PFS) by RECIST 1.1 Per Blinded Independent Central Review (BICR)	From randomization untill disease progression or death, whichever occurs first (up to approximately 53 months)	Progression-Free Survival then (PFS) is defined as the time between the date of randomization and the date of first documented disease progression, based on BICR assessments (per RECIST v1.1), or death due to any cause, whichever occurs first based on Kaplan-Meier estimates. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	From randomization untill death (up to approximately 61 months)	Overall Survival (OS) for all randomized participants is the time between randomization and the date of death from any cause based on Kaplan-Meier estimates. For participants who are alive, their survival time was censored at the last date that they were known to be alive. OS was censored for participants at the date of randomization if they had no follow-up.
Arm B Vs Arm C and Arm A Vs Arm B- Progression-Free Survival (Irrespective of Subsequent Therapy) by RECIST 1.1 Per Blinded Independent Central Review (BICR)	From randomization untill disease progression or death, whichever occurs first (up to approximately 61 months)	Progression-Free Survival (PFS) is defined as the time between the date of randomization and the date of first documented disease progression, based on BICR assessments (per RECIST v1.1), or death due to any cause, whichever occurs first based on Kaplan-Meier estimates. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Objective Response Rate (ORR) by BICR	From randomization untill disease progression or death, whichever occurs first (up to approximately 61 months)	Objective Response Rate (ORR) is defined as the percentage of participants whose best overall response (BOR) is either CR or PR by blinded independent central review (BICR) per response evaluation criteria in solid tumors (RECIST) v1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Duration of Response (DoR) by RECIST 1.1 Per BICR	From randomization untill disease progression or death, whichever occurs first (up to approximately 61 months)	Duration of objective response (DoR) is defined as the time between the date of first confirmed response (CR or PR) to the date of the first documented tumor progression (per RECIST 1.1) per BICR assessment, or death due to any cause, whichever occurs first. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time to Response (TTR) by RECIST 1.1 Per BICR	From randomization untill disease progression or death, whichever occurs first (up to approximately 61 months)	Time to response (TTR) is defined as the time, in months, from randomization to the first objective documentation of PR or better assessed per BICR. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.
Progression Free Survival (PFS) by RECIST 1.1 Per Investigator Assessment	From randomization untill disease progression or death, whichever occurs first (up to approximately 61 months)	Progression-Free Survival then (PFS) is defined as the time between the date of randomization and the date of first documented disease progression, based on Investigator assessments (per RECIST v1.1), or death due to any cause, whichever occurs first Calculated using Kaplan-Meier estimates. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Objective Response Rate (ORR) by RECIST 1.1 Per Investigator Assessment	From randomization untill disease progression or death, whichever occurs first (up to approximately 61 months)	ORR is defined as the percentage of participants whose best overall response (BOR) is either CR or PR by investigator assessment per response evaluation criteria in solid tumors (RECIST) v1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Duration of Response (DOR) by RECIST 1.1 Per Investigator Assessment	From randomization untill disease progression or death, whichever occurs first (up to approximately 61 months)	Duration of objective response (DoR) is defined as the time between the date of first confirmed response (CR or PR) to the date of the first documented tumor progression (per RECIST 1.1) per investigator assessment, or death due to any cause, whichever occurs first. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time to Response (TTR) by RECIST 1.1 Per Investigator Assessment	From randomization untill disease progression or death, whichever occurs first (up to approximately 61 months)	Time to response (TTR) is defined as the time, in months, from randomization to the first objective documentation of PR or better assessed per investigator assessment. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time to Death or Distant Metastases (TDDM)	From randomization until metastases or death, whichever occurs first (up to approximately 61 months)	Time to Death or Distant Metastases (TDDM) is defined as the time from the date of randomization until the first date of distant metastasis or death in the absence of distant metastasis based on Kaplan-Meier estimates. Distant metastasis is defined as any new lesion that is outside of the thorax (except for heart) according to RECIST 1.1, as assessed by the Investigator.
Number of Participants With Adverse Events (AEs), Serious AEs and Select AEs	From first dose (Day 1) till 30 days after the last dose (up to approximately 19 months)	An Adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the use of medicinal product, whether or not considered related to the investigational medicinal product. A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose results in death, is life-threatening (defined as an event in which the subject was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe), requires inpatient hospitalization or causes prolongation of existing hospitalization.
Change From Baseline in Non-small Cell Lung Cancer (NSCLC)-Symptom Assessment Questionnaire (SAQ) Total Score at Week 48	Baseline (Day 1) and Week 48	The NSCLC-SAQ is a questionnaire used in clinical trials to understand how non-small cell lung cancer (NSCLC) affects your daily life and well-being. It has 7 questions that ask about your symptoms over the past 7 days, including cough, pain, shortness of breath, fatigue, and appetite loss. The total scores from the questionnaire range from 0 to 20. A higher score means you have more severe symptoms and are feeling worse, which is a bad outcome. A lower score means you have fewer symptoms and are feeling better, which is a good outcome.

Trial Locations

Locations (179): Local Institution - 0119
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La Jolla, California, United States
Local Institution - 0207
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San Francisco, California, United States
Local Institution - 0166
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San Francisco, California, United States
Local Institution - 0129
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Lone Tree, Colorado, United States
Local Institution - 0233
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Jacksonville, Florida, United States
Local Institution - 0219
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Orlando, Florida, United States
Local Institution - 0039
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Pensacola, Florida, United States
Local Institution - 0125
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Atlanta, Georgia, United States
Local Institution - 0165
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Augusta, Georgia, United States
Local Institution - 0218
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Edgewood, Kentucky, United States
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Local Institution - 0119
🇺🇸La Jolla, California, United States