Sunvozertinib, an irreversible inhibitor of receptor tyrosine kinase, is an antineoplastic agent.1
Sunvozertinib is used for the treatment of adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, detected by an FDA-approved test, after progression on or following platinum-based chemotherapy.1, 2 Information on FDA-approved companion diagnostic tests for the detection of EGFR mutations in NSCLC is available at ([Web]).1 Sunvozertinib was approved under the FDA's accelerated pathway based on response rate and duration of response; continued approval is contingent upon confirmation of clinical benefit in ongoing trials.1, 2
The efficacy of sunvozertinib was evaluated in adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations whose disease progressed on or after platinum-based chemotherapy.1, 2, 3 A multinational, open-label, dose-randomization study enrolled patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 including patients with previously treated and stable intracranial metastases.1, 2, 3 Patients with measurable disease at baseline were randomized to receive oral sunvozertinib 200 mg once daily with food or an unapproved dosage until disease progression or intolerable toxicity.1, 2, 3
The major efficacy endpoint was overall response rate (ORR), assessed by a blinded independent review committee (BIRC) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1).1, 2 Duration of response (DOR) was a key secondary endpoint.1, 2 Among the 85 patients who received sunvozertinib 200 mg once daily, the median was 61 years of age (range, 35-88 years); 67% were female, 65% Asian, and 33% White.1, 2 Most patients had adenocarcinoma histology (94%), metastatic disease (96%), and an ECOG performance status of 1 (61%); 25% had brain metastases.1, 2 Prior therapy included platinum-based chemotherapy (100%), anti-programmed cell death ligand 1 (PD-L1) therapy (42%), and amivantamab (14%).1
All patients were enrolled based on the presence of an EGFR exon 20 insertion mutation confirmed by local or central laboratory testing.1, 2 Retrospective analysis of tumor samples using the Oncomine Dx Express Test confirmed EGFR exon 20 insertions in 68% (58/85) of patients, while 29% (25/85) produced nonreportable results and 2% (2/85) did not have an EGFR exon 20 insertion identified.1, 2
The ORR was 46%, including 6% with a complete response and 40% with a partial response.1, 2 The median DOR was 11.1 months, with 72% of responders maintaining a response for ≥6 months.1, 2
NSCLC represents about 85% of lung cancer cases, with most patients diagnosed at an advanced, inoperable stage and a 5-year overall survival rate of only 15-17%.2 Oncogenic driver mutations in the EGFR gene occur in a significant proportion of NSCLC cases.2 While exon 19 deletions and L858R substitutions are the most common, EGFR exon 20 insertion mutations are the third most frequent, accounting for about 12% of EGFR-mutated NSCLC.2 These molecularly diverse variants (over 100 identified) are typically associated with intrinsic resistance to earlier-generation EGFR tyrosine kinase inhibitors.2
The American Society of Clinical Oncology (ASCO) publishes a guideline addressing the treatment of stage IV NSCLC harboring driver alterations such as EGFR mutations.4 For NSCLC tumors with EGFR exon 20 insertion mutations, amivantamab is the recommended targeted therapy after progression on platinum-based chemotherapy.4 Sunvozertinib has not yet been incorporated into current ASCO guidance.4
Administer sunvozertinib orally with food.1
Swallow tablets whole without splitting, crushing, chewing, or dissolving, and take at the same time each day.1
If a dose of sunvozertinib is missed and <12 hours have passed, take the missed dose as soon as possible.1 If >12 hours have passed, skip the missed dose and take the next dose at the regular time.1 If vomiting occurs after a dose, do not take an extra dose; take the next dose as scheduled.1
Store the tablets at room temperature between 20-25°C.1
The recommended adult dosage of sunvozertinib for the treatment of NSCLC with EGFR exon 20 mutations is 200 mg orally once daily.1
Continue therapy until disease progression or unacceptable toxicity.1
Dosage Modifications for Adverse Reactions
Reduce the sunvozertinib dosage to 150 mg orally once daily with food for the management of adverse reactions.1 Permanently discontinue if the patient cannot tolerate the lower dosage.1
See Table 1 for recommended dosage adjustments.
