A Dose Frequency Optimization,Trial of Nivolumab 240 mg Every 2 Weeks vs Nivolumab 480 mg Every 4 Weeks in Subjects With Advanced or Metastatic Non-small Cell Lung Cancer Who Received Up to 12 Months of Nivolumab at 3 mg/kg or 240 mg Every 2 Weeks

Phase 3

Completed

Conditions: Lung Cancer

Registration Number: NCT02713867

Lead Sponsor: Bristol-Myers Squibb

Brief Summary: The primary objective of this study is to compare PFS (progression-free survival) rate at 6 months and at 1 year after randomization, of Nivolumab 480 mg every 4 weeks with nivolumab 240 mg every 2 weeks in subjects with advanced/metastatic (Stage IIIb/IV) NSCLC (non-Sq and Sq).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 363

Inclusion Criteria

Histologically or cytologically documented Squamous or non-Squamous Non-small cell lung cancer (NSCLC) (Stage IIIB/IV), or recurrent or progressive disease following multimodal therapy
Patients must have received pre-study nivolumab for up to 12 months and have 2 consecutive tumor assessments confirming Complete response (CR), Partial response (PR), or Stable disease (SD)
Measurable disease before start of pre-study nivolumab treatment
Eastern Cooperative Oncology Group (ECOG) Performance status (PS) 0-2

Exclusion Criteria

Carcinomatous meningitis
Untreated, symptomatic Central nervous system (CNS) metastases
Symptomatic interstitial lung disease

Other protocol defined inclusion/exclusion criteria could apply

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Progression Free Survival Rate (PFSR) at 6 Months	At 6 Months	The proportion of participants remaining progression free and surviving at 6 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on 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. Note: the appearance of one or more new lesions is also considered progression.
Progression Free Survival Rate (PFSR) at 12 Months	At 12 Months	The proportion of participants remaining progression free and surviving at 6 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on 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. Note: the appearance of one or more new lesions is also considered progression.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS) Rate at 12 Months	At 12 Months	The proportion of participants alive at 12 months. OS is defined as time from the date of randomization to the date of death. Participants who did not die by the end of the study will be censored at the last known date alive.
Overall Survival (OS) Rate up to 60 Months	From randomization to the date of death, Up to 60 Months	The proportion of participants alive up to 60 months. OS is defined as time from the date of randomization to the date of death. Participants who did not die by the end of the study will be censored at the last known date alive.
Overall Survival Rate by Response Criteria at 12 Months	12 Months	The proportion of participants alive at 12 months. OS is defined as time from the date of randomization to the date of death. Participants who did not die by the end of the study will be censored at the last known date alive. 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. Stable Disease (SD): Neither sufficient shrinkage from the baseline study to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. OS rate by response did not have data collected after 12 months randomization.
Percentage of Participants With an Adverse Events (AEs)	Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months)	Percentage of participants with an Adverse Event due to any cause An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment.
Percentage of Participants With an Adverse Events Leading to Discontinuation (AEsDC)	Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months)	Percentage of Participants with an Adverse Event leading to discontinuation (AEsDC) due to any cause. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment.
Percentage of Participants Who Experienced Death	Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months)	Percentage of Participants who experienced Death due to any cause
Progression Free Survival Rate (PFSR) at 24 Months	At 24 Months	The proportion of participants remaining progression free and surviving at 6 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on 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. Note: the appearance of one or more new lesions is also considered progression.
Progression Free Survival Rate (PFSR) by Tumor Histology at 12 Months	At 12 Months	The proportion of participants remaining progression free and surviving at 6 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on 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. Note: the appearance of one or more new lesions is also considered progression.
Percentage of Participants With an Immune Mediated Adverse Events (IMAEs)	Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months)	Percentage of Participants with an Immune Mediated Adverse Events treated with Immune-Modulating Medication
Percentage of Participants With an Event of Special Interest (ESI)	Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months)	Other ESI included the following categories: demyelination, encephalitis, Guillain-Barré syndrome (GBS), myasthenic syndrome, pancreatitis, uveitis, myositis, myocarditis, rhabdomyolysis, and Graft Versus Host Disease (GVHD).
Percentage of Participants With an Serious Adverse Events (SAEs)	Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months)	Percentage of participants with an Serious Adverse Event due to any cause. A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: 1. results in death 2. 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) 3. requires inpatient hospitalization or causes prolongation of existing hospitalization 4. results in persistent or significant disability/incapacity 5. is a congenital anomaly/birth defect 6. is an important medical event (defined as a medical event(s) that may not be immediately life-threatening or result in death or hospitalization but, based upon appropriate medical and scientific judgment, may jeopardize the participant or may require intervention \[eg, medical, surgical\] to prevent one of the other serious outcomes listed in the definition above.)
Progression Free Survival Rate (PFSR) by Response Criteria at 12 Months	At 12 Months	The proportion of participants remaining progression free and surviving at 12 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum 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. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage from the baseline study to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Overall Survival Rate by Histology at 12 Months	at 12 Months	The proportion of participants alive at 12 months. OS is defined as time from the date of randomization to the date of death. Participants who did not die by the end of the study will be censored at the last known date alive. OS rate by histology did not have data collected after 12 months randomization.
Percentage of Participants With an Select Adverse Events	Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months)	Percentage of Participants with an Select Adverse Event due to any cause Select adverse events include adverse events in the following systems: Gastrointestinal, Hepatic, Pulmonary, Renal, Skin, Hypersensitivity/Infusion reaction and Endocrine.
Number of Participants With Laboratory Test Abnormalities	Between first dose and 100 days after last dose of study therapy (Approximately Up to 16 months)	Number of participants with any laboratory test result that is clinically significant or meets the definition of an SAE (Grade 3+4 combined)

Trial Locations

Locations (116): Local Institution - 0004
🇺🇸
Birmingham, Alabama, United States
Local Institution - 0030
🇺🇸
Phoenix, Arizona, United States
Local Institution - 0041
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Phoenix, Arizona, United States
CBCC Global Research, Inc.
🇺🇸
Bakersfield, California, United States
Southern California Permanente Medical Group
🇺🇸
Bellflower, California, United States
St Jude Hospital Yorba Linda
🇺🇸
Fullerton, California, United States
Local Institution - 0046
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Los Angeles, California, United States
Local Institution - 0126
🇺🇸
Orange, California, United States
Torrance Health Association
🇺🇸
Redondo Beach, California, United States
Sharp Memorial Hospital
🇺🇸
San Diego, California, United States
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Local Institution - 0004
🇺🇸Birmingham, Alabama, United States