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)
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.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (83)
Regan M. Memmott
Ohio State University Brain and Spine Hospital, Columbus
Li Zheng
Dizal Pharmaceutical, Shanghai
Guillermo Streich
Karina Vera
Hospital Britanico de Buenos Aires, Buenos Aires, Argentina
Juan Cundom
Daniel Brungs
Medical Oncology, Cancer Care Wollongong and Graduate School of Medicine, University of Wollongong, Wollongong, Australia
Thomas John
Experimental Physics
Geoffrey Liu
Mengzhao Wang
Peking Union Medical College Hospital, Beijing
Yun Fan
Zhejiang Cancer Hospital, Hangzhou, China
Dongqing Lv
Taizhou Hospital of Zhejiang Province, Taizhou, China
Meili Sun
Central Hospital Affiliated to Shandong First Medical University, Jinan, China
Dingzhi Huang
Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
Qunying Hong
ZhongShan Hospital, Fudan University, Shanghai
Xingya Li
Department of Medical Oncology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Ying Hu
Jian Fang
Yanqiu Zhao
Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
Kejing Tang
1State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China, Tianjin, China
Xia Song
Department of Biomedical Engineering College of Design and Engineering National University of Singapore Singapore Singapore
Junqiang Zhang
Yu Yao
Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Institute of Fine Chemicals, School of Chemistry and Molecular Engineering
Zili Meng
Chengzhi Zhou
State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory Disease National Center for Respiratory Medicine Guangzhou Institute of Respiratory Health Guangzhou China
Zhangzhou Huang
Department of Thoracic Medical Oncology, Fujian Cancer Hospital, Fuzhou, China
Huashan Shi
Junzhen Gao
Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
Jianhua Shi
Aiping Zeng
Medical Oncology of Respiratory Medicine, Guangxi Medical University Cancer Hospital, Nanning, China
Bin Yang
Anwen Liu
Bo Jin
Joint International Center for CO2 Capture and Storage (iCCS), Provincial Hunan Key Laboratory for Cost-Effective Utilization of Fossil Fuel Aimed at Reducing Carbon-Dioxide Emissions, Advanced Catalytic Engineering Research Center of the Ministry of Education, College of Chemistry and Chemical Engineering, Hunan University, Lushannan 1, Changsha, Hunan 410082, China
Yan Yu
Department of Respiratory Oncology Harbin Medical University Cancer Hospital Harbin China
Ying Cheng
Institute of Biomedical Research, Yunnan University
Jianying Zhou
The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
Lin Wu
The Department of Thoracic Medical Oncology Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine Central South University Changsha China
Ludovic Doucet
Institut de Cancérologie de L’Ouest, Nantes, France
Laurent Greillier
Assistance Publique–Hôpitaux de Marseille, Hôpital Nord, Marseille, France
David Planchard
Julien Mazières
Centre Hospitalier Universitaire de Toulouse, Université Paul Sabatier, Toulouse, France
François Ghiringhelli
Gérard Zalcman
Arnaud Scherpereel, MD, PhD, CHU Lille, Univ. Lille, Inserm, U1366-UMR9020—CRCLille—Cancer Research Center of Lille, OncoThAI, ONCOLille, Lille, France; Aaron S. Mansfield, MD, Mayo Clinic, Rochester, MN; Francesco Grossi, MD, Medical Oncology Division, Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy; Sanjay Popat, PhD, FRCP, The Royal Marsden Hospital, London, United Kingdom; Paul Baas, MD, PhD, The Netherlands Cancer Institute and Leiden University Medical Center, Amsterdam, the Netherlands; Anna K. Nowak, PhD, MBBS, University of Western Australia, Perth, WA, Australia; Anne S. Tsao, MD, MBA, University of Texas MD Anderson Cancer Center, Houston, TX; Nobukazu Fujimoto, MD, PhD, Okayama Rosai Hospital, Okayama, Japan; Solange Peters, MD, PhD, Lausanne University Hospital, Lausanne, Switzerland; Yolanda Bautista Aragon, MD, Centro Médico Nacional Siglo XXI, Mexico City, Mexico; Toby Talbot, MD, The Sunrise Centre, Royal Cornwall Hospitals NHS Trust, Truro, Unite...
Michaël Duruisseaux
Respiratory Department and Early Phase (EPSILYON), Louis Pradel Hospital, Hospices Civils de Lyon Cancer Institute, Lyon, France
Nicolas Isambert
Alexis Cortot
Alessandra Bearz
CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy
Marcello Tiseo
Vincenzo Di Noia
IRCCS Regina Elena National Cancer Institute, Rome, Italy
Hector Soto Parra
Azienda Ospedaliero—Universitaria “Policlinico—Vittorio Emanuele”, Catania, Italy
Manolo D'Arcangelo
Onco-Hematology Department, Santa Maria delle Croci Hospital, Ravenna, Italy
Lorenzo Antonuzzo
Azienda Ospedaliero Universitaria Careggi, Florence, Italy
Chun SenLim
Yong Kek Pang
Ki Hyeong Lee
Chungbuk National University Hospital, Cheongju-si, North Chungcheong, Cheongju, South Korea
Tae Min Kim
Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
Yu Jung Kim
Byoung-Yong Shim
The Catholic University of Korea, St Vincent's Hospital, Gyeonggi-do, South Korea
Dae Ho Lee
Ji-Youn Han
Enriqueta Felip
Medical Oncology Service, Vall d’Hebron Institute of Oncology, Vall d’Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona
Manuel Angel Cobo Dols
Hospital Regional Universitario de Málaga, Madrid, Spain
Luis Paz-Ares Rodríguez
Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid
Joaquim Bosch-Barrera
Enric Carcereny
Catalan Institute of Oncology, Hospital Germans Trias i Pujol, IGTP. Medical Oncology, Badalona, Spain
Javier de Castro Carpeño
Hospital Universitario HM Madrid Sanchinarro, Madrid, Spain
Jesus Corral Jaime
Hospital Universitario de Jerez, Cádiz, Spain
Andres Barba Joaquin
Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Gonzalo Fernandez Hinojal
Department of Medical Oncology, Clinica Universidad de Navarra, Madrid, Spain
Pilar Garrido Lopez
David Vicente Baz
Manuel Domine Gomez
Maria-Jose de Miguel-Luken
James Chih-Hsin Yang
National Taiwan University Hospital, NTU Cancer Center, Taipei
Yung-Hung Luo
National Taiwan University Hospital, Taipei, Taiwan
Tsung-Ying Yang
Department of Chest Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
Ping-Chih Hsu
Chien-Chung Lin
Pasi A. Jänne
Lyudmila Bazhenova
University of California, San Diego, San Diego, CA, US
Bruna Pellini
Regan Michelle Memmott
Department of Internal Medicine, The Ohio State University - James Comprehensive Cancer Center, Columbus, OH
Elaine Shum
Xiuning Le
Department of Thoracic/Head and Neck Medical Oncology The University of Texas MD Anderson Cancer Center Houston Texas USA