Adverse Reaction | Severity | Modification |
|---|---|---|
ILD/Pneumonitis | Any Grade | Suspected ILD/pneumonitis: Withhold sunvozertinib. Confirmed ILD/pneumonitis: Permanently discontinue. |
Nausea or Vomiting | Grade 1 | Administer supportive care including antiemetics. |
Nausea or Vomiting | Grade 2 | Administer supportive care, including antiemetics. Withhold sunvozertinib until recovery to Grade ≤1, then resume at the same dosage. |
Nausea or Vomiting | Grade 3 or 4 | Administer supportive care, including antiemetics. Withhold sunvozertinib until recovery to Grade ≤1, then resume at the next lower dosage. |
Diarrhea | Grade 1 | Administer supportive care including anti-diarrheals (i.e., loperamide). |
Diarrhea | Grade 2 or 3 | First occurrence: Withhold sunvozertinib and administer supportive care, including anti-diarrheals (i.e., loperamide). Resume sunvozertinib at the same dosage once diarrhea has recovered to Grade ≤1. Recurrence: Withhold sunvozertinib until recovery to Grade ≤1; then resume sunvozertinib at the next lower dosage. |
Diarrhea | Grade 4 | First occurrence: Withhold sunvozertinib and provide supportive care, including anti-diarrheals (i.e., loperamide). If diarrhea resolves to Grade ≤1 within 3 weeks, resume sunvozertinib at the next lower dosage. If not resolved within 3 weeks, permanently discontinue sunvozertinib. Recurrence: Permanently discontinue sunvozertinib. |
Dermatologic Adverse Reactions | Grade 2 | Administer supportive care; reassess within 3 weeks, if rash does not improve, consider dosage reduction. |
Dermatologic Adverse Reactions | Grade 3 | Withhold sunvozertinib and administer supportive care. Upon recovery to Grade ≤1, resume sunvozertinib at the next lower dosage. If no improvement within 3 weeks, permanently discontinue sunvozertinib. |
Dermatologic Adverse Reactions | Grade 4 | Permanently discontinue sunvozertinib. |
Ocular Toxicity | Any Grade | Suspected ulcerative keratitis: Withhold sunvozertinib. Confirmed ulcerative keratitis: Permanently discontinue sunvozertinib. |
Other Adverse Reactions | Grade 3 or 4 | Withhold sunvozertinib. If resolved to Grade ≤1 within 3 weeks, resume sunvozertinib at the same or next lower dosage. If not resolved to Grade ≤1 within 3 weeks, permanently discontinue sunvozertinib. |
Dosage Modifications for Drug Interactions
Avoid concomitant use of strong cytochrome P-450 (CYP) 3A inhibitors.1 If unavoidable, reduce the sunvozertinib dose from 200 mg to 150 mg.1 After discontinuing the inhibitor, resume the prior sunvozertinib dose after 3-5 half-lives of the inhibitor.1
Avoid concomitant use of strong and moderate CYP3A inducers.1 If unavoidable, increase the sunvozertinib dose from 200 mg to 400 mg.1 After discontinuing the inducer, resume the prior sunvozertinib dose 7-14 days later.1
The manufacturer makes no specific dosage recommendations for patients with hepatic impairment.1
The manufacturer makes no specific dosage recommendations for patients with renal impairment.1
The manufacturer makes no specific dosage recommendations for geriatric patients.1
Interstitial Lung Disease (ILD)/Pneumonitis
Sunvozertinib can cause severe, life-threatening ILD/pneumonitis.1 In the safety population, ILD/pneumonitis occurred in 1.7% of patients (median onset 61 days; range 35-86 days), causing 0.8% of patients to discontinue sunvozertinib.1 Monitor for new or worsening dyspnea, cough, or fever.1 Withhold sunvozertinib if ILD/pneumonitis is suspected and permanently discontinue if confirmed.1
Sunvozertinib can cause severe GI adverse reactions, including diarrhea, nausea, and vomiting.1 In the safety population, serious GI events occurred in 1.7% of patients (0.8% with Grade 3 nausea).1 Diarrhea occurred in 73% of patients (2.5% with Grade 3) and led to dosage interruption or reduction in 5% of patients and permanent discontinuation in 0.8% of patients.1 Nausea and vomiting occurred in 43% (3.3% with Grade 3) and led to dosage changes in 7% of patients and discontinuation in 0.8% of patients.1 Administer sunvozertinib with food to minimize GI effects.1 Monitor for toxicity and provide supportive care (e.g., anti-diarrheals, antiemetics, fluids).1 Withhold, reduce, or permanently discontinue based on severity.1
Dermatologic Adverse Reactions
