Sunvozertinib (Monograph)

Brand name: Zegfrovy
Drug class: Antineoplastic Agents

Introduction

Sunvozertinib is a kinase inhibitor of the epidermal growth factor receptor (EGFR).

Uses for Sunvozertinib

Sunvozertinib has the following uses:

Sunvozertinib is indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.

Sunvozertinib Dosage and Administration

General

Sunvozertinib is available in the following dosage form(s) and strength(s):

Tablets: 150 mg and 200 mg

Dosage

Adults

Dosage and Administration

• Select patients for treatment with sunvozertinib for locally advanced or metastatic NSCLC based on the presence of EGFR exon 20 insertion mutations in tumor tissue.

• The recommended dosage of sunvozertinib is 200 mg orally once daily with food until disease progression or unacceptable toxicity. Swallow sunvozertinib tablets whole. Do not split, crush, chew, or dissolve the tablets. Take sunvozertinib at the same time each day.

• See Full Prescribing Information for dosage modification recommendations for adverse reactions and for concomitant use with cytochrome P-450 (CYP) 3A inhibitors or inducers.

Cautions for Sunvozertinib

Contraindications

• None.

Warnings/Precautions

Interstitial Lung Disease/Pneumonitis

Sunvozertinib can cause severe and life-threatening interstitial lung disease (ILD)/pneumonitis. In the safety population, ILD/pneumonitis occurred in 1.7% of patients. The median time to first onset for ILD/pneumonitis was 61 days (range: 35 to 86 days). Sunvozertinib was discontinued due to ILD/pneumonitis in 0.8% of patients.

Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, and fever). Immediately withhold sunvozertinib in patients with suspected ILD/pneumonitis and permanently discontinue the drug if ILD/pneumonitis is confirmed.

Gastrointestinal Adverse Reactions

Sunvozertinib can cause severe GI adverse reactions including diarrhea, nausea, and vomiting. In the safety population, serious GI adverse reactions occurred in 1.7% of patients, including 0.8% Grade 3 nausea. Diarrhea occurred in 73% of patients who received sunvozertinib, including 2.5% Grade 3. Diarrhea leading to dosage interruption or dose reduction occurred in 5% of patients and required permanent discontinuation of the drug in 0.8% of patients. Nausea and vomiting occurred in 43% of patients, including 3.3% Grade 3 events. Nausea and vomiting leading to dosage interruption or dose reduction occurred in 7% of patients and permanent discontinuation of therapy in 0.8% of patients. Administer sunvozertinib with food to reduce GI adverse reactions. Monitor patients for GI toxicity, and provide supportive care, including anti-diarrheals, anti-emetics, or fluid replacement, as indicated. Withhold, reduce the dose, or permanently discontinue sunvozertinib based on severity.

Dermatologic Adverse Reactions

Sunvozertinib can cause severe rash including acneiform dermatitis and pruritus. Based on the safety population, dermatologic adverse reactions occurred in 68% of patients including 9% acneiform dermatitis. Grade 3 dermatologic adverse reactions were 7% rash, 0.8% acneiform dermatitis, and 0.8% pruritus. Instruct patients to use alcohol-free (e.g., isopropanol-free, ethanol-free) emollient cream during treatment with sunvozertinib and to avoid the use of irritating skin products (e.g., products containing retinol or retinoic acid, benzoyl peroxides). Withhold, reduce the dose, or permanently discontinue sunvozertinib based on severity.

Ocular Toxicity

Sunvozertinib can cause ocular toxicity including keratitis, dry eye symptoms, blurred vision, and visual impairment. Based on the safety population, ocular toxicity occurred in 13% of patients who received sunvozertinib, including keratitis (0.8%). Promptly refer patients with new or worsening eye symptoms to an ophthalmologist. Advise discontinuation of contact lenses until ocular symptoms are evaluated. Withhold, reduce the dose, or permanently discontinue sunvozertinib based on severity.

Embryo-Fetal Toxicity

Based on findings from animal studies and its mechanism of action, sunvozertinib can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, oral administration of sunvozertinib to pregnant animals during the period of organogenesis resulted in structural abnormalities at concentrations below the human exposure at the recommended dose based on AUC.

Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with sunvozertinib and for 2 weeks after the last dose, since sunvozertinib can render some hormonal contraceptives ineffective. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with sunvozertinib and for 2 weeks after the last dose.

