Sunvozertinib Now Available in the US for Previously Treated EGFR Exon 20 Insertion–Mutated NSCLC

October 29, 2026 | OncLive Staff

Sunvozertinib (Zegfrovy) is now commercially available in the United States (US) for adult patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.¹

The FDA granted accelerated approval to the agent in this indication on July 2, 2025, based on findings from Part B of the phase 1/2 WU-KONG1 trial (NCT03974022).^1,2

Findings supporting the approval showed that in the primary efficacy population treated with sunvozertinib at 200 mg once daily (n = 85), the confirmed objective response rate (ORR) was 46% (95% CI, 35%-57%).^1,2 Among responders (n = 39), the median duration of response (DOR) was 11.1 months (95% CI, 8.2-not evaluable), and 72% had a DOR of at least 6 months.¹

“Patients with EGFR exon 20 insertion–mutated [NSCLC] 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. “For these patients, sunvozertinib 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.”

The National Comprehensive Cancer Network lists sunvozertinib as a category 2A subsequent therapy option in this population.

What is the mechanism of action of sunvozertinib?

Sunvozertinib is an oral, irreversible EGFR inhibitor designed to target a broad spectrum of EGFR mutations, including exon 20 insertions, with selectivity over EGFR wild-type. The recommended dose is 200 mg orally once daily with food.

Alongside the 2025 accelerated approval, the FDA cleared the Oncomine Dx Express Test to detect EGFR exon 20 insertion mutations in patients being considered for sunvozertinib.²

How was WU-KONG1 Part B designed?

The multinational, open-label, dose-randomization portion of WU-KONG1 enrolled patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations whose disease progressed on or after platinum-based chemotherapy.^1,2

In part B, patients received sunvozertinib at 200 mg once daily.¹

The primary end point was confirmed ORR by blinded independent review committee per RECIST 1.1 criteria DOR by independent review committee was a key secondary end point.²

What is the safety profile of sunvozertinib?

The prescribing information includes warnings and precautions for interstitial lung disease/pneumonitis, which occurred in 1.7% of patients in the safety population (n = 121); severe gastrointestinal reactions, including diarrhea (73%) and nausea/vomiting (43%); dermatologic reactions, including rash and acneiform dermatitis (68%); ocular toxicity, including keratitis (13%); and embryo-fetal toxicity.¹

Patients of reproductive potential should use effective nonhormonal contraception during treatment and for 2 weeks after the final dose, and concomitant use of strong CYP3A inhibitors and strong or moderate CYP3A inducers should be avoided.

What are the next steps for sunvozertinib?

Findings from the phase 3 WU-KONG28 trial (NCT05668988) presented at the 2026 ASCO Annual Meeting.³ In the trial, patients were randomly assigned to sunvozertinib at 300 mg once daily (n = 163) or carboplatin (area under the curve 5) plus pemetrexed (500 mg/m²) every 3 weeks for up to 6 cycles followed by pemetrexed maintenance (n = 161).

The median progression-free survival by blinded independent central review was 10.3 months (95% CI, 8.3-14.0) with sunvozertinib vs 7.5 months (95% CI, 6.7-8.5) with chemotherapy (HR, 0.65; 95% CI, 0.50-0.85; P = .0008). The confirmed ORR was 58.9% (95% CI, 50.9%-66.5%) vs 31.1% (95% CI, 24.0%-38.8%), respectively.⁴

References

1. 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. AstraZeneca. October 22, 2026. Accessed October 23, 2026. https://www.astrazeneca-us.com/content/az-us/media/press-releases/2026/ZEGFROVY-sunvozertinib-now-available-in-the-US-for-patients-with-previously-treated-non-small-cell-lung-cancer-with-EGFR-exon-20-insertion-mutations.html
2. FDA grants accelerated approval to sunvozertinib for metastatic non-small cell lung cancer with EGFR exon 20 insertion mutations. FDA. July 2, 2025. Accessed October 23, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sunvozertinib-metastatic-non-small-cell-lung-cancer-egfr-exon-20
3. Heymach JV, Liu G, Xing L, et al. Sunvozertinib monotherapy versus platinum-based chemotherapy as first-line treatment for advanced NSCLC with EGFR exon20ins: primary analysis of a multinational phase 3 randomized study (WU-KONG28). J Clin Oncol. 2026;44(suppl 17):LBA8500. doi:10.1200/JCO.2026.44.17_suppl.LBA8500