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)
- Author(s)
- Yang, JCH; Wang, M; Doucet, L; Fan, Y; Lv, D; Sun, M; Huang, D; Greillier, L; Planchard, D; Hong, Q; Mazieres, J; Felip, E; Li, X; Hu, Y; Fang, J; Bazhenova, L; Ghiringhelli, F; Cobo Dols, MA; Paz-Ares Rodriguez, L; Bearz, A; Pellini, B; Kim, YJ; Bosch-Barrera, J; Shim, BY; Luo, YH; Tiseo, M; Yang, TY; Carcereny, E; Memmott, RM; Zalcman, G; de Castro Carpeno, J; Di Noia, V; Soto Parra, H; Streich, G; Lee, DH; Shum, E; Han, JY; Corral Jaime, J; Brungs, D; John, T; D'Arcangelo, M; Barba Joaquin, A; Liu, G; Antonuzzo, L; Fernandez Hinojal, G; Le, X; Zheng, L; Janne, PA;
- Journal Title
- Journal of Clinical Oncology
- Publication Type
- Online publication before print
- Abstract
- PURPOSE: 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 (EGFR) exon 20 insertion mutations (exon20ins). METHODS: Eligible patients with advanced-stage EGFR 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). RESULTS: 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 (P < .0001). Comparing 300 and 200 mg-rand cohorts, higher cORRs were observed in patients with baseline brain metastasis (52.4% v 28.6%) and previous amivantamab treatment (41.7% v 25%), as well as longer DoR (13.8 v 11.1 months). At 200 and 300 mg once daily, the most common treatment-related adverse events with grade ≥3 included diarrhea (2.2% v 18%), blood creatine phosphokinase increased (6.6% v 12.6%), and anemia (4.4% v 6.3%). CONCLUSION: Sunvozertinib is efficacious at both 200 and 300 mg once daily in treating platinum-pretreated patients with advanced EGFR 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.
- Department(s)
- Medical Oncology
- Publisher's Version
- https://doi.org/10.1200/jco-25-00788
- Open Access at Publisher's Site
https://doi.org/10.1200/jco-25-00788- Terms of Use/Rights Notice
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Creation Date: 2025-10-02 01:41:49
Last Modified: 2025-10-02 01:43:42