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FDA approves sunvozertinib for non-small cell lung cancer with EGFR Ex20Ins

On July 2 2025, the U.S Food and Drug Administration (FDA) approved sunvozertinib, an oral, irreversible mutant EGFR-selective tyrosine kinase inhibitor (TKI) for adults with non-small cell lung cancer (NSCLC) that possess EGFR exon 20 insertion mutations (EGFR Ex20Ins), and whose disease has progressed despite platinum-based chemotherapy.1

NSCLC accounts for approximately 85% of lung cancer cases, with EGFR Ex20Ins mutations being the third most common type of EGFR mutation, occurring in 10% of NSCLC cases.2 However, patients with NSCLC harboring EGFR Ex20Ins mutations derive minimal to no benefit from current immunotherapy and combined targeted therapies.3 These mutations, thus, associated with poorer patient prognosis, low response rates, and short progression-free survival compared to other EGFR mutations.4 These limitations underscore a need for newer agents that address the resistance associated with EGFR Ex20Ins whilst maintaining a tolerable and favorable safety profile.

The FDA approval was supported by the Phase III multinational WU-KONG1 Part B study (NCT03974022) which evaluated sunvozertinib in 111 patients with EGFR Ex20Ins NSCLC across Asia, Europe, North America, and South America.1 Researchers assessed the efficacy of sunvozertinib at 200 mg and 300 mg using randomized 1:1 dose allocation. The primary endpoint, overall response rate, confirmed by independent review committee, reached 54.3%, with 2.9% of patients with a confirmed complete response. While the secondary endpoint of durable response was not yet met, 74.6% of responders had an ongoing response. The safety profile of sunvozertinib was concordant with previous studies. No new adverse events (AES) arose, and the most common AEs were grade 1 or 2, including diarrhea and elevated creatine phosphokinase.5

We recently spoke with James Chih-Hsin Yang, MD, MPH, National Taiwan University, Taipei, Taiwan, who shared insights into the safety and future potential of drug, stating that

“The side effect profile of patients receiving 300 milligrams per day was what was expected from prior studies, mainly EGFR class side effects … the discontinuation rate as well as dose interruption were pretty low; therefore, this drug has very high potential to be the drug of choice for patients with exon 20 insertion.”

This FDA approval marks vital progress in the treatment of a subset of patients with NSCLC with limited treatment options and poor outcomes, offering targeted and significantly more effective therapeutic alternative.

References:

  1. Center for Drug Evaluation and Research. FDA grants accelerated approval to sunvozertinib for metastatic non-small cell lung cancer with EGFR exon 20 insertion mutations [Internet]. FDA; [cited 2025 Jul 2]. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sunvozertinib-metastatic-non-small-cell-lung-cancer-egfr-exon-20
  2. Araghi M, Mannani R, Heidarnejad maleki A, Hamidi A, Rostami S, Safa SH, et al. Recent advances in non-small cell lung cancer targeted therapy; an update review. Cancer cell international. 2023;23(1):162.
  3. Lee JM, McNamee CJ, Toloza E, Negrao MV, Lin J, Shum E, et al. Neoadjuvant targeted therapy in resectable NSCLC: current and future perspectives. Journal of Thoracic Oncology. 2023;18(11):1458-77.
  4. Wang F, Li C, Wu Q, Lu H. EGFR exon 20 insertion mutations in non-small cell lung cancer. Translational Cancer Research. 2020;9(4):2982.
  5. Yang JCH, Doucet L, Wang M, Fan Y, Sun M, Laurent Greillier, et al. A multinational pivotal study of sunvozertinib in platinum pretreated non-small cell lung cancer with EGFR exon 20 insertion mutations: Primary analysis of WU-KONG1 study. Journal of Clinical Oncology. 2024 Jun 1;42(16_suppl):8513–3.