Sunvozertinib Now Available in US for Pretreated EGFR Exon 20+ NSCLC

Sunvozertinib (Zegfrovy), an oral, once-daily EGFR inhibitor, is now commercially 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 has progressed on or after platinum-based chemotherapy, AstraZeneca announced on October 22, 2026.¹

The agent produced a 46% confirmed overall response rate in its pivotal trial, and its labeling carries warnings for interstitial lung disease (ILD)/pneumonitis, gastrointestinal and dermatologic adverse reactions, ocular toxicity, and embryo-fetal toxicity—effects that nurses will help patients recognize and manage at home.^1,2

The FDA granted sunvozertinib accelerated approval for this indication on July 2, 2025, as previously reported by Oncology Nursing News.³ The drug was developed by Dizal Pharmaceutical and is now being launched in the US by AstraZeneca. Continued approval may be contingent on verification and description of clinical benefit in a confirmatory trial.¹

What is sunvozertinib, and which patients are eligible?

Sunvozertinib is an irreversible EGFR inhibitor that targets a wide spectrum of EGFR mutations while maintaining selectivity over wild-type EGFR.¹ Eligible patients must have an EGFR exon 20 insertion detected by an FDA-approved test; the Oncomine Dx Express Test was approved alongside sunvozertinib as a companion diagnostic.³

EGFR exon 20 insertions account for an estimated 10% of EGFR-mutated NSCLC and are associated with primary resistance to earlier-generation EGFR tyrosine kinase inhibitors (TKIs).¹ Real-world data have shown a 5-year overall survival rate as low as 8% in this population.^1,4 Sunvozertinib is included in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for NSCLC as a category 2A recommended subsequent therapy option for patients with EGFR exon 20 insertion–positive advanced or metastatic disease.^1,5

The recommended dose is 200 mg orally once daily with food until disease progression or unacceptable toxicity.² The medication is available through the Zegfrovy Specialty Distribution and Pharmacy network and may also be acquired and dispensed by health systems’ own-use specialty pharmacies.¹

What did the WU-KONG1B trial show?

The approval was based on WU-KONG1B (NCT03974022), a multinational, open-label, dose-randomized phase 2 trial in which patients with platinum-pretreated, locally advanced or metastatic NSCLC with EGFR exon 20 insertions were randomly assigned 1:1 to sunvozertinib 200 mg or 300 mg once daily.^1,3,6 The efficacy population included 85 patients treated at the approved 200-mg dose. Confirmed overall response rate (ORR) and duration of response (DOR) by blinded independent central review were the major efficacy outcome measures.¹

In the 200-mg efficacy population:¹

• The confirmed ORR was 46% (95% CI, 35%-57%).
• Median DOR among the 39 responders was 11.1 months (95% CI, 8.2-not evaluable).
• Of the responders, 72% had a DOR of at least 6 months.

In the full trial report published in the Journal of Clinical Oncology, grade 3 or higher treatment-related diarrhea occurred in 2.2% of patients in the 200-mg cohort vs 18% in the 300-mg cohort; corresponding rates were 6.6% vs 12.6% for increased blood creatine phosphokinase and 4.4% vs 6.3% for anemia.⁶ Investigators reported a more favorable safety profile at 200 mg than at 300 mg once daily. The trial was funded by Dizal Pharmaceutical.⁶

What adverse events should nurses monitor for?

Warnings and precautions are based on a safety population of 121 patients:²

• ILD/pneumonitis occurred in 1.7% of patients and led to discontinuation in 0.8%. Sunvozertinib should be withheld immediately for suspected ILD/pneumonitis and permanently discontinued if it is confirmed.
• Diarrhea occurred in 73% of patients (grade 3, 2.5%), and nausea and vomiting occurred in 43% (grade 3, 3.3%). Taking the drug with food is intended to reduce gastrointestinal adverse reactions, and the label calls for supportive care with antidiarrheals, antiemetics, or fluid replacement as indicated.
• Dermatologic adverse reactions occurred in 68% of patients, including acneiform dermatitis in 9%; grade 3 rash occurred in 7%. Patients should use an alcohol-free emollient cream and avoid irritating skin products, such as those containing retinol, retinoic acid, or benzoyl peroxide.
• Ocular toxicity occurred in 13% of patients, including keratitis in 0.8%. Patients with new or worsening eye symptoms should be referred promptly to an ophthalmologist, and contact lens use should stop until symptoms are evaluated.
• Embryo-fetal toxicity: Females of reproductive potential should use effective nonhormonal contraception during treatment and for 2 weeks after the last dose, because sunvozertinib can render some hormonal contraceptives ineffective. Male patients with female partners of reproductive potential should also use effective contraception during that window, and breastfeeding is not advised during treatment or for 2 weeks after the last dose.

