New Pill Offers Hope for Patients With Hard-to-Treat Lung Cancer Mutation

A new targeted therapy has shown promise for a difficult-to-treat subset of lung cancer. In a multinational phase 2 trial, the oral drug sunvozertinib produced durable tumor responses in patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations, according to research published Sept. 9 in the Journal of Clinical Oncology. The findings supported the FDA’s July 2025 decision to grant the drug, marketed as Zegfrovy and manufactured by Dizal Pharmaceutical Co., Ltd., accelerated approval for this use.

EGFR exon 20 insertion mutations make up only a small share of NSCLC cases, amounting to approximately 2% to 3% of the cases overall and roughly 12% of all EGFR-related tumors. NSCLC cases with mutations are especially tough to treat and have historically been linked with poorer outcomes on standard chemotherapy. Platinum-based chemo regimens remain the usual first step, but response rates are modest and the benefit often lasts just a few months. Last year, the FDA approved Rybrevant (amivantamab) with chemotherapy as a first-line intravenous treatment option. However, patients are left with limited choices if their disease progresses.

To address this unmet need, James Chih-Hsin Yang, M.D., Ph.D., of National Taiwan University Cancer Center, and colleagues conducted the WU-KONG1B clinical trial. The researchers randomly assigned patients with platinum-pretreated NSCLC carrying EGFR exon 20 insertions to receive sunvozertinib at 200 milligrams (mg) or 300 mg once daily. The primary end point was confirmed objective response rate as assessed by independent review, with duration of response as a key secondary endpoint.

Among 85 evaluable patients in the 200-mg cohort and 89 in the 300-mg group, response rates were 45.9% and 47.2%, respectively. A pooled analysis of all 107 patients treated at 300 mg showed a similar response rate of 45.8%. Median duration of response reached 13.8 months with 300 mg compared with 11.1 months with 200 mg. Patients with baseline brain metastases or prior exposure to Rybrevant appeared to derive greater benefit at the higher dose, with response rates exceeding 40% to 50%.

Treatment was generally manageable, though side effects were more likely at the higher dose. The most common grade 3 or higher adverse events included diarrhea, elevated creatine phosphokinase and anemia. Investigators concluded that both doses were active, with 200 mg offering a more favorable safety profile.

Based on these results, the FDA approved the drug at a recommended dose of 200 mg once daily for adults with locally advanced or metastatic NSCLC harboring EGFR exon 20 insertions whose disease has progressed after platinum chemotherapy. The agency also approved a companion diagnostic test to identify eligible patients.

As with other accelerated approvals, full approval will depend on confirmation of clinical benefit in ongoing phase 3 trials, including the WU-KONG28 study comparing Zegfrovy with chemotherapy in the first-line setting.

“Sunvozertinib demonstrates clinical activity and should be considered as a second-line treatment option,” wrote JCO’s Associate Editor Thomas Stinchcombe, M.D., in an accompanying

The FDA’s nod for Zegfrovy comes about 16 months after the agency approved Johnson & Johnson’s infused therapy Rybrevant in combination with chemotherapy as a first-line treatment for EGFR exon 20 insertion-positive NSCLC. As a once-daily oral tablet, Zegfrovy represents a different approach as a selective EGFR tyrosine kinase inhibitor. Together, the two therapies highlight a growing set of tools for tackling a rare but challenging cancer subtype.