Recurrent Squamous Cell Lung Carcinoma, Stage IV Squamous Cell Lung Carcinoma AJCC v7
Conditions
Brief summary
This randomized phase III trial compares nivolumab with ipilimumab and nivolumab alone in treating patients with stage IV squamous cell lung cancer that has come back after previous treatment. This is a "non-match" sub-study that includes all screened patients not eligible for a biomarker-driven sub-study. Monoclonal antibodies, such as nivolumab and ipilimumab, may be able to shrink tumors. It is not yet known whether nivolumab works better with or without ipilimumab in treating patients with squamous cell lung cancer.
Detailed description
PRIMARY OBJECTIVES: I. To compare overall survival (OS) in patients with advanced stage refractory squamous cell carcinoma (SCCA) of the lung randomized to nivolumab plus ipilimumab versus nivolumab. SECONDARY OBJECTIVES: I. To compare investigator-assessed progression-free survival (IA-PFS) in patients with advanced stage refractory SCCA of the lung randomized to nivolumab plus ipilimumab versus nivolumab. II. To compare the response rates (confirmed and unconfirmed, complete and partial) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 among patients randomized to receive nivolumab plus ipilimumab versus nivolumab. III. To compare the response rates (confirmed only, complete and partial) per RECIST 1.1 among patients randomized to receive nivolumab plus ipilimumab versus nivolumab. IV. To evaluate the frequency and severity of toxicities associated with nivolumab plus ipilimumab versus nivolumab. TRANSLATIONAL MEDICINE OBJECTIVES: I. To evaluate if there is a differential treatment effect on OS, IA-PFS, and response by tumor programmed death-ligand 1 (PD-L1) expression status. II. To examine patient reported outcomes by treatment arm. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1 and ipilimumab IV over 60 minutes on day 1 of every third course (every 42 days). Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive nivolumab IV over 30 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment but prior to disease progression, patients are followed up every 3 months for 1 year and then every 6 months for up to 3 years. After disease progression, patients are followed up every 6 months for 2 years and at end of year 3 after sub-study registration.
Interventions
BIOLOGICALIpilimumab
Given IV
OTHERLaboratory Biomarker Analysis
Correlative studies
BIOLOGICALNivolumab
Given IV
OTHERQuality-of-Life Assessment
Ancillary studies
OTHERQuestionnaire Administration
Ancillary studies
Sponsors
SWOG Cancer Research Network
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must meet all SCREENING/PRE-SCREENING and SUB-STUDY REGISTRATION COMMON ELIGIBILITY CRITERIA as specified in S1400: Phase II/III Biomarker-Driven Master Protocol for Previously Treated Squamous Cell Lung Cancer (Lung-Map) * Patients must have been assigned to S1400I * Patients must not have had prior treatment with an anti-programmed cell death (PD)-1, anti-PD-L1, anti-PD-L2, anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways * Patients must not have an active, known, or suspected autoimmune disease; patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger * Patients must not have any known allergy or reaction to any component of the nivolumab and ipilimumab formulations * Patients must not have received systemic treatment with corticosteroids (\> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days prior to sub-study registration; inhaled or topical steroids, and adrenal replacement doses =\< 10 mg daily prednisone or equivalent are permitted in the absence of active autoimmune disease * Patients must not have a known positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection; patients with a positive hepatitis C antibody with a negative viral load are allowed * Patients must not have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) * Patients must not have interstitial lung disease that is symptomatic or disease that may interfere with the detection or management of suspected drug-related pulmonary toxicity * Patients must also be offered participation in banking for future use of specimens * Patients must have a lipase, amylase, TSH with reflex free T3/T4 performed within 7 days prior to sub-study registration * Patients must not have any grade III/IV cardiac disease as defined by the New York Heart Association Criteria (i.e., patients with cardiac disease resulting in marked limitation of physical activity or resulting in inability to carry