Sunvozertinib can cause severe rash, including acneiform dermatitis and pruritus.1 In the safety population, dermatologic adverse reactions occurred in 68% of patients, including 9% of patients with acneiform dermatitis.1 Grade 3 reactions included rash (7%), acneiform dermatitis (0.8%), and pruritus (0.8%).1 Advise patients to use alcohol-free emollient creams and avoid irritating skin products such as those containing retinol, retinoic acid, or benzoyl peroxide.1 Withhold, reduce, or permanently discontinue sunvozertinib based on severity.1
Sunvozertinib can cause ocular toxicity, including keratitis, dry eyes, blurred vision, and visual impairment.1 In the safety population, ocular toxicity occurred in 13% of patients, including 0.8% of patients with keratitis.1 Promptly refer patients with new or worsening eye symptoms to an ophthalmologist and advise patients to discontinue use of contact lenses until symptoms are evaluated.1 Withhold, reduce, or permanently discontinue sunvozertinib based on severity.1
Fetal/Neonatal Morbidity and Mortality
Based on animal studies and its mechanism of action, sunvozertinib can cause fetal harm when administered during pregnancy.1 In animals, oral sunvozertinib during organogenesis caused structural abnormalities at exposures below those observed in humans at the recommended dosage.1 Advise pregnant women and females of reproductive potential of the potential fetal risk.1 Females of reproductive potential should use effective non-hormonal contraception during treatment and for 2 weeks after the last dosage, as sunvozertinib may reduce hormonal contraceptive effectiveness.1 Male patients with female partners of reproductive potential should also use effective contraception during treatment and for 2 weeks after the final dose.1
Based on animal data and its mechanism of action, sunvozertinib can cause fetal harm if used during pregnancy.1 No human pregnancy data are available to inform a drug-associated risk.1 In animals, oral sunvozertinib during organogenesis caused structural abnormalities at exposures below those seen in humans at the recommended dosage.1 Advise pregnant women and females of reproductive potential of the potential fetal risk.1
It is not known whether sunvozertinib is distributed into human milk or has any effects on the breastfed infant or on milk production.1 Due to the potential for serious adverse reactions, advise women not to breastfeed during treatment and for 2 weeks after the last dose.1
Females and Males of Reproductive Potential
Based on animal data and its mechanism of action, sunvozertinib can cause fetal harm when administered during pregnancy.1 Verify the pregnancy status of females of reproductive potential before starting treatment.1 Advise females to use effective non-hormonal contraception during therapy and for 2 weeks after the last dosage, as sunvozertinib may decrease the effectiveness of hormonal contraceptives.1 Male patients with female partners of reproductive potential should also use effective contraception during treatment and for 2 weeks after the final dosage.1 Based on animal studies, sunvozertinib may impair fertility in both males and females; effects in males were reversible, while reversibility in females was not assessed.1
The safety and effectiveness of sunvozertinib in pediatric patients have not been established.1
Of the 121 patients who received sunvozertinib 200 mg in clinical studies, 43% were ≥65 years of age and 9% were ≥75 years of age.1 Effectiveness was similar between patients ≥65 years of age and those younger.1 However, patients ≥65 years of age experienced a higher incidence of Grade ≥3 adverse reactions (69% vs 52%) and serious adverse reactions (48% versus 38%) compared with younger patients.1
The most common (≥20%) adverse reactions reported with sunvozertinib in clinical studies were diarrhea, rash, decreased appetite, stomatitis, fatigue, nausea, paronychia, vomiting, constipation, musculoskeletal pain, pruritus, dry skin, urinary tract infection, abdominal pain, and decreased weight.1
The most common (≥2%) Grade 3 or 4 laboratory abnormalities reported with sunvozertinib in clinical studies were decreased lymphocytes, increased lipase, decreased hemoglobin, increased amylase, increased creatine kinase, decreased neutrophils, decreased potassium, increased aspartate aminotransferase, increased alanine aminotransferase, decreased sodium, increased magnesium, and increased alkaline phosphatase.1
Sunvozertinib is metabolized principally by cytochrome P-450 (CYP) isoenzyme 3A and is both a CYP3A substrate and inducer.1