The most common adverse reactions (≥20%) were diarrhea, rash, decreased appetite, stomatitis, fatigue, nausea, paronychia, vomiting, constipation, musculoskeletal pain, pruritus, dry skin, urinary tract infection, abdominal pain, and decreased weight.² Concomitant use with strong CYP3A inhibitors or with strong or moderate CYP3A inducers should be avoided; if it cannot be avoided, the label directs a dose adjustment.²

What’s next for sunvozertinib in the first-line setting?

A supplemental new drug application for first-line use has been submitted to the FDA and to China’s Center for Drug Evaluation, and both agencies have granted breakthrough therapy designation in this setting.¹ The filing is supported by the phase 3 WU-KONG28 trial (NCT05668988), which randomly assigned 324 patients with treatment-naive advanced NSCLC with EGFR exon 20 insertions to sunvozertinib 300 mg once daily or carboplatin and pemetrexed followed by pemetrexed maintenance.^7,8 Results were presented at the 2026 ASCO Annual Meeting and published simultaneously in The New England Journal of Medicine:^7,8

Median progression-free survival 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 < .001).

The ORR was 58.9% vs 31.1%, and median DOR was 11.2 vs 7.1 months.

Serious adverse events were reported in 45.4% vs 26.7% of patients.

Overall survival data were immature, and 90.2% of patients in the chemotherapy arm crossed over to sunvozertinib after progression, which complicates survival interpretation.^7,8 Notably, WU-KONG28 tested a 300-mg dose, whereas the currently approved dose in the pretreated setting is 200 mg.^2,7

Other agents continue to be studied for EGFR exon 20 insertion–positive NSCLC, including zipalertinib, which Oncology Nursing News previously covered in patients whose disease progressed on or after amivantamab (Rybrevant).⁹

What are the key takeaways for oncology nurses?

• Confirm the biomarker. Eligibility requires an EGFR exon 20 insertion detected by an FDA-approved test and progression on or after platinum-based chemotherapy.¹
• Teach “with food, once daily.” The 200-mg dose is taken with food, which is also part of the strategy for reducing gastrointestinal effects.²
• Get ahead of diarrhea and skin toxicity. With diarrhea in 73% and dermatologic reactions in 68% of patients, review antidiarrheal plans, hydration, alcohol-free emollients, and products to avoid before the first dose.²
• Flag pulmonary and eye symptoms early. New or worsening cough, dyspnea, or fever warrants prompt evaluation for ILD/pneumonitis, and new eye symptoms warrant ophthalmology referral.²
• Counsel on contraception and interactions. Nonhormonal contraception is needed during treatment and for 2 weeks after; medication reconciliation should screen for CYP3A inhibitors and inducers.²
• Support access and informed decisions. The drug is dispensed through a specialty distribution and pharmacy network, and patients should understand that the approval is accelerated, based on response rate and DOR.¹

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 22, 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. Zegfrovy. Prescribing information. AstraZeneca Pharmaceuticals LP; 2026. Accessed October 22, 2026. https://drd9vrdh9yh09.cloudfront.net/50fd68b9-106b-4550-b5d0-12b045f8b184/0f19e26e-7da8-49f2-9485-175cf31b3d68/0f19e26e-7da8-49f2-9485-175cf31b3d68_viewable_rendition__v.pdf
3. Hoyt B. Sunvozertinib granted FDA accelerated approval in EGFR exon 20+ NSCLC. Oncology Nursing News. July 2, 2025. Accessed October 22, 2026. https://www.oncnursingnews.com/view/sunvozertinib-granted-fda-accelerated-approval-in-egfr-exon-20-nsclc
4. Bazhenova L, Minchom A, Viteri S, et al. Comparative clinical outcomes for patients with advanced NSCLC harboring EGFR exon 20 insertion mutations and common EGFR mutations. Lung Cancer. 2021;162:154-161.
5. NCCN. Clinical Practice Guidelines in Oncology. Non-small cell lung cancer, version 6.2026. Accessed October 22, 2026. https://www.nccn.org/guidelines
6. Yang JC, Wang M, Doucet L, 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
7. Zhou C, Heymach JV, et al; WU-KONG28 Investigators. First-line sunvozertinib in NSCLC with EGFR exon 20 insertion mutations. N Engl J Med. Published online May 29, 2026. doi:10.1056/NEJMoa2604461
8. 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
9. Kahl KL. Zipalertinib promising for heavily pretreated EGFR exon 20-mutated lung cancer. Oncology Nursing News. September 17, 2024. Accessed October 22, 2026. https://www.oncnursingnews.com/view/zipalertinib-promising-for-heavily-pretreated-egfr-exon-20-mutated-lung-cancer