Abstract CT070: A open-label phase 3b/4 safety trial of flat-dose nivolumab in combination with ipilimumab in patients with advanced non-small cell lung cancer (NSCLC)
Authors: Pillai Rathi N. , Lash Bradley , Albert Istvan , Gagnon Gabrielle , Chakmakjian Carl , Ready Neal , Hu Wenhua , Krug Lee , Mukhopadhyay Sutapa , Paz-Ares Luis 
Published: July 2017

Abstract
Background: Nivolumab and ipilimumab are immune checkpoint inhibitor antibodies with distinct but complementary mechanisms of action, and their combination may improve clinical outcomes compared with single-agent therapy. Nivolumab plus ipilimumab is approved for the first-line treatment of metastatic melanoma and has shown encouraging clinical activity in other tumor types, including NSCLC. In CheckMate 012, a multi-cohort phase 1 trial that evaluated nivolumab as monotherapy or in combination with other agents in chemotherapy-naïve patients with NSCLC, weight-based administration of nivolumab (3 mg/kg) plus ipilimumab (1 mg/kg) yielded objective response rates (ORR) of up to 47%, depending on the dosing schedule. The discontinuation rates attributable to treatment-related adverse events (AEs) in patients treated with nivolumab plus ipilimumab were similar to nivolumab monotherapy, and AEs were consistent with the known safety profiles of the individual agents. Pharmacokinetic, safety, and efficacy data indicate comparable safety and efficacy profiles for 240 mg flat-dose nivolumab and 3 mg/kg nivolumab. This open-label phase 3b/4 study (ClinicalTrials.gov identifier: NCT02869789) will characterize the safety of flat-dose nivolumab combined with ipilimumab in patients with advanced NSCLC. Moreover, this study will evaluate this combination in special patient populations that are typically excluded from NSCLC trials.
Methods: Adult patients with stage IV/recurrent NSCLC and no prior systemic anticancer therapy, including epidermal growth factor receptor and anaplastic lymphoma kinase inhibitors (cohort A), or with stage IIIb/IV NSCLC and recurrence or progression during or after one prior platinum doublet chemotherapy regimen (cohort B) will be enrolled, with a planned sample size of 400 patients per cohort. Patients are required to have assessment of programmed death-1 ligand 1 expression, Eastern Cooperative Oncology Group performance status (ECOG PS) 0–1, and no untreated brain metastases, carcinomatous meningitis, autoimmune disease, or active malignancy requiring concurrent intervention. A third cohort (A1) of approximately 200 patients with no prior systemic therapy will have either ECOG PS 2 or one or more of the following: asymptomatic untreated brain metastases, renal or hepatic dysfunction, and/or HIV. All patients will receive flat-dose nivolumab (240 mg every 2 weeks) combined with weight-based ipilimumab (1 mg/kg every 6 weeks). The primary endpoint is a descriptive assessment of the number and percentage of patients with high-grade treatment-related select and immune-mediated AEs in cohorts A and B. Secondary efficacy endpoints include progression-free survival, ORR, duration of response, and patient-reported outcomes based on the Functional Assessment of Cancer Therapy-Lung (FACT-L).
Citation Format: Rathi N. Pillai, Bradley Lash, Istvan Albert, Gabrielle Gagnon, Carl Chakmakjian, Neal Ready, Wenhua Hu, Lee Krug, Sutapa Mukhopadhyay, Luis Paz-Ares. A open-label phase 3b/4 safety trial of flat-dose nivolumab in combination with ipilimumab in patients with advanced non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT070. doi:10.1158/1538-7445.AM2017-CT070