Amivantamab Plus Lazertinib in Atypical EGFR-Mutated Advanced Non–Small Cell Lung Cancer: Results From CHRYSALIS-2

Author(s): Pascale Tomasini, MD, MSc¹; Yongsheng Wang, MD²; Yongsheng Li, MD, PhD³; Enriqueta Felip, MD, PhD⁴; Lin Wu, MD⁵; Jiuwei Cui, MD, PhD⁶; Benjamin Besse, MD, PhD⁷; Alexander I. Spira, MD, PhD⁸; Joel W. Neal, MD, PhD⁹; Koichi Goto, MD, PhD¹⁰; Christina S. Baik, MD, MPH¹¹; Melina E. Marmarelis, MD¹²; Eiki Ichihara, MD, PhD¹³; Yiping Zhang, MD¹⁴; Jong-Seok Lee, MD, PhD¹⁵; Se-Hoon Lee, MD, PhD¹⁶; James Chih-Hsin Yang, MD, PhD¹⁷; Sebastian Michels, MD¹⁸; Zacharias Anastasiou, MS¹⁹; Joshua C. Curtin, PhD²⁰; Xuesong Lyu, PhD²¹; Janine Mahoney, BSN, RN²⁰; Levon Demirdjian, PhD²²; Craig S. Meyer, MS, PhD, MPH²²; Youyi Zhang, PhD²³; Isabelle Leconte, PhD²⁴; Patricia Lorenzini, MS²⁰; Roland E. Knoblauch, MD, PhD²⁰; Leonardo Trani, MD²⁰; Mahadi Baig, MD²³; Joshua M. Bauml, MD²⁰; Byoung Chul Cho, MD, PhD²⁵;

Source: DOI: 10.1200/JCO-24-02835

Dr. Anjan Patel's Thoughts

The CHRYSALIS-2, the cohort C analysis of patients with atypical EGFR mutations showed meaningful and durable activity. Atypical mutations can be difficult to deal with as a clinician, and having concrete data on these (S768I, L861Q and G719ZX) mutations gives assurance that this doublet is active. Overall response rate (ORR) was 52% and median progression-free survival (PFS) was 11.1 months in refractory patients and 19.5 months in the treatment-naive population.

PURPOSE

For patients with advanced non–small cell lung cancer (NSCLC) harboring atypical epidermal growth factor receptor (EGFR) mutations (eg, S768I, L861Q, G719X), efficacy of current treatment options is limited.

PATIENTS AND METHODS

CHRYSALIS-2 Cohort C enrolled participants with NSCLC harboring atypical EGFR mutations (G719X, S768I, L861Q, etc) and ≤2 previous lines of therapy. Participants were treatment-naïve or previously received first- or second-generation EGFR tyrosine kinase inhibitors. Coexisting exon 20 insertions, exon 19 deletions, or exon 21 L858R mutations were exclusionary. Participants received 1,050 mg (1,400 mg if ≥80 kg) intravenous amivantamab once weekly for the first 4 weeks and then once every 2 weeks plus 240 mg oral lazertinib once daily. The primary end point was investigator-assessed objective response rate (ORR).

RESULTS

As of January 12, 2024, 105 participants received amivantamab-lazertinib. Most common atypical mutations were G719X (56%), L861X (26%), and S768I (23%), including single and compound mutations. In the overall population (median follow-up: 16.1 months), the ORR was 52% (95% CI, 42 to 62). The median duration of response (mDoR) was 14.1 months (95% CI, 9.5 to 26.2). The median progression-free survival (mPFS) was 11.1 months (95% CI, 7.8 to 17.8); median overall survival (mOS) was not estimable (NE; 95% CI, 22.8 to NE). Adverse events were consistent with previous studies and primarily grade 1 and 2. Among treatment-naïve participants, the ORR was 57% (95% CI, 42 to 71). The mPFS was 19.5 months (95% CI, 11.2 to NE), the mDoR was 20.7 months (95% CI, 9.9 to NE), and mOS was NE (95% CI, 26.3 to NE). Solitary or compound EGFR mutations had no major impact on ORR. The ORR in participants with P-loop and αC-helix compressing, classical-like, and T790M-like mutations was 45% (n = 38), 64% (n = 14), and 67% (n = 3), respectively.

CONCLUSION

In participants with atypical EGFR-mutated advanced NSCLC, amivantamab-lazertinib demonstrated clinically meaningful antitumor activity with no new safety signals.

Author Affiliations

¹Aix Marseille University – CNRS, INSERM, CRCM; CEPCM – AP-HM Hôpital de La Timone, Marseille, France; ²Division of Thoracic Tumor Multimodality Treatment, Cancer Center and Clinical Trial Center, West China Hospital, Sichuan University, Chengdu, China; ³Chongqing University Cancer Hospital, Chongqing, China; ⁴Medical Oncology Service, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain; ⁵Department of Thoracic Medical Oncology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China; ⁶The First Hospital of Jilin University, Changchun, China; ⁷Paris-Saclay University, Institut Gustave Roussy, Villejuif, France; ⁸Virginia Cancer Specialists, Fairfax, VA; ⁹Stanford Cancer Institute, Stanford University, Stanford, CA; ¹⁰National Cancer Center Hospital East, Kashiwa, Japan; ¹¹University of Washington Fred Hutchinson Cancer Research Center, Seattle, WA; ¹²Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; ¹³Center for Clinical Oncology, Okayama University Hospital, Okayama, Japan; ¹⁴Zhejiang Cancer Hospital, Hangzhou, China; ¹⁵Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea; ¹⁶Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; ¹⁷National Taiwan University Cancer Center, Taipei, Taiwan; ¹⁸Department I for Internal Medicine, Faculty of Medicine and University Hospital Cologne, Lung Cancer Group Cologne, Center for Integrated Oncology Aachen Köln Bonn Düsseldorf, University of Cologne, Cologne, Germany; ¹⁹Johnson & Johnson, Athens, Greece; ²⁰Johnson & Johnson, Spring House, PA; ²¹Johnson & Johnson, Shanghai, China; ²²Johnson & Johnson, Brisbane, CA; ²³Johnson & Johnson, Raritan, NJ; ²⁴Johnson & Johnson, Allschwil, Switzerland; ²⁵Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea

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