Sunvozertinib is an oral targeted therapeutic agent for specific gene mutations, whose active ingredient inhibits the abnormal activity of two proteins, EGFR and HER2. Acting as a precise "genetic key", this medication exerts its effect by targeting specific gene mutations in lung cancer cells.
Indications
1. Diseases Treated
This product exhibits activity against a variety of EGFR genetic abnormalities, primarily targeting the following mutation types:
EGFR exon 20 insertion mutations (a rare type of gene mutation in lung cancer);
T790M resistance mutations (genetic changes that render certain lung cancer drugs ineffective);
EGFR sensitive mutations (the most common driver gene mutations in lung cancer);
EGFR wild-type (the normal unmutated genetic form);
HER2 exon 20 insertion mutations (another genetic abnormality that may trigger cancer).
2. Patient Population and Symptom Relief
This product is specifically indicated for adult patients with advanced lung cancer in the following circumstances:
Patients who have received prior treatment (e.g., platinum-based chemotherapy regimens such as cisplatin and carboplatin) but experienced treatment failure (including tumor progression during/after chemotherapy or intolerance to chemotherapy side effects).
Adult patients with genetically confirmed EGFR exon 20 insertion mutations and a diagnosis of locally advanced or metastatic non-small cell lung cancer (NSCLC), which accounts for approximately 80% of all lung cancer cases.
Important Note: This product has been conditionally approved based on the tumor shrinkage rate and duration of response observed in key clinical trials. Its full approval is subject to the results of large-scale controlled clinical trials.
Dosage and Administration
1. Dosage Form and Strength
Tablets: Available in two strengths, 150 mg and 200 mg, with the corresponding dosage marked on the surface of each tablet.
2. Recommended Administration
Standard Dosage: 300 mg once daily (equivalent to two 150 mg tablets), to be continued until disease progression or the occurrence of unacceptable adverse reactions.
Administration Route: Oral administration. It is recommended to take the medication at the same fixed time each day (e.g., after breakfast or dinner), either on an empty stomach or with food. Administration with food is preferred to reduce gastrointestinal discomfort. Swallow the tablets whole with plain water; do not crush, split or chew the tablets.
3. Dosage Modifications
For Adverse Reactions
If adverse reactions occur, treatment interruption or dosage reduction may be required. The initial dosage reduction is to 200 mg once daily (one 200 mg tablet or two 100 mg tablets); a further reduction to 150 mg once daily is indicated if additional dosage adjustment is needed.
For Concomitant Medications:
Concomitant use with potent CYP3A inhibitors (enzymes that affect drug metabolism) should be avoided. If coadministration is unavoidable, reduce the dosage to 200 mg once daily and resume the original standard dosage after discontinuation of the CYP3A inhibitor.
For Hepatic Impairment
No dosage adjustment is required for mild hepatic impairment (total bilirubin ≤ upper limit of normal [ULN] with elevated aspartate aminotransferase [AST], or total bilirubin > ULN but ≤ 1.5×ULN). The safety and efficacy of this product in patients with moderate to severe hepatic impairment (total bilirubin > 1.5×ULN to 3×ULN or > 3×ULN) have not been established; use with caution.
For Renal Impairment
No dosage adjustment is required for mild to moderate renal impairment (creatinine clearance ≥ 30 mL/min). The safety and efficacy of this product in patients with severe renal impairment (creatinine clearance < 30 mL/min or requiring dialysis) have not been established; use with caution.
Contraindications
Patients with a known hypersensitivity to Sunvozertinib or any of the excipients in the formulation.
Adverse Reactions
Nausea, diarrhea, vomiting and elevated creatine phosphokinase (CPK) occurred in more than 20% of treated patients. Approximately 10% of patients experienced serious adverse reactions, among whom 3.7% developed interstitial lung disease (ILD)/non-infectious pneumonitis.
Detailed Information on Key Adverse Reactions
ILD/non-infectious pneumonitis
Occurred in 4.3% of patients, with 2.7% experiencing Grade ≥3 events. The median onset was approximately 70 days after treatment initiation; treatment interruption or permanent discontinuation may be required for some patients.
QT interval prolongation (ECG)
Occurred in 4.3% of patients, with 2% experiencing severe events. The median onset was approximately 12 days after treatment initiation; most cases improved with treatment interruption or dosage adjustment.
Diarrhea
Occurred in approximately two-thirds of patients, with 9.3% experiencing severe events. The median onset was on the 9th day of treatment; most cases were relieved with symptomatic treatment.
Elevated CPK
Occurred in 4.3% of patients, with 12% experiencing severe events. Most cases resolved with dosage modification, and no rhabdomyolysis was reported. Close monitoring is required; patients should promptly report muscle pain or weakness to their physician.