on any physical activity without discomfort), unstable angina pectoris, and myocardial infarction within 6 months, or serious uncontrolled cardiac arrhythmia * Patients with a history of congestive heart failure (CHF) or at risk because of underlying cardiovascular disease or exposure to cardiotoxic drug should have an electrocardiogram (EKG) and echocardiogram performed to evaluate cardiac function as clinically indicated * Patients with evidence of congestive heart failure (CHF), myocardial infarction (MI), cardiomyopathy, or myositis should have a cardiac evaluation including lab tests and cardiology consultations as clinically indicated including EKG, creatine phosphokinase (CPK), troponin, and echocardiogram * Patients who can complete Patient Reported Outcomes (PRO) forms in English are required to complete a pre-study S1400I Patient Reported Outcomes (PRO) Questionnaire and a pre-study S1400I European Quality of Life Five Dimension (EQ-5D) Questionnaire within 14 days prior to registration; NOTE: Patients enrolled to S1400I prior to 9/1/2016 are not eligible for the PRO study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | From date of registration to maximum of 3 years or death | Duration from randomization to death due to any cause |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Investigator-assessed Progression-free Survival (IA-PFS) | From date of registration to maximum of 3 years or death | Duration from randomization to first occurrence of progression by RECIST 1.1, symptomatic deterioration, or death due to any cause. The IA-PFS for patients last known to be alive and free of progression or symptomatic deterioration was censored at the date of last disease assessment. Progression is defined as one or more of the following: 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline as well as an absolute increase of at least 0.5 cm; Unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided); Appearance of any new lesion/site; Death due to disease without prior documentation of progression and without symptomatic deterioration |
| Objective Response Rate | From date of registration to maximum of 3 years or death | Response was defined as the occurrence of a complete or partial response, confirmed or unconfirmed per RECIST 1.1 criteria. Response for patients not known to have a response was coded as nonresponse. Complete response: Complete disappearance of all target and non-target lesions. No new lesions. No disease related symptoms. Any lymph nodes (whether target or non-target) must have reduction in short axis to \< 1.0 cm. All disease must be assessed using the same technique as baseline. Partial response: Applies only to patients with at least one measurable lesion. Greater than or equal to 30% decrease under baseline of the sum of appropriate diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions. All target measurable lesions must be assessed using the same techniques as baseline. |
| Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Duration of treatment and follow up until death or 3 years post registration | Only adverse events that are possibly, probably or definitely related to study drug are reported. CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for reporting SAEs. |
Countries
Canada, United States
Contacts
PRINCIPAL_INVESTIGATORVassiliki Papadimitrakopoulou
SWOG Cancer Research Network
Participant flow
Pre-assignment details
Of 275 enrolled patients, 252 were deemed eligible (125 randomized to nivolumab/ipilimumab and 127 to nivolumab).
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Nivolumab, Ipilimumab) Patients receive nivolumab IV over 30 minutes on day 1 and ipilimumab IV over 60 minutes on day 1 of every third course (every 42 days). Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Ipilimumab: Given IV
Laboratory Biomarker Analysis: Correlative studies
Nivolumab: Given IV
Quality-of-Life Assessment: Ancillary studies
Questionnaire Administration: Ancillary studies | 125 |
| Arm II (Nivolumab) Patients receive nivolumab IV over 30 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Laboratory Biomarker Analysis: Correlative studies
Nivolumab: Given IV
Quality-of-Life Assessment: Ancillary studies
Questionnaire Administration: Ancillary studies | 127 |
| Total | 252 |
Baseline characteristics
| Characteristic | Arm II (Nivolumab) | Arm I (Nivolumab, Ipilimumab) | Total |
|---|---|---|---|
| Age, Continuous | 68.1 years | 67.5 years | 67.5 years |
| Brain metastases at baseline | 12 Participants | 8 Participants | 20 Participants |
