Sunvozertinib (Zegfrovy) Tablets
September 15, 2025 4 minutes read
By William Elliott, MD, FACP, and James Chan, PharmD, PhD
The U.S. Food and Drug Administration (FDA) has granted an accelerated approval to sunvozertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for the treatment of non-small cell lung cancer with epidermal growth factor receptor (EGFR) exon 20 insertion mutations (EGFR exon20ins). The FDA also approved a companion diagnostic device, Oncomine Dx Express Test to help detect exon20ins mutations. Sunvozertinib was granted a priority review and a breakthrough therapy designation.1 It was developed as a joint venture company formed by AstraZeneca and the Chinese Future Industry Investment Fund and distributed by Dizal (Jiagsu) Pharmaceuticals Co., Ltd., as Zegfrovy.
Indications
Sunvozertinib is indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer with EGFR exon20ins, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.2 It was granted accelerated approval based on overall tumor response and duration of response. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.2
Dosage
The recommended dosage is 200 mg orally once daily with food.2 Dosage should be modified for type and severity of adverse reactions and concomitant administration of strong cytochrome P450, family 3, subfamily A (CYP3A) inhibitors and strong and moderate CYP3A inducers.2 The dosage continues until disease progression or unacceptable toxicity occurs. Sunvozertinib is available as 200-mg and 150-mg tablets.
Potential Advantages
Sunvozertinib has potent activity against EGFR exon20ins, EGFR T790M resistance, EGFR sensitizing mutations, and EGFR uncommon mutations with weak activity against wild-type EGFR.3,4 There currently is no effective targeted therapy for EGFR exon20ins mutations in non-small cell lung cancer.
Potential Disadvantages
Adverse reactions that necessitate discontinuation of sunvozetinib include interstitial lung disease, ocular toxicity (ulcerative keratitis), grade 4 dermatologic reactions, and recurrent grade 4 diarrhea.2 Sunvozetinib can cause fetal harm. Appropriate nonhormonal contraception for female patients and effective contraception for male partners should be used during and for two weeks after the last dose.2 Sunvozertinib is a substrate of CYP3A. Therefore, strong CYP3A inhibitors and strong and moderate CYP3A inducers should be avoided. Hormonal contraceptives also should be avoided. Sunvozertinib is an inhibitor of P-glycoprotein and breast cancer resistance protein, so it may increase the risks of adverse reactions to substrates of these transporters. Frequent (> 40%) adverse reactions include diarrhea (73%); rash (60%); decreased appetite (52%); fatigue (41%); increases in creatinine (62%), creatine kinase (57%), lipase (47%), and aspartate aminotransferase (44%); and decreases in hemoglobin (61%), lymphocytes (54%), and neutrophils (41%).2
Comments
EGFR exon20ins is mutation where extra deoxyribonucleic acid is inserted into the exon 20 region of the EGFR gene. This can lead to uncontrolled cell growth as well as resistance to EGFR tyrosine inhibitors. Sunvozertinib shows anti-tumor activity against xenograft models of non-small cell lung cancer with EGFR exon20ins.2 The efficacy was evaluated in an open-label, dose randomization trial (WU-KONG 1B) in study participants with locally advanced or metastatic non-small cell lung cancer with EGFR exon20ins with disease progression on or after platinum-based chemotherapy. The major efficacy outcome measure was overall response rate (ORR), according to Response Evaluation Criteria in Solid Tumors (RECIST v 1.1) as evaluated by a blinded independent review committee (BIRC), as well as duration of response (DOR). The efficacy population (n = 85) had a median age of 61 years, 67% were female, 65% were Asian, 71% had never smoked, 96% had metastatic disease, and 25% had brain metastasis. All received prior platinum-based chemotherapy, 42% had prior anti-programmed cell death ligand 1 (PDL-1) therapy, and 14% had received prior amivantamab. The ORR was 46%; 95% confidence interval (CI), 35% to 57%, of which 40% was a partial response. The median response (DOR) was 11.1 months, with 72% achieving DOR ≥ 6 months.
Clinical Implications
EGFR exon20ins accounts for 4% to 10% of EGFR mutations.3 The first-line treatment for newly diagnosed advanced or metastatic EGFR exon20ins mutation non-small cell lung cancer is amivantamab combined with carboplatin and pemetrexed.5 This combination showed an ORR of 67%; 95% CI, 59% to 75%; progression-free survival of 11.4 months, and a hazard ratio of 0.40; 95% CI,0.30-0.53, compared to carboplatin and pemetrexed.5,6 Amivantamab also is approved as a single agent for the treatment of locally advanced or metastatic non-small cell lung cancer with EGFR exon20ins mutation in patients who have progressed on or after platinum-based chemotherapy.5 Sunvozertinib is a new treatment option, but its role will be contingent on confirmation of clinical benefit, particularly with prior amivantanab-treated patients. Numerous trials at various phases are in progress.3 The cost for sunvozertinib was not yet available.
William T. Elliott, MD, FACP, is Assistant Clinical Professor of Medicine, University of California, San Francisco.
James Chan, PharmD, PhD, is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
References
- U.S. Food and Drug Administration. FDA grants accelerated approval to sunvozertinib for metastatic non-small cell lung cancer with EGFR exon 20 insertion mutations. July 2, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sunvozertinib-metastatic-non-small-cell-lung-cancer-egfr-exon-20
- Dizal (Jiangsu) Pharmaceuticals Co., Ltd. Zegfrovy prescribing information. Revised July 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/219839s000lbl.pdf
- Dhillon S. Sunvozertinib: First approval. Drugs. 2023;83(17):1629-1634.
- Wang M, Yang JC-H, Mitchael PL, et al. Sunvozertinib, a selective EGFR inhibitor for previously treated non-small cell lung cancer with EGFR exon 20 insertion mutations. Cancer Discov. 2022;12(7):1676-1689.
- Janssen Biotech Inc. Rybrevant prescribing information. Revised February 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761210s007lbl.pdf
- Zhou C, Tang K-J, Cho BC, et al. Amivantamab plus chemotherapy in NSCLC with EGFR exon 20 insertions. N Engl J Med. 2023;389(22):2039-2051.
The U.S. Food and Drug Administration (FDA) has granted an accelerated approval to sunvozertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for the treatment of non-small cell lung cancer with epidermal growth factor receptor (EGFR) exon 20 insertion mutations (EGFR exon20ins). The FDA also approved a companion diagnostic device, Oncomine Dx Express Test to help detect exon20ins mutations.
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