Main Causes of Treatment Interruption/Dosage Reduction
Approximately one-third of patients required treatment interruption, mainly due to diarrhea (8%), elevated CPK (6.3%) and rash (4%).
Approximately one-fifth of patients required dosage reduction, mainly due to elevated CPK (5%) and diarrhea (4.3%).
Approximately 5.3% of patients discontinued treatment permanently, mainly due to pulmonary inflammation (4%) and diarrhea (4.3%).
Precautions
Pre-Treatment Considerations
This product is contraindicated in pregnant women. Lactating women, patients operating motor vehicles or machinery, and patients with hepatic/renal impairment should use this product with caution, and only under close medical supervision if necessary.
Before treatment, inform the physician of all concomitant medications, pre-existing medical conditions and planned pregnancy. Lactating patients should also disclose their breastfeeding status to the physician.
Special Populations Requiring Caution
Driving and Operating Machinery
Fatigue may occur after administration. Patients are advised to exercise caution when driving or operating machinery during treatment and to discontinue such activities if fatigue develops.
Hepatic Impairment
The safety and efficacy in patients with moderate to severe hepatic impairment have not been established; use with caution.
Renal Impairment
The safety and efficacy in patients with severe renal impairment have not been established; use with caution.
Post-Treatment Considerations
Adhere strictly to the physician’s instructions during treatment, monitor closely for adverse reactions, maintain a light diet and avoid spicy and irritating foods (e.g., chili, Chinese prickly ash) to prevent reduced efficacy or exacerbated discomfort.
Discontinue use immediately if abnormal changes in the color, shape or odor of the medication are observed.
Store the medication in a sealed container below 30℃ in a dry place, and keep it out of the reach of children.
Management of Missed Dose and Overdosage
Missed Dose: If a dose is missed and discovered within 4 hours of the scheduled time, take the missed dose immediately. If more than 4 hours have passed, skip the missed dose and resume the regular dosing schedule at the next scheduled time. Do not take a double dose to make up for a missed one.
Overdosage: In case of overdosage, contact a physician immediately or seek medical attention at a hospital. Closely monitor for changes in physical condition and initiate symptomatic treatment promptly for any discomfort (e.g., dizziness, nausea).
Discontinuation Criteria
Discontinue the drug immediately and seek medical attention if any of the following conditions occur:
Development of ILD/non-infectious pneumonitis (e.g., dyspnea, cough, fever);
Development of QT interval prolongation with arrhythmia-related symptoms (e.g., palpitations, dizziness);
Severe muscle injury (e.g., muscle pain, weakness with significantly elevated CPK);
Severe hepatic impairment (e.g., jaundice, fatigue, anorexia);
Severe hypersensitivity reaction (e.g., rash, pruritus, dyspnea).
Use in Special Populations
Pregnancy
Animal studies have shown that this product may cause miscarriage and fetal developmental abnormalities. Avoid use during pregnancy unless absolutely necessary.
Lactation
It is unknown whether Sunvozertinib is excreted in human milk. Discontinue breastfeeding during treatment with this product.
Pediatric Patients
The safety and efficacy of this product in patients under 18 years of age have not been established.
Geriatric Patients
Clinical trial data showed no significant differences in efficacy and adverse reaction profiles between patients aged ≥65 years and younger patients when receiving the standard dosage (300 mg once daily).
Patients Planning Pregnancy or Lactating
Proactively inform the physician of pregnancy or breastfeeding plans for a comprehensive evaluation of the treatment regimen.
Drug Interactions
1. Interactions with CYP3A Inhibitors/Inducers
Potent CYP3A inhibitors (e.g., clarithromycin, itraconazole): May increase the plasma concentration of Sunvozertinib. Avoid concomitant use; if coadministration is unavoidable, dosage adjustment is required.
Moderate CYP3A inhibitors: Have minimal impact on the efficacy of Sunvozertinib; no dosage adjustment is generally required.
CYP3A inducers (e.g., rifampicin, phenytoin): May reduce the efficacy of Sunvozertinib. Avoid concomitant use.
2. Interactions with Specific Drugs
Concomitant use with specific drugs (e.g., digoxin, methotrexate) may affect the metabolism of these drugs. Close monitoring for adverse reactions is required during coadministration.
Important Note: Sunvozertinib is metabolized to DZ0753 in the human body, a metabolite with anticancer activity similar to the parent drug. However, research on the drug-drug interactions of this metabolite is insufficient, and coadministration with other drugs may affect therapeutic efficacy or increase the risk of adverse reactions. The specific medication regimen must be strictly followed as directed by a physician; do not adjust the dosage without professional medical advice.
