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NEPTUNE: Phase III study of first-line durvalumab plus tremelimumab in patients with metastatic NSCLC
de Castro, G., Jr. Rizvi, N. A. Schmid, P. Syrigos, K. Martin, C. Yamamoto, N. Cheng, Y. Moiseyenko, V. Summers, Yvonne J Vynnychenko, I.
de Castro, G., Jr.
Rizvi, N. A.
Schmid, P.
Syrigos, K.
Martin, C.
Yamamoto, N.
Cheng, Y.
Moiseyenko, V.
Summers, Yvonne J
Vynnychenko, I.
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Abstract
Introduction: 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.
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Date
2022
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Citation
de 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.