Zipalertinib in Patients With Epidermal Growth Factor Receptor Exon 20 Insertion-Positive Non–Small Cell Lung Cancer Previously Treated With Platinum-Based Chemotherapy With or Without Amivantamab
Abstract
PURPOSE To evaluate the safety and efficacy of zipalertinib, an irreversible epidermal growth factor receptor (EGFR) inhibitor, in pretreated patients with non–small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion (ex20ins) mutations. METHODS REZILIENT1 (ClinicalTrials.gov identifier: NCT04036682 ) is a phase I/II open-label trial enrolling patients with locally advanced or metastatic EGFR ex20ins-mutant NSCLC previously treated with platinum-based chemotherapy with/without ex20ins-targeted therapies. Asymptomatic, treated and untreated stable CNS metastases are permitted. We report data from patients treated with zipalertinib 100 mg twice daily. The primary end points are objective response rate (ORR) and duration of response (DOR) by independent central review. RESULTS At data cutoff (December 10, 2024), 244 patients had received treatment with zipalertinib 100 mg twice daily. The primary efficacy population (8 months' follow-up) comprised patients who had received prior platinum-based chemotherapy without ex20ins-targeted therapy (125 patients), with amivantamab only (30 patients), or with amivantamab and other ex20ins-targeted therapy (21 patients). The confirmed ORR was 35.2% (95% CI, 28.2 to 42.8); median DOR was 8.8 months (95% CI, 8.3 to 12.7). Among patients who received prior platinum-based chemotherapy without ex20ins-targeted therapy, amivantamab only, or amivantamab and other ex20ins-targeted therapy, the confirmed ORR was 40%, 30%, and 14.3%, and median DOR was 8.8, 14.7, and 4.2 months, respectively. Among 68 patients with CNS metastases, the ORR was 30.9%. The most common grade ≥3 treatment-related adverse events were anemia (7%), pneumonitis and rash (2.5% each), and diarrhea, ALT increased, and platelet count decreased (2% each). CONCLUSION Zipalertinib demonstrated clinically meaningful efficacy with a manageable safety profile in patients with EGFR ex20ins-mutant NSCLC who received prior platinum-based chemotherapy with or without amivantamab.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (60)
Ross A. Soo
Department of Hematology–Oncology, National University Cancer Institute, Singapore
Victor Ho-fun Lee
Daniel Shao-Weng Tan
Oscar J. Juan Vidal
Hospital Universitari i Politecnic La Fe, Valencia, Spain
Alexander I. Spira
Virginia Cancer Specialists and NEXT Oncology-Virginia, Fairfax
Gonzalo Fernandez-Hinojal
Clinica Universidad de Navarra, Madrid
Erika K. Keeton
Cullinan Therapeutics, Inc., Cambridge, MA
Zhihui Sunny Yang
Cullinan Therapeutics, Inc., Cambridge, MA
Shengting Li
QingHai Salt Lake Industry Co., Ltd. Golmud 816000 China
Zhiying Cindy Xu
Cullinan Therapeutics, Inc., Cambridge, MA
Jeffrey A. Jones
Cullinan Therapeutics, Inc., Cambridge, MA
Helena Alexandra Yu
Zofia Piotrowska
Helena Yu
Danny Nguyen
Alexander Spira
NEXT Oncology Virgina, Virgina Cancer Specialists Research Institute, Fairfax
John Wrangle
Vamsidhar Velcheti
Mark Socinski
Rachel Sanborn
Gregory Kalemkerian
Nashat Gabrail
6Gabrail Cancer Center, Canton, United States
Ho Fun Victor Lee
Gerrina Ruiter
Department of Clinical Pharmacology, Netherlands Cancer Institute, Amsterdam
Egbert Smit
Daniel Shao Weng Tan
Ross Lai Kit Soo
James Chih-Hsin Yang
National Taiwan University Hospital, NTU Cancer Center, Taipei
Gee-Chen Chang
School of Medicine and Institute of Medicine, Chung Shan Medical University and Division of Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
Tsung-Ying Yang
Department of Chest Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
Chao-Hua Chiu
Haruyasu Murakami
Shizuoka Cancer Center, Shizuoka, Japan
Hiroshi Tanaka
Yasushi Goto
Nishino Kazumi
Ryo Ariyasu
The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
Shigeki Umemura
National Cancer Center Hospital East, Kashiwa, Japan
Haruko Daga
Annalisa Fontana
Lorenzo Antonuzzo
Azienda Ospedaliero Universitaria Careggi, Florence, Italy
Antonio Passaro
Division of Thoracic Oncology, European Institute of Oncology IRCCS, Milan
Oscar Jose Juan-Vidal
Mariano Provencio Pulla
Gonzalo Fernandez Hinojal
Department of Medical Oncology, Clinica Universidad de Navarra, Madrid, Spain
Manual Cobo Dols
Antonio Calles Blanco
Hospital General Universitario Gregorio Marañón, Madrid, Spain
Laura Mezquita Perez
Delvys Rodriguez Abreu
Enriqueta Felip Font
Maria Rosario Garcia Campelo
Ernesto Samuel Nadal Alforia
Tatiana Hernandez
Hyun Woo Lee
Se Hyun Kim
Byoung Yong Shim
Sang-We Kim
Asan Medical Center, Seoul, South Korea
Sung Yong Lee
Young Saing Kim
Gachon University Gil Medical Center, Namdong-Gu, Korea, Republic of
Se-Hoon Lee
Ji-Youn Han