The U.S. Food and Drug Administration (FDA) has approved sevabertinib, an oral targeted therapy, for adult patients with non-small-cell lung cancer (NSCLC) whose tumors harbor certain HER2 (ERBB2) mutations and who have previously received chemotherapy or immunotherapy. The approval reflects a multiyear collaboration led by Dana-Farber Cancer Institute investigators, working closely with colleagues at the Broad Institute.
Matthew Meyerson, MD, PhD
“This is an important step forward for patients,” said Matthew Meyerson, MD, PhD, the Charles A. Dana Chair in Human Cancer Genetics at Dana-Farber Cancer Institute, Professor of Genetics and Medicine at Dana-Farber and Harvard Medical School, and an institute member at the Broad Institute. “So hopefully this will prove to be of benefit for patients with ERBB2 mutant lung cancers, and perhaps for some other indications as well.”
Mechanism of Action
Sevabertinib is an oral targeted medicine designed to block abnormal HER2 signals that drive tumor growth. It also affects a related pathway, EGFR, while largely sparing the normal form of EGFR—an approach intended to help limit side effects. It offers a new option for a patient population estimated at roughly 4,000 to 8,000 people in the United States each year, many of whom are women, including younger women who have never smoked.
The FDA’s decision is supported by clinical studies showing that sevabertinib can shrink tumors and keep disease under control. In these studies, more than half of patients saw their tumors shrink, and in one study group the response rate was over 70%; about 80% had their disease stabilized or reduced. Sevabertinib received Breakthrough Therapy designation in 2024 and received Priority Review in 2025. A large, ongoing clinical trial is now testing sevabertinib as a first-line treatment for patients with HER2-mutant NSCLC, and researchers are also studying the agent in other solid tumors with HER2 mutations.
The approval builds on discoveries made nearly 2 decades ago at Dana-Farber and the Broad Institute. In 2005, research led by Meyerson and collaborators identified a specific genetic change in the EGFR gene, an “exon 20 insertion” that helped explain why some lung cancers resist available treatments. That insight paved the way for designing medicines that precisely target similar activating mutations in HER2. Researchers in Meyerson’s lab, and senior colleagues at the Broad Institute, then advanced sevabertinib to target these HER2 mutations.
