TY - JOUR
T1 - 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)
AU - Yang, James Chih Hsin
AU - Wang, Mengzhao
AU - Doucet, Ludovic
AU - Fan, Yun
AU - Lv, Dongqing
AU - Sun, Meili
AU - Huang, Dingzhi
AU - Greillier, Laurent
AU - Planchard, David
AU - Hong, Qunying
AU - Mazieres, Julien
AU - Felip, Enriqueta
AU - Li, Xingya
AU - Hu, Ying
AU - Fang, Jian
AU - Bazhenova, Lyudmila
AU - Ghiringhelli, François
AU - Cobo Dols, Manuel Angel
AU - Rodriguez, Luis Paz Ares
AU - Bearz, Alessandra
AU - Pellini, Bruna
AU - Kim, Yu Jung
AU - Bosch-Barrera, Joaquim
AU - Shim, Byoung Yong
AU - Luo, Yung Hung
AU - Tiseo, Marcello
AU - Yang, Tsung Ying
AU - Carcereny, Enric
AU - Memmott, Regan M.
AU - Zalcman, Gerard
AU - de Castro Carpeno, Javier
AU - Di Noia, Vincenzo
AU - Parra, Hector Soto
AU - Streich, Guillermo
AU - Lee, Dae Ho
AU - Shum, Elaine
AU - Han, Ji Youn
AU - Jaime, Jesus Corral
AU - Brungs, Daniel
AU - John, Thomas
AU - D'Arcangelo, Manolo
AU - Joaquin, Andres Barba
AU - Liu, Geoffrey
AU - Antonuzzo, Lorenzo
AU - Hinojal, Gonzalo Fernández
AU - Le, Xiuning
AU - Zheng, Li
AU - Jänne, Pasi A.
N1 - Publisher Copyright:
© 2025 American Society of Clinical Oncology
PY - 2025/11/19
Y1 - 2025/11/19
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/105015518285
U2 - 10.1200/JCO-25-00788
DO - 10.1200/JCO-25-00788
M3 - Article
C2 - 40923280
AN - SCOPUS:105015518285
SN - 0732-183X
VL - 43
SP - 3198
EP - 3208
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 29
ER -
SDG 3 Good Health and Well-being