Sunvozertinib Now Available in US for EGFR Exon 20 Insertion NSCLC

The oral EGFR inhibitor sunvozertinib (Zegfrovy) is now available in the United States for adults with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations whose disease progressed on or after platinum-based chemotherapy.¹

The FDA granted accelerated approval to sunvozertinib based on the phase 2 WU-KONG1B trial. Among 85 patients receiving the approved 200-mg daily dose, the confirmed overall response rate (ORR) was 46% (95% CI, 35%-57%). Among the 39 responders, the median duration of response (DOR) was 11.1 months (95% CI, 8.2-not estimable), and 72% maintained a response for at least 6 months.^1,2

In the full WU-KONG1B results published in the Journal of Clinical Oncology, the ORR was 45.9% (97.5% CI, 33.6%-58.5%) with 200 mg, 47.2% (97.5% CI, 35.1%-59.5%) among 89 evaluable patients randomized to 300 mg, and 45.8% (97.5% CI, 34.8%-57.0%) across all 107 evaluable patients given 300 mg, rejecting the predefined null hypothesis (P < .0001). Compared with 200 mg, the randomized 300-mg dose produced higher response rates in patients with baseline brain metastases (52.4% vs 28.6%) or prior amivantamab treatment (41.7% vs 25%) and a longer median DOR (13.8 vs 11.1 months).³

“Patients with EGFR exon 20 insertion-mutated lung cancer have historically had limited targeted treatment options, particularly after their disease progresses following platinum-based chemotherapy,” D. Ross Camidge, MD, PhD, director of thoracic oncology at the University of Colorado, stated in a news release.¹ “For these patients, sunvozertinib (ZEGFROVY®) offers an oral, once-daily targeted treatment option that is recommended in clinical practice guidelines – giving patients and clinicians an option when treatment choices have historically been limited.”

Sunvozertinib Safety

In the safety population of 121 patients, interstitial lung disease/pneumonitis occurred in 1.7% and led to discontinuation in 0.8%. Serious gastrointestinal adverse reactions occurred in 1.7%, including grade 3 nausea in 0.8%. Diarrhea occurred in 73% (grade 3, 2.5%), prompting dose interruption or reduction in 5% and permanent discontinuation in 0.8%. Nausea and vomiting occurred in 43% (grade 3, 3.3%), leading to interruption or reduction in 7% and discontinuation in 0.8%.¹

Dermatologic adverse reactions affected 68% of patients, including acneiform dermatitis in 9%; grade 3 events included rash (7%), acneiform dermatitis (0.8%), and pruritus (0.8%). Ocular toxicity occurred in 13%, including keratitis in 0.8%.¹

The most common adverse reactions, each occurring in at least 20% of patients, were diarrhea, rash, decreased appetite, stomatitis, fatigue, nausea, paronychia, vomiting, constipation, musculoskeletal pain, pruritus, dry skin, urinary tract infection, abdominal pain, and decreased weight. The most common grade 3 or 4 laboratory abnormalities were decreased lymphocytes and increased lipase.

In the published data, the most common grade 3 or higher treatment-related adverse events at 200 mg vs 300 mg were diarrhea (2.2% vs 18%), increased blood creatine phosphokinase (6.6% vs 12.6%), and anemia (4.4% vs 6.3%).³

WU-KONG1B Trial Design

The multinational, open-label, dose-randomized WU-KONG1B study (NCT03974022) enrolled patients with platinum-pretreated, locally advanced or metastatic EGFR exon 20 insertion-mutated NSCLC. Patients were randomized 1:1 to 200 mg or 300 mg once daily, with more patients later enrolled at 300 mg. Confirmed ORR by blinded independent central review was the primary end point, and DOR was the key secondary end point.^1,3

First-Line Sunvozertinib Under FDA Review

A supplemental application for first-line use has been submitted to the FDA and China’s Center for Drug Evaluation, both of which granted breakthrough therapy designation. The filing is based on the phase 3 WU-KONG28 trial, in which 324 patients were randomized 1:1 to sunvozertinib 300 mg daily or platinum-doublet chemotherapy. Sunvozertinib improved progression-free survival (PFS) (HR, 0.65; P = .0008), with a median PFS of 10.3 months vs 7.5 months. The best objective response rate was 68.1% vs 35.4%, and median DOR was 11.2 vs 7.1 months.^2,4

“As a leader in treating EGFR-mutated lung cancer, the US launch of Zegfrovy marks an important step forward in our commitment to this patient community,” Mohit Manrao, senior vice president, US Oncology, AstraZeneca, stated in the news release.¹ “People living with EGFR exon 20 insertion-mutated disease have historically had limited targeted treatment options following platinum-based chemotherapy. By making Zegfrovy available in the US, we are bringing an oral, mutation-specific treatment option to a distinct patient population with substantial unmet need.”

References

1. AstraZeneca. ZEGFROVY (sunvozertinib) now available in the US for patients with previously treated non-small cell lung cancer with EGFR exon 20 insertion mutations. News release. October 22, 2026. Accessed October 23, 2026. https://tinyurl.com/4b6j58vt

2. Dizal’s ZEGFROVY (sunvozertinib) receives FDA accelerated approval as the only targeted oral treatment for non-small cell lung cancer with EGFR exon 20 insertion mutations. July 2, 2025. Accessed October 23, 2026. https://tinyurl.com/uzvpuvkc

3. Yang JCH, Jang H, Kim SW, et al. Phase II dose-randomized study of sunvozertinib in platinum-pretreated non-small cell lung cancer with epidermal growth factor receptor exon 20 insertion mutations (WU-KONG1B). J Clin Oncol. 2025;43(29):3198-3208. doi:10.1200/JCO-25-00788

4. Dizal announces phase 3 WU-KONG28 results: ZEGFROVY (sunvozertinib) outperforms platinum-doublet chemotherapy in first-line EGFR exon 20 insertion mutation-positive non-small cell lung cancer. News release. PR Newswire. May 29, 2026. Accessed October 23, 2026. https://tinyurl.com/jbb4e8ya