| Liver metastases at baseline | 30 Participants | 23 Participants | 53 Participants |
| No. of prior systemic therapies for stage IV or recurrent disease 0 | 35 Participants | 35 Participants | 70 Participants |
| No. of prior systemic therapies for stage IV or recurrent disease 1 | 77 Participants | 73 Participants | 150 Participants |
| No. of prior systemic therapies for stage IV or recurrent disease 2 | 7 Participants | 6 Participants | 13 Participants |
| No. of prior systemic therapies for stage IV or recurrent disease ≥3 | 1 Participants | 3 Participants | 4 Participants |
| No. of prior systemic therapies for stage IV or recurrent disease Unknown | 7 Participants | 8 Participants | 15 Participants |
| Prior radiation therapy Localized radiation | 49 participants | 36 participants | 85 participants |
| Prior radiation therapy Radiation with curative intent | 45 participants | 41 participants | 86 participants |
| Race/Ethnicity, Customized Asian | 4 participants | 0 participants | 4 participants |
| Race/Ethnicity, Customized Black | 16 participants | 17 participants | 33 participants |
| Race/Ethnicity, Customized Hispanic ethnicity | 1 participants | 2 participants | 3 participants |
| Race/Ethnicity, Customized Multiracial | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Native American | 2 participants | 1 participants | 3 participants |
| Race/Ethnicity, Customized Pacific Islander | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Unknown ethnicity | 0 participants | 3 participants | 3 participants |
| Race/Ethnicity, Customized Unknown race | 0 participants | 4 participants | 4 participants |
| Race/Ethnicity, Customized White | 104 participants | 102 participants | 206 participants |
| Sex: Female, Male Female | 41 Participants | 42 Participants | 83 Participants |
| Sex: Female, Male Male | 86 Participants | 83 Participants | 169 Participants |
| Smoking status Current | 54 Participants | 48 Participants | 102 Participants |
| Smoking status Former | 72 Participants | 75 Participants | 147 Participants |
| Smoking status Never | 1 Participants | 2 Participants | 3 Participants |
| Weight loss in past 6 months 10% to <20% | 13 Participants | 13 Participants | 26 Participants |
| Weight loss in past 6 months ≥20% | 3 Participants | 1 Participants | 4 Participants |
| Weight loss in past 6 months <5% | 93 Participants | 86 Participants | 179 Participants |
| Weight loss in past 6 months 5% to <10% | 18 Participants | 25 Participants | 43 Participants |
| Zubrod performance score 0 | 35 Participants | 36 Participants | 71 Participants |
| Zubrod performance score 1 | 92 Participants | 89 Participants | 181 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 92 / 125 | 105 / 127 |
| other Total, other adverse events | 122 / 124 | 123 / 123 |
| serious Total, serious adverse events | 78 / 124 | 58 / 123 |
Outcome results
Primary
Overall Survival
Duration from randomization to death due to any cause
Time frame: From date of registration to maximum of 3 years or death
Population: Eligible and evaluable participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Nivolumab, Ipilimumab) | Overall Survival | 10 months |
| Arm II (Nivolumab) | Overall Survival | 11 months |
Secondary
Investigator-assessed Progression-free Survival (IA-PFS)
Duration from randomization to first occurrence of progression by RECIST 1.1, symptomatic deterioration, or death due to any cause. The IA-PFS for patients last known to be alive and free of progression or symptomatic deterioration was censored at the date of last disease assessment. Progression is defined as one or more of the following: 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline as well as an absolute increase of at least 0.5 cm; Unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided); Appearance of any new lesion/site; Death due to disease without prior documentation of progression and without symptomatic deterioration
Time frame: From date of registration to maximum of 3 years or death
Population: Eligible and evaluable participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Nivolumab, Ipilimumab) | Investigator-assessed Progression-free Survival (IA-PFS) | 3.8 months |
| Arm II (Nivolumab) | Investigator-assessed Progression-free Survival (IA-PFS) | 2.9 months |
Secondary
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs
Only adverse events that are possibly, probably or definitely related to study drug are reported. CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for reporting SAEs.