Sunvozertinib inhibits breast cancer resistance protein (BCRP) and organic anion transporting polypeptide (OATP) 1B1 and is both an inhibitor and substrate for P-glycoprotein (P-gp).1
Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes
Avoid concomitant use of sunvozertinib with strong CYP3A inhibitors.1 Itraconazole increased sunvozertinib exposure by 30-50%.1 If use cannot be avoided, reduce the dosage as recommended and monitor for increased adverse effects of sunvozertinib.1
Avoid concomitant use with strong and moderate CYP3A inducers.1 Coadministration of sunvozertinib with strong CYP3A inducers decreases sunvozertinib exposure, which may reduce efficacy.1 Coadministration with carbamazepine decreased sunvozertinib exposure by 38-48% and efavirenz is predicted to decrease sunvozertinib exposure by approximately 44%.1 If coadministration cannot be avoided, increase the sunvozertinib dosage as directed.1
Avoid concomitant use of sunvozertinib with hormonal contraceptives that are CYP3A substrates.1 Sunvozertinib induces CYP3A4; decreased exposure of a sensitive CYP3A substrate (midazolam) by 15-23% was reported with concomitant use of sunvozertinib, indicating that the drug may lower plasma concentrations of hormonal contraceptives and reduce their effectiveness.1 Advise females of reproductive potential to use effective non-hormonal contraception during treatment and for 2 weeks after the last dosage.1
Drugs Affecting or Affected by Transport Systems
Digoxin (P-gp substrate) exposure increased by 20-40% and rosuvastatin (BCRP substrate) exposure increased by 40-60% when administered concomitantly with sunvozertinib.1 Monitor for increased adverse effects of P-gp or BCRP substrates when coadministered with sunvozertinib.1
Sunvozertinib, an antineoplastic agent, is an oral kinase inhibitor that binds to and inhibits epidermal growth factor receptor (EGFR) exon 20 insertion mutations.1, 2 In laboratory studies, sunvozertinib blocked EGFR activity in cells with exon 20 insertion mutations at concentrations 2-10 times lower than those required to affect wild-type (non-mutant) EGFR.1
Sunvozertinib demonstrates dose-proportional increases in peak plasma concentrations and AUC over the dosage range of 50 to 400 mg (0.25 to 2 times the approved dose).1 At the approved dosage, sunvozertinib reaches steady-state within 15 days, with overall drug exposure (i.e., AUC) increasing 3-fold.1 The median time to reach peak plasma concentration is about 6 hours (range, 3 to 10 hours).1 Administration with a high-fat meal (about 1,000 calories; 50% fat) does not result in clinically significant differences in exposure.1 Plasma protein binding ranges from 89-94% in vitro.1 The elimination half-life of sunvozertinib is approximately 50 hours.1 Sunvozertinib is primarily metabolized by cytochrome P-450 (CYP) 3A, producing an active demethylated metabolite, DZ0753, which accounts for about 10% of the total systemic exposure of the parent compound.1 Following a single oral dose of radiolabeled sunvozertinib, 79% of the administered dose is recovered in feces (7.3% unchanged) and 10% in urine (5.6% unchanged).1
No clinically meaningful differences in the pharmacokinetics of sunvozertinib have been observed across age (19-96 years of age), sex, race (Asian 62%, White 28%, Black 8%), body weight (30-118 kg), smoking status, or in patients with mild to moderate renal impairment (creatinine clearance [Clcr] 30-89 mL/minute), or mild to moderate hepatic impairment.1 The pharmacokinetics of sunvozertinib have not been studied in patients with severe hepatic impairment (total bilirubin >3 times upper limit of normal) or severe renal impairment (Clcr 15-29 mL/minute).1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets, film-coated | 150 mg | Zegfrovy® | Dizal (Jiangsu) Pharmaceutical |
200 mg | Zegfrovy® | Dizal (Jiangsu) Pharmaceutical |
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions January 10, 2026. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
1. Dizal (Jiangsu) Pharmaceutical Co., Ltd. ZEGFROVY (sunvozertinib) ORAL prescribing information. 2025 Jul.
2. Food and Drug Administration. Center for Drug Evaluation and Research. Application number 219839Orig1s000: Multidiscipline review.[Web] [Web]
3. 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.
4. Joshua E. Reuss et al. Therapy for stage IV non-small cell lung cancer with driver alterations: ASCO living guideline, Version 2025.1. J Clin Oncol 43, e31-e44(2025) [Web]