A Phase III Randomized Study of Nivolumab Plus Ipilimumab Versus Nivolumab for Previously Treated Patients With Stage IV Squamous Cell Lung Cancer and No Matching Biomarker (Lung-Map Sub-Study)
Overview
- Phase
- Phase 3
- Intervention
- Quality-of-Life Assessment
- Conditions
- Recurrent Squamous Cell Lung Carcinoma
- Sponsor
- SWOG Cancer Research Network
- Enrollment
- 275
- Locations
- 1202
- Primary Endpoint
- Overall Survival
- Status
- Active, not recruiting
- Last Updated
- 11 months ago
Overview
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.
Investigators
Eligibility Criteria
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
Exclusion Criteria
- Not provided
Arms & Interventions
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.
Intervention: Quality-of-Life Assessment
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.
Intervention: Ipilimumab
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.
Intervention: Laboratory Biomarker Analysis
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.
Intervention: Nivolumab
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.
Intervention: Quality-of-Life Assessment
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.
Intervention: Questionnaire Administration
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.
Intervention: Laboratory Biomarker Analysis
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.
Intervention: Nivolumab
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.
Intervention: Questionnaire Administration
Outcomes
Primary Outcomes
Overall Survival
Time Frame: From date of registration to maximum of 3 years or death
Duration from randomization to death due to any cause
Secondary Outcomes
- Investigator-assessed Progression-free Survival (IA-PFS)(From date of registration to maximum of 3 years or death)
- Objective Response Rate(From date of registration to maximum of 3 years or death)
- 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)