140TiP - CheckMate 384: A phase 3b/4 dose-frequency optimization trial of nivolumab in advanced or metastatic non-small cell lung cancer

Date 07 May 2017
Event ELCC 2017
Session Poster Display Session
Topics Immunotherapy
Thoracic Malignancies
Non-Small Cell Lung Cancer
Presenter Neils Reinmuth
Citation Annals of Oncology (2017) 28 (suppl_2): ii28-ii51. 10.1093/annonc/mdx091
Authors N. Reinmuth1, R. Harris2, P. Mitchell3, E.B. Garon4, J. Zhu5, I. Chang5, G. Selvaggi5, E. Pichon6
  • 1Asklepios Clinic Gauting, 22359 - Gauting/DE
  • 2Broome Oncology and US Oncology Research, 13790 - Johnson City/US
  • 3Austin Health, Melbourne/AU
  • 4UCLA/TRIO, Santa Monica/US
  • 5Bristol-Myers Squibb, Princeton/US
  • 6CHU Tours-Bretonneau, 37000 - Tours/FR



Nivolumab, an anti-programmed death-1 antibody, is approved for the treatment of various cancers. Based on efficacy and safety findings across multiple tumor types, the approved dose of nivolumab was, until recently, 3 mg/kg every 2 weeks (Q2W). In September 2016, the approved nivolumab dose in non-small cell lung cancer (NSCLC), melanoma, and renal cell carcinoma was modified in the United States to a flat dose of 240 mg Q2W. Reducing the frequency of nivolumab administration may increase convenience and compliance while maintaining efficacy and safety in patients receiving long-term nivolumab therapy. CheckMate 384, a randomized, open-label phase 3b/4 trial (NCT02713867) was designed to evaluate less frequent nivolumab dosing (480 mg every 4 weeks [Q4W] vs 240 mg Q2W) in patients with advanced/metastatic NSCLC following up to 12 months of prior treatment with nivolumab 3 mg/kg or 240 mg Q2W.

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 intravenous nivolumab 3 mg/kg or 240 mg Q2W for up to 12 months and achieved a complete or partial response or stable disease confirmed on 2 consecutive assessments. Patients with untreated, symptomatic central nervous system metastases are not eligible. Patients are randomized 1:1 to receive intravenous nivolumab in 1 of 2 flat-dose schedules: 240 mg Q2W or 480 mg Q4W. Randomization is stratified by histology and response to pre-study nivolumab treatment (complete/partial response vs stable disease). Endpoints are shown in the table. The primary objective is to compare 6-month and 1-year progression-free survival (PFS) rates between patients who received nivolumab 480 mg Q4W and those who received 240 mg Q2W. Planned enrollment is 620 patients.rnTable: 140TiP

Study endpoints

rnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrn rnrn
PFS 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 randomization
PFS rate at 2 years after randomization
Overall survival rate
Safety and tolerability, as assessed by incidence and severity of adverse events

Clinical trial identification


Legal entity responsible for the study

Bristol-Myers Squibb


Bristol-Myers Squibb


N. Reinmuth: Personal fees (speakers and consulting honoraria): Bristol-Myers Squibb, Hoffmann-La Roche, Lilly, Novartis, Boehringer-Ingelheim, AstraZeneca, Amgen, Pfizer, MSD. R. Harris: Consultant (personal fees): Bristol-Myers Squibb. P. Mitchell: Advisory board member: AstraZeneca, Roche, Boehringer-Ingelheim, BMS, MSD, Celgene; Honoraria: Roche; Travel grants: Roche, BMS. E.B. Garon: Research Funding (received by my institution): AstraZeneca, BMS, Merck, Genentech, Eli Lilly, Pfizer, Novartis, Boehringer Ingelheim, Mirati. J. Zhu, I-F. Chang: BMS Employment and BMS Stock Ownership. S. Selvaggi: Bristol-Myers Squibb employee and shareholder and has received travel, accommodation, and expense assistance from Bristol-Myers Squibb. All other authors have declared no conflicts of interest.