Mobocertinib in Patients with EGFR Exon 20 Insertion-Positive Non-Small Cell Lung Cancer (MOON): An International Real-World Safety and Efficacy Analysis

Oliver Illini, Felix Carl Saalfeld, Petros Christopoulos, Michaël Duruisseaux, Anders Vikström, Nir Peled, Ingel Demedts, Elizabeth Dudnik, Anna Eisert, Sayed M S Hashemi, Urska Janzic, Waleed Kian, Katja Mohorcic, Saara Mohammed, Maria Silvoniemi, Sacha I Rothschild, Christian Schulz, Claas Wesseler, Alfredo Addeo, Karin ArmsterMalinda Itchins, Marija Ivanović, Diego Kauffmann-Guerrero, Jussi Koivunen, Jonas Kuon, Nick Pavlakis, Berber Piet, Martin Sebastian, Janna-Lisa Velthaus-Rusik, Luciano Wannesson, Marcel Wiesweg, Robert Wurm, Corinna Albers-Leischner, Daniela E Aust, Melanie Janning, Hannah Fabikan, Sylvia Herold, Anna Klimova, Sonja Loges, Yana Sharapova, Maret Schütz, Christoph Weinlinger, Arschang Valipour, Tobias Raphael Overbeck, Frank Griesinger, Marko Jakopovic, Maximilian J Hochmair, Martin Wermke

Research output: Journal article (peer-reviewed)Journal article


EGFR exon 20 (EGFR Ex20) insertion mutations in non-small cell lung cancer (NSCLC) are insensitive to traditional EGFR tyrosine kinase inhibitors (TKIs). Mobocertinib is the only approved TKI specifically designed to target EGFR Ex20. We performed an international, real-world safety and efficacy analysis on patients with EGFR Ex20-positive NSCLC enrolled in a mobocertinib early access program. We explored the mechanisms of resistance by analyzing postprogression biopsies, as well as cross-resistance to amivantamab. Data from 86 patients with a median age of 67 years and a median of two prior lines of treatment were analyzed. Treatment-related adverse events (TRAEs) occurred in 95% of patients. Grade ≥3 TRAEs were reported in 38% of patients and included diarrhea (22%) and rash (8%). In 17% of patients, therapy was permanently discontinued, and two patients died due to TRAEs. Women were seven times more likely to discontinue treatment than men. In the overall cohort, the objective response rate to mobocertinib was 34% (95% CI, 24-45). The response rate in treatment-naïve patients was 27% (95% CI, 8-58). The median progression-free and overall survival was 5 months (95% CI, 3.5-6.5) and 12 months (95% CI, 6.8-17.2), respectively. The intracranial response rate was limited (13%), and one-third of disease progression cases involved the brain. Mobocertinib also showed antitumor activity following EGFR Ex20-specific therapy and vice versa. Potential mechanisms of resistance to mobocertinib included amplifications in MET, PIK3CA, and NRAS. Mobocertinib demonstrated meaningful efficacy in a real-world setting but was associated with considerable gastrointestinal and cutaneous toxicity.

Original languageEnglish
Article number3992
JournalInternational Journal of Molecular Sciences
Issue number7
Publication statusPublished - 03 Apr 2024


  • Male
  • Humans
  • Female
  • Aged
  • Carcinoma, Non-Small-Cell Lung/drug therapy
  • Lung Neoplasms/drug therapy
  • ErbB Receptors/genetics
  • Exons
  • Aniline Compounds
  • Indoles
  • Pyrimidines


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