NEPTUNE: Phase III study of first-line durvalumab plus tremelimumab in patients with metastatic NSCLC
Authorsde Castro, G., Jr.
Rizvi, N. A.
Summers, Yvonne J
Lee, S. Y.
AffiliationInstituto do Câncer do Estado de São Paulo, São Paulo, Brazil.
MetadataShow full item record
AbstractIntroduction: NEPTUNE, a phase III, open-label study, evaluated first-line durvalumab plus tremelimumab versus chemotherapy in metastatic NSCLC (mNSCLC). Methods: Eligible patients with EGFR/ALK wild-type mNSCLC were randomized (1:1) to first-line durvalumab (20 mg/kg q4w until progression) plus tremelimumab (1 mg/kg q4w for up to 4 doses) or standard chemotherapy. Randomization was stratified by tumor PD-L1 expression (≥25% vs <25%), histology, and smoking history. The amended primary endpoint was overall survival (OS) in patients with blood tumor mutational burden ≥20 mut/Mb (bTMB ≥20). Secondary endpoints included progression-free survival (PFS) in patients with bTMB ≥20 and safety and tolerability in all treated patients. Results: As of June 24, 2019, 823 patients were randomized (intention-to-treat [ITT]); 512 (62%) were bTMB-evaluable, with 129/512 (25%) having bTMB ≥20 (durvalumab plus tremelimumab [n=69]; chemotherapy [n=60]). Baseline characteristics were balanced in the ITT. Among patients with bTMB ≥20, OS improvement with durvalumab plus tremelimumab versus chemotherapy did not reach statistical significance (HR 0.71 [95% CI, 0.49‒1.05; p=0.081]; median OS, 11.7 vs 9.1 months); the HR for PFS was 0.77 (95% CI, 0.51‒1.15; median PFS, 4.2 vs 5.1 months). In the overall safety population, incidence of grade 3/4 treatment-related adverse events was 20.7% (durvalumab plus tremelimumab) and 33.6% (chemotherapy). Conclusions: NEPTUNE did not meet its primary endpoint of improved OS with durvalumab plus tremelimumab versus chemotherapy in patients with mNSCLC and bTMB ≥20. Despite the amended study design, with a resultant small primary analysis population, therapeutic activity was aligned with expectations based on mechanistic biology and previous studies.
Citationde Castro G, Jr., Rizvi NA, Schmid P, Syrigos K, Martin C, Yamamoto N, et al. NEPTUNE: Phase III Study of First-Line Durvalumab Plus Tremelimumab in Patients With Metastatic NSCLC. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 2022 Oct 11. PubMed PMID: 36240972. Epub 2022/10/15. eng.
JournalJournal of Thoracic Oncology
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