The investigators propose a trial to evaluate if the addition of ipilimumab to nivolumab after primary resistance to anti- programmed death 1 (PD-1) axis therapy can lead to objective radiographic tumor regression.
Name: combination nivolumab and ipilimumab
Description: Combination therapy with nivolumab 3 mg/kg administered intravenously (IV) every 2 weeks, with ipilimumab 1 mg/kg administered IV every 6 weeks.Type: Biologicalcombination nivolumab and ipilimumab
Description: Objective response is defined as a complete or partial response, as determined by investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 confirmed by repeat assessment ≥4 weeks after initial documentation.
Measure: Objective response rate using RECIST v1.1 to nivolumab and ipilimumab when administered in combination to patients with pre-treated advanced NSCLC who have experienced primary resistance to anti-PD-1 axis therapy as their last line of systemic therapy. Time: Tumor response assessment will occur every 8 weeks after initiating trial therapy for the first 24 weeks, and thereafter every 12 weeks up to 4 years.Description: Progression free survival is defined as the time from the first day of nivolumab treatment until progression of disease using RECIST v1.1 and immune related Response Criteria (irRC)
Measure: Progression-free survival with nivolumab and ipilimumab when administered in combination to patients with pre- treated advanced NSCLC who have experienced primary resistance to anti-PD-1 axis therapy as their last line of systemic therapy Time: Until disease progression, unacceptable toxicity, or study termination, up to four years.Description: Overall survival is defined as the time from the first day of treatment until death from any cause. If a patient has not experienced death, OS will be censored at the day of last follow-up.
Measure: Overall survival (OS) with nivolumab and ipilimumab when administered in combination to patients with pre- treated advanced NSCLC who have experienced PRIMARY resistance to anti-PD-1 axis therapy as their last line of systemic therapy. Time: Until death or day of last follow-up, up to four years from enrollment.Description: Objective response is defined as a complete or partial response, as determined by investigator assessment using irRC and confirmed by repeat assessment ≥4 weeks after initial documentation.
Measure: Objective response rate using irRC to nivolumab and ipilimumab when administered in combination to patients with pre-treated advanced NSCLC who have experienced primary resistance to anti-PD-1 axis therapy as their last line of systemic therapy. Time: Tumor response assessment will occur every 9 weeks after initiating trial therapy for the first 24 weeks, and thereafter every 12 weeks, up to four years.Description: Objective response is defined as a complete or partial response, as determined by investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and immune-related Response Criteria and confirmed by repeat assessment ≥4 weeks after initial documentation.
Measure: Objective response rate in in advanced non-small cell lung cancer (NSCLC) with ACQUIRED resistance to anti-programmed death (PD)-1 axis therapy as their last line of systemic therapy. Time: Tumor response assessment will occur every 9 weeks after initiating trial therapy for the first 24 weeks, and thereafter every 12 weeks, up to four years.Description: Progression free survival is defined as the time from the first day of nivolumab treatment until progression of disease using RECIST v1.1 and immune related Response Criteria
Measure: Progression free survival by RECIST v1.1 with nivolumab and ipilimumab in patients with pre-treated advanced NSCLC who have experienced acquired resistance to anti-PD-1 axis therapy as their last line of systemic therapy. Time: Until disease progression, unacceptable toxicity, or study termination, up to four years from enrollment.Description: Overall survival is defined as the time from the first day of treatment until death from any cause. If a patient has not experienced death, OS will be censored at the day of last follow-up.
Measure: Overall survival with nivolumab and ipilimumab in patients with pre-treated advanced NSCLC who have experienced ACQUIRED resistance to anti-PD-1 axis therapy as their last line of systemic therapy. Time: Until death or day of last follow-up (up to four years from study enrollment).Description: Determined based on adverse events which will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0.
Measure: Safety of nivolumab and ipilimumab when administered in combination in patients with pre-treated advanced NSCLC who have experienced PRIMARY or ACQUIRED resistance to anti-PD-1 axis therapy as their last line of systemic therapy. Time: From date of first treatment until 100 days from discontinuation of treatment.Single Group Assignment
There is one SNP
1. Patients with TKI-treated EGFR mutant NSCLC harboring the secondary EGFR T790M tumor must have received prior osimertinib 2. Patients with crizotinib-treated ALK rearranged NSCLC must have received a next generation ALK inhibitor (e.g. --- T790M ---