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)
James Chih‐Hsin Yang, Mengzhao Wang, Ludovic Doucet, Yun Fan, Dongqing Lv, Meili Sun, Dingzhi Huang, Laurent Greillier, David Planchard, Qunying Hong, Julien Mazières, Enriqueta Felip, Xingya Li, Ying Hu, Jian Fang, Lyudmila Bazhenova, François Ghiringhelli, Manuel Angel Cobo Dols, Luis Paz‐Ares, Alessandra Bearz, Bruna Pellini, Yu Jung Kim, Joaquim Bosch‐Barrera, Byoung Yong Shim, Yung‐Hung Luo, Marcello Tiseo, Tsung‐Ying Yang, Enric Carcereny, Regan M. Memmott, Gérard Zalcman, Javier de Castro Carpeno, Vincenzo Di Noia, Héctor Soto Parrà, Guillermo Streich, Dae Ho Lee, Elaine Shum, Ji-Youn Han, Jesus Corral Jaime, Daniel Brungs, Thomas John, M. D’Arcangelo, A. Barba Joaquín, Geoffrey Liu, Lorenzo Antonuzzo, G. Fernández-Hinojal, Xiuning Le, Li Zheng, Pasi A. Jänne, Guillermo Streich, Karina Vera, Juan Cundom, Daniel Brungs, Thomas John, Geoffrey Liu, Mengzhao Wang, Yun Fan, Dongqing Lv, Meili Sun, Dingzhi Huang, Qunying Hong, Xingya Li, Ying Hu, Jian Fang, Yanqiu Zhao, Kejing Tang, Xia Song, Junqiang Zhang, Yao Yu, Zili Meng, Chengzhi Zhou, Zhangzhou Huang, Shi H, Junzhen Gao, Jianhua Shi, Aiping Zeng, Bin Yang, Anwen Liu, Bo Jin, Yan Yu, Ying Cheng, Jianying Zhou, Lin Wu, Ludovic Doucet, Laurent Greillier, David Planchard, Julien Mazières, François Ghiringhelli, Gérard Zalcman, M. Duruisseaux, Nicolás Isambert, Alexis B. Cortot, Alessandra Bearz, Marcello Tiseo, Vincenzo Di Noia, Héctor Soto Parrà, M. D’Arcangelo, Lorenzo Antonuzzo, Chun SenLim, Yong Kek Pang, Ki Hyeong Lee
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.