30th Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2015)
An open label randomized Phase III trial of nivolumab or nivolumab plus ipilimumab vs platinum doublet chemotherapy (PT-DC) in patients with chemotherapy-naïve stage IV or recurrent non-small cell lung cancer (NSCLC) (CheckMate 227)
Journal for ImmunoTherapy of Cancer volume 3, Article number: P154 (2015)
Patients with advanced NSCLC are treated with first-line PT-DC, which is associated with a median OS of 8–10 months and 1-year and 2-year survival rates of 30–40% and 10–15%, respectively. Nivolumab (a fully human IgG4 anti-programmed death-1 immune checkpoint inhibitor antibody) alone and in combination with ipilimumab (a fully human IgG4 cytotoxic T-lymphocyte antigen-4 immune checkpoint inhibitor antibody) has demonstrated encouraging clinical benefit across multiple tumor types. Two randomized Phase III trials demonstrated superior survival with nivolumab vs docetaxel in previously-treated patients with advanced squamous (SQ) (CheckMate 017) and non-squamous (non-SQ) NSCLC (CheckMate 057). Preliminary results of a Phase I study (CheckMate 012) of nivolumab with or without ipilimumab demonstrate acceptable safety and encouraging activity in first-line metastatic NSCLC across histologies. This Phase III trial (CheckMate 227) evaluates nivolumab monotherapy and nivolumab plus ipilimumab combination regimens vs PT-DC in patients with chemotherapy-naïve stage IV or recurrent SQ and non-SQ NSCLC.
Adult patients with stage IV or recurrent NSCLC, ECOG performance status ≤1, no prior systemic anti-cancer therapy, and measureable disease per RECIST version 1.1 are eligible. Tissue will be evaluated for programmed death-ligand 1 (PD-L1) expression during screening. Patients who have untreated CNS metastases are ineligible. Patients will be randomized to nivolumab monotherapy, nivolumab plus ipilimumab combination regimens, or PT-DC. PT-DC will be administered according to histology (gemcitabine with cisplatin or carboplatin for SQ and pemetrexed with cisplatin or carboplatin for non-SQ). Patients will receive treatment until progression or unacceptable toxicity. The co-primary endpoints are overall survival and progression-free survival in patients receiving nivolumab monotherapy or nivolumab plus ipilimumab combination regimens vs patients receiving PT-DC. Secondary endpoints include objective response rate in nivolumab monotherapy or nivolumab plus ipilimumab combination regimens vs PT-DC and disease related symptom improvement measured by the Lung Cancer Symptom Scale in all patients.
ClinicalTrials.gov identifier NCT02477826.
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Hellmann, M., Ramalingam, S., Reck, M. et al. An open label randomized Phase III trial of nivolumab or nivolumab plus ipilimumab vs platinum doublet chemotherapy (PT-DC) in patients with chemotherapy-naïve stage IV or recurrent non-small cell lung cancer (NSCLC) (CheckMate 227). j. immunotherapy cancer 3 (Suppl 2), P154 (2015). https://doi.org/10.1186/2051-1426-3-S2-P154