First-Line Durvalumab plus Tremelimumab vs Platinum-Based Chemotherapy for Advanced/Metastatic NSCLC: Phase 3 NEPTUNE Study
Invited conference paper presented and published in conference proceedings


摘要Background: Current first-line therapy for advanced EGFR and ALK wild-type NSCLC is associated with poor
survival and there remains a significant need for more effective treatments in this population. Blockade of immune
checkpoints programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4)
represents a promising anticancer therapeutic strategy.
In preclinical models, targeting both PD-1 and CTLA-4 provides for non-redundant pathway blockade and potential
synergy. Durvalumab (MEDI4736) is a selective, high-affinity, engineered human IgG1 mAb that blocks
programmed cell death ligand-1 (PD-L1) binding to PD-1 (IC50 0.1 nM) and CD80 (IC50 0.04 nM). Tremelimumab
is a selective human IgG2 mAb inhibitor of CTLA-4. A Phase 1b study of durvalumab + tremelimumab
demonstrated encouraging clinical activity and a manageable tolerability profile in advanced NSCLC, with
activity observed in patients with high and low/no tumor PD-L1 expression (NCT02000947).

Methods: NEPTUNE (NCT02542293) is a randomised, open-label, multicentre, global, Phase 3 study. Immunotherapy- and chemotherapy-naïve patients with advanced/metastatic EGFR and ALK wild-type NSCLC
(with either PD-L1 high expression [25% tumor cells staining for PD-L1 at any intensity] or PD-L1 low/
negative expression [<25% tumor cells staining for PDL1 at any intensity] ) will be randomised (1:1) to durvalumab
(20 mg/kg i.v. every 4 weeks [q4w] for up to 12 months) + tremelimumab (1 mg/kg i.v. q4w for up to 4
doses); or standard-of-care platinum-based doublet chemotherapy. The primary endpoint is overall survival
(OS). Secondary endpoints are progression-free survival (PFS), objective response rate (ORR), duration of
response and proportion of patients alive and progression free at 12 months by investigator assessment
(RECIST v1.1); time from randomisation to second progression; OS, PFS and ORR in patients with PD-L1 low/
negative NSCLC; safety (CTCAE v4.03) and tolerability; pharmacokinetics; and immunogenicity. Exploratory
outcomes include potential biomarkers of response to treatment and impact of subsequent anticancer therapies
on OS. Recruitment is ongoing.

Results: Not-applicable.

Conclusion: Not-applicable
著者Tony Mok, Peter Schmid, Gilberto De Castro Jr, Kostas Syrigos, Claudio Martin, Nobuyuki Yamamoto, Osvaldo Arén,
Oscar Arrieta, Maya Gottfried, Abdul Rahman Jazieh, Rodryg Ramlau, Constanta Timcheva, Leonardo Trani
會議名稱IASLC 17th World Conference on Lung Cancer Dec 4-7, 2016
會議論文集題名Journal of Thoracic Oncology
期次1 Supplement
頁次S1084 - S1084

上次更新時間 2020-22-09 於 03:28