Time frame: Duration of treatment and follow up until death or 3 years post registration
Population: Participants who received at least one dose of protocol treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Abdominal pain | 1 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Acute kidney injury | 1 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Alanine aminotransferase increased | 5 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Alkaline phosphatase increased | 2 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anemia | 5 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anorexia | 2 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Blood bilirubin increased | 0 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Arthralgia | 2 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Aspartate aminotransferase increased | 6 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Atrioventricular block complete | 1 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Autoimmune disorder | 1 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Cardiac arrest | 1 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Cardiac troponin I increased | 1 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Chronic kidney disease | 0 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Colitis | 1 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Confusion | 2 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Constipation | 1 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Death NOS | 1 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dehydration | 2 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Diarrhea | 3 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dyspnea | 5 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Enterocolitis | 1 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Erythroderma | 1 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fall | 1 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fatigue | 11 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | General disorders and admin site conditions - Other | 1 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Generalized muscle weakness | 3 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Headache | 0 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Heart failure | 1 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hepatic failure | 1 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hepatobiliary disorders - Other, specify | 1 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypercalcemia | 2 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyperglycemia | 1 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyperkalemia | 1 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypertension | 4 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyperthyroidism | 1 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypoalbuminemia | 2 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypokalemia | 3 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyponatremia | 7 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypotension | 2 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypoxia | 4 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Infections and infestations - Other, specify | 0 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Insomnia | 1 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Leukocytosis | 1 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lipase increased | 6 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lung infection | 2 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lymphocyte count decreased | 3 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Memory impairment | 0 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Myalgia | 1 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Myocarditis | 1 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Myositis | 1 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Nausea | 0 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pancreatitis | 0 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Periorbital edema | 1 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pleural effusion | 1 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pneumonitis | 9 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Proteinuria | 0 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pruritus | 2 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Rash maculo-papular | 3 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Resp, thoracic and mediastinal disorders - Other | 2 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Respiratory failure | 2 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Sepsis | 1 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Serum amylase increased | 2 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Skin and subcutaneous tissue disorders - Other | 1 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Skin infection | 2 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Sore throat | 1 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Stroke | 1 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Supraventricular tachycardia | 1 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Syncope | 1 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Thromboembolic event | 1 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Treatment related secondary malignancy | 0 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Vomiting | 1 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Weight gain | 0 Participants |
| Arm I (Nivolumab, Ipilimumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Weight loss | 1 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pneumonitis | 6 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Abdominal pain | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypokalemia | 3 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Acute kidney injury | 1 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Thromboembolic event | 1 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Alanine aminotransferase increased | 2 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyponatremia | 3 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Alkaline phosphatase increased | 2 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Proteinuria | 1 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anemia | 1 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypotension | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Sore throat | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anorexia | 2 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypoxia | 1 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Arthralgia | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pruritus | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Aspartate aminotransferase increased | 2 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Infections and infestations - Other, specify | 1 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Atrioventricular block complete | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Weight loss | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Autoimmune disorder | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Blood bilirubin increased | 2 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Insomnia | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Cardiac arrest | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Rash maculo-papular | 1 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Cardiac troponin I increased | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Leukocytosis | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Chronic kidney disease | 1 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Stroke | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Colitis | 3 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lipase increased | 1 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Confusion | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Resp, thoracic and mediastinal disorders - Other | 1 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Constipation | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lung infection | 6 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Death NOS | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Treatment related secondary malignancy | 1 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dehydration | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lymphocyte count decreased | 5 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Diarrhea | 2 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Respiratory failure | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dyspnea | 5 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Memory impairment | 1 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Enterocolitis | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Supraventricular tachycardia | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Erythroderma | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Myalgia | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fall | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Sepsis | 1 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fatigue | 7 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Myocarditis | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | General disorders and admin site conditions - Other | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Weight gain | 1 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Generalized muscle weakness | 1 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Myositis | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Headache | 1 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Serum amylase increased | 1 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Heart failure | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Nausea | 2 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hepatic failure | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Syncope | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hepatobiliary disorders - Other, specify | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pancreatitis | 1 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypercalcemia | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Skin and subcutaneous tissue disorders - Other | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyperglycemia | 1 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Periorbital edema | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyperkalemia | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Vomiting | 1 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypertension | 1 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pleural effusion | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyperthyroidism | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Skin infection | 0 Participants |
| Arm II (Nivolumab) | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypoalbuminemia | 0 Participants |
Secondary
Objective Response Rate
Response was defined as the occurrence of a complete or partial response, confirmed or unconfirmed per RECIST 1.1 criteria. Response for patients not known to have a response was coded as nonresponse. Complete response: Complete disappearance of all target and non-target lesions. No new lesions. No disease related symptoms. Any lymph nodes (whether target or non-target) must have reduction in short axis to \< 1.0 cm. All disease must be assessed using the same technique as baseline. Partial response: Applies only to patients with at least one measurable lesion. Greater than or equal to 30% decrease under baseline of the sum of appropriate diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions. All target measurable lesions must be assessed using the same techniques as baseline.
Time frame: From date of registration to maximum of 3 years or death
Population: Eligible and evaluable participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (Nivolumab, Ipilimumab) | Objective Response Rate | 18 percentage of participants |
| Arm II (Nivolumab) | Objective Response Rate | 17 percentage of participants |