Specific Populations

Pregnancy

Based on findings from animal studies and its mechanism of action, sunvozertinib can cause fetal harm when administered to a pregnant woman. There are no available data on the use of sunvozertinib in pregnant women to inform a drug-associated risk. Oral administration of sunvozertinib to pregnant animals during the period of organogenesis resulted in structural abnormalities at concentrations below the human exposure at the recommended dose based on AUC. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Lactation

There are no data on the presence of sunvozertinib or its metabolites in human milk or their effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with sunvozertinib and for 2 weeks after the last dose.

Females and Males of Reproductive Potential

Based on animal data and mechanism of action, sunvozertinib can cause fetal harm when administered to pregnant women. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with sunvozertinib and for 2 weeks after the last dose. Sunvozertinib may render hormonal contraceptives ineffective. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with sunvozertinib and for 2 weeks after the last dose. Based on animal studies, sunvozertinib may impair fertility in females. The reversibility of the effects on female fertility was not assessed. Based on animal studies, sunvozertinib may impair fertility in males. The effects on male fertility were reversible.

Pediatric Use

The safety and effectiveness of sunvozertinib in pediatric patients have not been established.

Geriatric Use

Of the 121 patients who received sunvozertinib 200 mg in clinical studies, 43% were 65 years of age and over, and 9% were 75 years of age and over. No overall difference in effectiveness was observed between patients who were ≥65 years of age and younger patients. There was a higher incidence of adverse reactions of Grade ≥3 (69% versus 52%) and serious adverse reactions (48% versus 38%) in patients at 65 years of age and older as compared to those younger than 65 years.

Common Adverse Effects

The most common (≥20%) adverse reactions 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 (≥2%) Grade 3 or 4 laboratory abnormalities 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.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

• Strong CYP3A Inhibitors: Avoid concomitant use. If concomitant use cannot be avoided, reduce sunvozertinib dose.

• Strong and Moderate CYP3A Inducers: Avoid concomitant use. If concomitant use cannot be avoided, increase sunvozertinib dose.

• P-gp or BCRP Substrates: Monitor for increased adverse reactions during concomitant use with sunvozertinib.

• Hormonal Contraceptives: Avoid concomitant use.

Actions

Mechanism of Action

Sunvozertinib is a kinase inhibitor of the epidermal growth factor receptor (EGFR) that binds to and inhibits EGFR exon 20 insertion mutations at similar concentrations as wild-type EGFR. In cultured cell models, sunvozertinib inhibited EGFR phosphorylation in cells expressing different EGFR exon 20 insertion mutation variants at approximately 2- to 10-fold lower concentrations than wild-type EGFR signaling inhibition. Sunvozertinib exhibited anti-tumor activity against xenograft models of NSCLC with EGFR exon 20 insertion mutations.

Advice to Patients

• Advise the patient to read the FDA-approved patient labeling (Patient Information).

• Advise patients that sunvozertinib can cause interstitial lung disease/pneumonitis. Advise patients to immediately contact their healthcare provider for new or worsening respiratory symptoms.

• Advise patients that sunvozertinib can cause GI toxicity, including nausea, vomiting, and diarrhea. Advise patients to take sunvozertinib with food to reduce GI adverse reactions. Advise patients to immediately contact their healthcare provider for symptoms of GI toxicity.

• Advise patients that sunvozertinib can cause dermatologic adverse reactions, including rash and pruritus. Advise patients to use alcohol-free (e.g., isopropanol-free, ethanol-free) emollient cream during treatment with sunvozertinib and to avoid the use of irritating skin products (e.g., products containing retinol or retinoic acid, benzoyl peroxides). Advise patients to immediately contact their healthcare provider for symptoms of dermatologic adverse reactions.

• Advise patients that sunvozertinib can cause ocular toxicity. Advise patients to contact their healthcare provider if they develop eye symptoms. Advise discontinuation of contact lenses until symptoms are evaluated and at least one week after symptoms have resolved.

• Advise females of reproductive potential of the potential risk to a fetus and to inform their healthcare provider of a known or suspected pregnancy. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with sunvozertinib and for 2 weeks after the last dose, since sunvozertinib can render some hormonal contraceptives ineffective. Advise males with female partners of reproductive potential to use effective contraception during treatment with sunvozertinib and for 2 weeks after the last dose.

• Advise women not to breastfeed during treatment with sunvozertinib and for 2 weeks after the last dose.

• Advise females and males of reproductive potential that sunvozertinib may impair fertility.

• Advise patients to inform their healthcare providers of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, and herbal products.

Additional Information

AHFSfirstRelease™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

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.

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