FDA approves mobocertinib for NSCLC with EGFR exon 20 insertion mutations

The U.S. Food and Drug Administration (FDA) has granted accelerated approval of  mobocertinib for patients with metastatic non-small cell lung cancer (NSCLC) who have epidermal growth factor receptor (EGFR) exon 20 insertions (exon20ins).1 EGFR exon20ins-positive NSCLC is the third most prevalent EGFR-mutated NSCLC and is more common in non-smokers and people of Asian descent.2

Mobocertinib is a novel, irreversible EFGR tyrosine kinase inhibitor (TKI) designed to target EGFR exon20ins-positive NSCLC and has shown to be more effective than existing EGFR TKIs including afatinib, erlotinib, and gefitinib in these patients. Whilst osimertinib has been assessed in the patients with EGFR exon20ins-positive NSCLC, osimertinib has limited antitumor activity in these patients. Additionally, limited therapeutic options exist for this subset of patients, due to resistance to EGFR TKIs.3,4

This accelerated approval was based on the results of a Phase I/II multicenter, open-label trial (NCT02716116), which investigated the safety, pharmacokinetics, and safety of mobocertinib in patients with EGFR exon20ins-positive metastatic NSCLC. In total, 114 patients who were previously treated with platinum-based therapies were enrolled; the median age of the cohort was 60 years, 60% were Asian, and 66% of patients were female. All patients received 160 mg mobocertinib, with the primary endpoint being confirmed objective response rate (ORR).5

The trial reported a confirmed ORR of 28% (95% CI: 20–37), and a median duration of response (DOR) of 17.5 months (95% CI: 7.4–20.3). Median progression-free survival (PFS) was reported to be 7.3 months (95% CI: 5.5–9.2) and median overall survival was 24 months (95% CI: 14.6, 28.8). Treatment-related adverse events (TRAEs) were reported in more than 20% of the cohort and the most common TRAEs included diarrhea (91%), rash (45%), paronychia (38%), decreased appetite (35%), nausea (34%), dry skin (31%), and vomiting (30%).5

This approval potentially fulfills an unmet need for treating EGFR exon20ins-positive NSCLC, a subtype of lung cancer with previously no targeted therapies available. In an interview with VJOncology, Dr Alexander Spira,  MD, PhD, FACP, Virginia Cancer Specialists, Fairfax, VA, highlights the clinical benefit of approving mobocertinib for patients with EGFR ex20ins-positive NSCLC.

“Mobocertinib has been one of the most exciting drug classes for a while … [EGFR exon 20 insertion mutations] it’s been a very tough area to crack, because it’s a driver mutation. It tends to be seen in non-smokers and younger, healthier people, and the classic EGFR inhibitors have not shown activity. There was one small exception; there was one small study using high-dose osimertinib, that in very small numbers of patients maybe showed a benefit”


  1. FDA grants accelerated approval to mobocertinib for metastatic non-sma [Internet]. U.S. Food and Drug Administration. 2021 [cited 19 September 2021]. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-mobocertinib-metastatic-non-small-cell-lung-cancer-egfr-exon-20
  2. Fang W, Huang Y, Hong S, et al. EGFR exon 20 insertion mutations and response to osimertinib in non-small-cell lung cancer. BMC Cancer. 2019;19(1).
  3. Gonzalvez F, Vincent S, Baker T, et al. Mobocertinib (TAK-788): A Targeted Inhibitor of EGFR Exon 20 Insertion Mutants in Non–Small Cell Lung Cancer. Cancer Discovery. 2021;11(7):1672-1687.
  4. Inagaki Y, Tamiya A, Matsuda Y, et al. Poor effect of osimertinib on EGFR exon 20 insertion-positive lung adenocarcinoma. Medicine. 2020;99(42):e22628.
  5. Ramalingam S, Zhou C, Kim T, et al. Mobocertinib (TAK-788) in EGFR exon 20 insertion (ex20ins)+ metastatic NSCLC (mNSCLC): Additional results from platinum-pretreated patients (pts) and EXCLAIM cohort of phase 1/2 study. Journal of Clinical Oncology. 2021;39(15_suppl):9014-9014.

Written by Simon Ng