Phase II Dose-Randomized Study of Sunvozertinib in Platinum-Pretreated Non-Small Cell Lung Cancer With Epidermal Growth Factor Receptor Exon 20 Insertion Mutations (WU-KONG1B).
Journal
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Journal Volume
43
Journal Issue
29
Start Page
3198
End Page
3208
ISSN
1527-7755
Date Issued
2025-10-10
Author(s)
Wang, Mengzhao
Doucet, Ludovic
Lv, Dongqing
Sun, Meili
Huang, Dingzhi
Greillier, Laurent
Planchard, David
Hong, Qunying
Mazieres, Julien
Felip, Enriqueta
Li, Xingya
Hu, Ying
Fang, Jian
Bazhenova, Lyudmila
Ghiringhelli, François
Cobo Dols, Manuel Angel
Rodriguez, Luis Paz-Ares
Bearz, Alessandra
Pellini, Bruna
Kim, Yu Jung
Bosch-Barrera, Joaquim
Shim, Byoung-Yong
Luo, Yung-Hung
Tiseo, Marcello
Yang, Tsung-Ying
Carcereny, Enric
Memmott, Regan M
Zalcman, Gerard
de Castro Carpeno, Javier
Di Noia, Vincenzo
Parra, Hector Soto
Streich, Guillermo
Lee, Dae Ho
Shum, Elaine
Han, Ji-Youn
Jaime, Jesus Corral
Brungs, Daniel
John, Thomas
D'Arcangelo, Manolo
Joaquin, Andres Barba
Liu, Geoffrey
Antonuzzo, Lorenzo
Hinojal, Gonzalo Fernández
Le, Xiuning
Zheng, Li
Jänne, Pasi A
Abstract
WU-KONG1B (ClinicalTrials.gov identifier: NCT03974022) is a multinational phase II, dose-randomized study to assess the antitumor efficacy of sunvozertinib in pretreated patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor () exon 20 insertion mutations (exon20ins).
Eligible patients with advanced-stage exon20ins NSCLC were randomly assigned by 1:1 ratio to receive sunvozertinib 200 mg or 300 mg once daily (200 and 300 mg-rand cohorts). After predefined interim analysis, additional patients were enrolled and treated with the 300 mg dose once daily. The primary end point was blinded independent review committee (IRC)-assessed confirmed objective response rate (cORR), and the key secondary end point was duration of response (DoR).
Among 85, 89, and 107 efficacy-evaluable patients in 200 mg-rand, 300 mg-rand, and 300 mg-all (including randomly assigned and nonrandomized patients) cohorts, the cORRs were 45.9% (97.5% CI, 33.6% to 58.5%), 47.2% (97.5% CI, 35.1% to 59.5%), and 45.8% (97.5% CI, 34.8% to 57.0%), respectively, per IRC assessment. The predefined null hypothesis was rejected with statistical significance ( < .0001). Comparing 300 and 200 mg-rand cohorts, higher cORRs were observed in patients with baseline brain metastasis (52.4% 28.6%) and previous amivantamab treatment (41.7% 25%), as well as longer DoR (13.8 11.1 months). At 200 and 300 mg once daily, the most common treatment-related adverse events with grade ≥3 included diarrhea (2.2% 18%), blood creatine phosphokinase increased (6.6% 12.6%), and anemia (4.4% 6.3%).
Sunvozertinib is efficacious at both 200 and 300 mg once daily in treating platinum-pretreated patients with advanced exon20ins NSCLC. The treatment-related adverse events of sunvozertinib were consistent with an EGFR tyrosine kinase inhibitor, with a more favorable safety profile at 200 mg than 300 mg once daily.
SDGs
Type
journal article