Amivantamab Plus Lazertinib in Patients With EGFR-mutant Non-small Cell Lung Cancer (NSCLC) After Progression on Osimertinib and Platinum-based Chemotherapy: Results From CHRYSALIS-2 Cohort A.
Benjamin Besse, Koichi Goto, Yongsheng Wang, Se-Hoon Lee, Melina E Marmarelis, Yuichiro Ohe, Reyes Bernabe Caro, Dong-Wan Kim, Jong-Seok Lee, Sophie Cousin, Eiki Ichihara, Yongsheng Li, Luis Paz-Ares, Akira Ono, Rachel E Sanborn, Naohiro Watanabe, Maria Jose de Miguel, Carole Helissey, Catherine A Shu, Alexander I Spira, Pascale Tomasini, James Chih-Hsin Yang, Yiping Zhang, Enriqueta Felip, Frank Griesinger, Saiama N Waqar, Antonio Calles, Joel W Neal, Christina S Baik, Pasi A Jänne, S Martin Shreeve, Joshua C Curtin, Bharvin Patel, Michael Gormley, Xuesong Lyu, Jun Chen, Pei-Ling Chu, Janine Mahoney, Leonardo Trani, Joshua M Bauml, Meena Thayu, Roland E Knoblauch, Byoung Chul Cho
Author Information
Benjamin Besse: Paris-Saclay University, Institut Gustave Roussy, Villejuif, France.
Koichi Goto: National Cancer Center Hospital East, Kashiwa, Japan.
Yongsheng Wang: Institute of Clinical Trial Center and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Se-Hoon Lee: Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Melina E Marmarelis: University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, United States.
Yuichiro Ohe: National Cancer Center Hospital, Tokyo, Japan.
Reyes Bernabe Caro: Hospital Universitario Virgen Del Rocio, Seville, Spain.
Dong-Wan Kim: Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea.
Jong-Seok Lee: Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea.
Sophie Cousin: Institut Bergonié, Bordeaux, France.
Eiki Ichihara: Center for Clinical Oncology, Okayama University Hospital, Okayama, Japan.
Yongsheng Li: Chongqing University Cancer Hospital, Chongqing, China.
Luis Paz-Ares: Hospital Universitario 12 de Octubre, Madrid, Spain.
Akira Ono: Shizuoka Cancer Center, Shizuoka, Japan.
Rachel E Sanborn: Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, United States.
Naohiro Watanabe: Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan.
Maria Jose de Miguel: START Madrid-CIOCC, Hospital HM Sanchinarro, Madrid, Spain.
Carole Helissey: Clinical Research unit, Military Hospital Begin, Saint-Mandé, France.
Catherine A Shu: Columbia University Medical Center, New York, NY, United States.
Alexander I Spira: Virginia Cancer Specialists, Fairfax, VA, United States.
Pascale Tomasini: Aix Marseille University - CNRS, INSERM, CRCM; CEPCM - AP-HM Hopital de La Timone, Marseille, France.
James Chih-Hsin Yang: National Taiwan University Cancer Center, Taipei, Taiwan.
Yiping Zhang: Zhejiang Cancer Hospital, Hangzhou, China.
Enriqueta Felip: Medical Oncology Service, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital Campus, Universitat Autonoma de Barcelona Barcelona, Spain.
Frank Griesinger: Pius-Hospital, University Medicine of Oldenburg, Oldenburg, Germany.
Saiama N Waqar: Division of Oncology, Washington University School of Medicine, St. Louis, MO, United States.
Antonio Calles: Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Joel W Neal: Stanford University Medical Center, Stanford, CA, United States.
Christina S Baik: University of Washington, Fred Hutchinson Cancer Center, Seattle, WA, United States.
Pasi A Jänne: Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Boston, MA, United States.
S Martin Shreeve: Janssen Research & Development, San Diego, CA, United States.
Joshua C Curtin: Janssen Research & Development, Spring House, PA, United States.
Bharvin Patel: Janssen Research & Development, Spring House, PA, United States.
Michael Gormley: Janssen Research & Development, Spring House, PA, United States.
Xuesong Lyu: Janssen Research & Development, Shanghai, China.
Jun Chen: Janssen Research & Development, Spring House, PA, United States.
Pei-Ling Chu: Janssen Research & Development, Raritan, NJ, United States.
Janine Mahoney: Janssen Research & Development, Spring House, PA, United States.
Leonardo Trani: Janssen Research & Development, Spring House, PA, United States.
Joshua M Bauml: Janssen Research & Development, Spring House, PA, United States.
Meena Thayu: Janssen Research & Development, Spring House, PA, United States.
Roland E Knoblauch: Janssen Research & Development, Spring House, PA, United States.
Byoung Chul Cho: Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: CBC1971@yuhs.ac.
INTRODUCTION: Treatment options for patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) with disease progression on/after osimertinib and platinum-based chemotherapy are limited. METHODS: CHRYSALIS-2 Cohort A evaluated amivantamab+lazertinib in patients with EGFR exon 19 deletion- or L858R-mutated NSCLC with disease progression on/after osimertinib and platinum-based chemotherapy. Primary endpoint was investigator-assessed objective response rate (ORR). Patients received intravenous amivantamab 1050 mg (1400 mg if ≥80 kg) plus oral lazertinib 240 mg. RESULTS: In Cohort A (n=162), investigator-assessed ORR was 28% (95% CI, 22-36). Blinded independent central review (BICR)-assessed ORR was 35% (95% CI, 27-42), with median duration of response (DoR) of 8.3 months (95% CI, 6.7-10.9) and clinical benefit rate of 58% (95% CI, 50-66). At a median follow-up of 12 months, 32/56 responders (57%) achieved a DoR ≥6 months. Median progression-free survival by BICR was 4.5 months (95% CI, 4.1-5.8); median overall survival was 14.8 months (95% CI, 12.2-18.0). Preliminary evidence of central nervous system-anti-tumor activity was reported among 7 patients with baseline brain lesions and no prior brain radiation/surgery. Exploratory biomarker analyses using circulating tumor DNA next-generation sequencing showed responses in patients with and without identified EGFR/MET-dependent resistance. Most frequent adverse events were rash (grouped term; 81%), infusion-related reaction (68%), and paronychia (52%). Most common grade ≥3 treatment-related adverse events were rash (grouped term; 10%), infusion-related reaction (9%), and hypoalbuminemia (6%). CONCLUSIONS: For patients with limited treatment options, amivantamab+lazertinib demonstrated anti-tumor activity with a safety profile characterized by EGFR/MET-realated adverse events, which were generally manageable.
