196Tip CheckMate 384: A Phase 3b/4 Dose-Frequency Optimization Trial of Nivolumab in Advanced or Metastatic NSCLC

Background: Nivolumab, an anti-programmed death-1 antibody, is approved for previously treated metastatic non-small cell lung cancer (NSCLC) and various other cancers. Based on efficacy and safety results, the approved dosing frequency is every 2 weeks (Q2W) until progression or discontinuation due to toxicity. CheckMate 153 evaluated nivolumab treatment (tx) duration and demonstrated improved outcomes with continuous tx; 1-year progression-free survival (PFS) rates were higher in patients who continued vs stopped tx after 1 year. As an alternative to stopping tx, reducing dosing frequency could optimize convenience during long-term nivolumab therapy while maintaining efficacy and safety; recent exposure-response modeling predicted the benefit–risk profile of nivolumab 480 mg every 4 weeks (Q4W) to be similar to 3 mg/kg Q2W. CheckMate 384, a randomized, open-label phase 3b/4 trial was designed to evaluate less frequent nivolumab dosing (480 mg Q4W vs 240 mg Q2W) in patients with advanced/metastatic NSCLC and prior nivolumab tx. Trial design: Eligible patients are adults with advanced/metastatic squamous or non-squamous NSCLC and Eastern Cooperative Oncology Group performance status 0–2 who received prior nivolumab 3 mg/kg Q2W or 240 mg Q4W for up to 12 months with a complete or partial response or stable disease confirmed by 2 consecutive assessments. Patients with untreated, symptomatic central nervous system metastases are not eligible. Patients are randomized 1:1 to receive intravenous nivolumab 240 mg Q2W or 480 mg Q4W. Randomization is stratified by histology and response to pre-study nivolumab tx (complete/partial response vs stable disease). Endpoints are shown in the Table. The primary objective is to compare 6-month and 1-year PFS rates between patients who received nivolumab 480 mg Q4W and those who received 240 mg Q2W. Planned enrollment is 620 patients.TableStudy endpointsPrimarySecondaryPFS rates at 6 months and 1 year after randomization (co-primary) PFS rate at 1 year after randomization by tumor histology and by response to pre-study nivolumab before randomizationPFS rate at 2 years after randomizationOverall survival rateSafety and tolerability, as assessed by incidence and severity of adverse events Open table in a new tab Clinical trial identification: NCT02713867; First posted: March 21, 2016 Legal entity responsible for the study: Bristol-Myers Squibb Funding: Bristol-Myers Squibb Disclosure: E. Garon: Research funding from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Genentech, Merck, Novartis, and Pfizer. N. Reinmuth: Speaker and consulting honoraria and fees from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Hoffmann-La Roche, Lilly, MSD, Novartis, and Pfizer. R. Harris: Consultant for Bristol-Myers Squibb. P. Mitchell: Advisory boards for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Merck Serono, and Roche; Received research funding from Merck Serono. Received honoraria and travel grants from Roche. J. Zhu, G. Selvaggi, S. Agrawal: Employee and shareholder of Bristol-Myers Squibb. All other authors have declared no conflicts of interest.