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Nat. Med., 14 September 2023 | https://doi.org/10.1038/s41591-023-02554-7 Amivantamab plus lazertinib in osimertinib-relapsed EGFR-mutant advanced non-small cell lung cancer: a phase 1 trial

Byoung Chul Cho ^{1 *}, Dong-Wan Kim ², Alexander I. Spira ³, Jorge E. Gomez ⁴, Eric B. Haura ⁵, Sang-We Kim ⁶, Rachel E. Sanborn ⁷, Eun Kyung Cho ⁸, Ki Hyeong Lee ⁹, Anna Minchom ¹⁰, Jong-Seok Lee ¹¹, Ji-Youn Han ¹², Misako Nagasaka ¹³, Joshua K. Sabari ¹⁴, Sai-Hong Ignatius Ou ¹³, Patricia Lorenzini ¹⁵, Joshua M. Bauml ¹⁵, Joshua C. Curtin ¹⁵, Amy Roshak ¹⁵, Grace Gao ¹⁵, John Xie ¹⁵, Meena Thayu ¹⁵, Roland E. Knoblauch ¹⁵ & Keunchil Park ^16,17

¹Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
²Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea.
³Virginia Cancer Specialists Research Institute, US Oncology Research, Fairfax, VA, USA.
⁴Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁵H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
⁶Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
⁷Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.
⁸Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea.
⁹Chungbuk National University Hospital, Cheongju, Republic of Korea.
¹⁰Drug Development Unit, Royal Marsden/Institute of Cancer Research, Sutton, UK.
¹¹Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
¹²National Cancer Center, Gyeonggi-do, Republic of Korea.
¹³University of California Irvine School of Medicine, Chao Family Comprehensive Cancer Center, Orange, CA, USA.
¹⁴New York University School of Medicine, New York, NY, USA.
¹⁵Janssen R&D, Spring House, PA, USA.
¹⁶Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
¹⁷Present address: Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

^*Corresponding author: correspondence to Byoung Chul Cho

Abstract

Patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) often develop resistance to current standard third-generation EGFR tyrosine kinase inhibitors (TKIs); no targeted treatments are approved in the osimertinib-relapsed setting. In this open-label, dose-escalation and dose-expansion phase 1 trial, the potential for improved anti-tumor activity by combining amivantamab, an EGFR-MET bispecific antibody, with lazertinib, a third-generation EGFR TKI, was evaluated in patients with EGFR-mutant NSCLC whose disease progressed on third-generation TKI monotherapy but were chemotherapy naive (CHRYSALIS cohort E). In the dose-escalation phase, the recommended phase 2 combination dose was established; in the dose-expansion phase, the primary endpoints were safety and overall response rate, and key secondary endpoints included progression-free survival and overall survival. The safety profile of amivantamab and lazertinib was generally consistent with previous experience of each agent alone, with 4% experiencing grade ≥3 events; no new safety signals were identified. In an exploratory cohort of 45 patients who were enrolled without biomarker selection, the primary endpoint of investigator-assessed overall response rate was 36% (95% confidence interval, 22–51). The median duration of response was 9.6 months, and the median progression-free survival was 4.9 months. Next-generation sequencing and immunohistochemistry analyses identified high EGFR and/or MET expression as potential predictive biomarkers of response, which will need to be validated with prospective assessment. ClinicalTrials.gov identifier: NCT02609776.

논문정보

형식Research article
게재일2023년 09월 (BRIC 등록일 2023-09-26)
연구진국내(교신)+국외 연구진
분야 의약학 > 종양의학

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