CheckMate 384: A phase 3b/4 dose-frequency optimization trial of nivolumab in advanced or metastatic non-small cell lung cancer

Abstract

Background: Nivolumab, an anti-programmed death-1 antibody, is approved for previously treated metastatic NSCLC, advanced melanoma, advanced renal cell carcinoma (RCC), and relapsed/progressive classical Hodgkin lymphoma. In two phase 3 trials (CheckMate 017 and 057), nivolumab 3 mg/kg every 2 weeks (Q2W) demonstrated superior survival and favorable safety versus docetaxel in previously treated patients with metastatic NSCLC. Clinically meaningful efficacy and a manageable safety profile have been observed in studies in melanoma (CheckMate 037, 066, and 067), RCC (CheckMate 025), and Hodgkin lymphoma (CheckMate 205 and 039). On this basis, the currently approved nivolumab dose is 3 mg/kg Q2W. Decreasing the frequency of nivolumab administration may enhance convenience and compliance while maintaining efficacy and safety in patients who receive long-term nivolumab therapy. CheckMate 384 is a phase 3B/4 trial that will evaluate the efficacy and safety of nivolumab administered at two dosing frequencies in patients with advanced/metastatic NSCLC following w4 months' administration of nivolumab 3 mg/kg or 240 mg Q2W. Methods: Adult patients with advanced/metastatic squamous or nonsquamous NSCLC and ECOG performance status 0-2 are eligible; disease can be newly diagnosed or recurrent/progressive following multimodal therapy. Patients with untreated, symptomatic brain metastases are ineligible. Patients must have tolerated and completed ∼4 months (16 ± 2 weeks) of treatment with nivolumab (3 mg/kg or 240 mg) IV Q2W and achieved a complete or partial response or stable disease. After this pre-study period, patients will be randomized 1:1 to receive IV nivolumab on one of two fixed-dose regimens: 240 mg Q2W or 480 mg Q4W. Randomization will be stratified by histology and response to pre-study nivolumab treatment at randomization (complete/partial response vs stable disease). The table shows primary/secondary endpoints; the objective is to establish that nivolumab 480 mg Q4W is not inferior to 240 mg Q2W. Planned enrollment is 620 patients. (Table Presented).