100mg Entrectinib Immune Drugs 30 Capsules For Pan Tumor Targeted

Drug Name
Generic Name: Entrectinib Capsules

Trade name: Rozhengquan®, English trade name: Rozlytrek®.

English name: Entrectinib Capsules

Hanyu Pinyin: Enqutini Jiaonan

Indications
Solid tumors

This product is suitable for adults and children aged 12 years and above with solid tumors who meet the following conditions.

Diagnosed with a neurotrophic tyrosine receptor kinase (NTRK) fusion gene by a well-validated assay that does not include a known acquired resistance mutation.

Patients with locally advanced, metastatic disease or surgical resection that may result in serious complications, and patients for whom there is no satisfactory alternative therapy or who have failed prior therapy.

This indication was conditionally approved for marketing based on surrogate endpoints, clinical endpoint data are not yet available, and efficacy and safety are subject to further post-market validation.

Non-Small Cell Lung Cancer (NSCLC)

This product is indicated for adult patients with ROS1-positive locally advanced or metastatic non-small cell lung cancer (NSCLC).

[Dosage
Patient Selection

Solid tumor

Treatment with this product should be initiated by a physician experienced in anti-cancer therapy.

Prior to treatment with this product, it must be determined that the patient's tumor sample carries the NTRK fusion gene. A validated assay should be used to determine the patient's NTRK fusion gene status. Patients who have been determined by hospital or laboratory testing to harbor an NTRK fusion gene are eligible for treatment with this product and should have a review by an independent third party, designated by Roche, to confirm that the patient has an NTRK fusion gene and can continue to be treated with this product.

Non-Small Cell Lung Cancer (NSCLC)

A validated assay is required to select patients with ROS1-positive locally advanced or metastatic NSCLC. ROS1-positive status should be determined prior to initiating treatment with entrectinib.

Recommended Dose

This product is indicated for oral administration. Hard capsules should be swallowed whole and should not be opened or dissolved for administration as the contents are bitter. This product may be taken with or without food, but should not be taken with grapefruit or grapefruit juice.

ADULTS: The recommended dose for adults is 600 mg orally once daily.

Pediatric Patients: The recommended dose for pediatric patients 12 years of age and older is 300 mg/m2 orally once daily (see Table 1).

▼ Table 1: Recommended Dosing Regimens for Pediatric Patients

Body Surface Area (BSA) Once-daily dosing
1.11-1.50 m2 400 mg
≥ 1.51m2 600 mg
Duration of treatment

It is recommended that patients receive this product until disease progression, or intolerable toxicity occurs.

Delayed or missed doses

If a patient misses a dose, make up the dose unless the next dose is less than 12 hours away.

If a patient vomits immediately after taking entrectinib, the patient may take another dose.

Dose Adjustments for Adult Patients

The dose of entrectinib may be reduced up to two times in adults, depending on tolerability. Table 2 provides generic dose adjustment recommendations for adult patients. If a patient cannot tolerate a dose of 200 mg once daily, therapy with entrectinib should be permanently discontinued.

▼ Table 2 Dose Reduction Options for Adult Patients

Dose Reduction Program Dose Level
Starting dose 600 mg once daily
First reduction 400 mg once daily
Second reduction 200 mg once daily
Dose Adjustment for Pediatric Patients


Special dosage reduction recommendations for pediatric patients are provided in Table 3. A maximum of two dose reductions may be made in pediatric patients 12 years of age or older, depending on tolerability.

Some pediatric patients require an intermittent dosing regimen to achieve the recommended total weekly dose after reduction. If the patient cannot tolerate the lowest recommended dose after reduction, therapy with emtricitinib should be permanently discontinued.

▼ Table 3 Dose Reduction Regimens for Pediatric Patients

Measure
BSA 1.11-1.50 m2

(once daily)

BSA ≥ 1.51 m2

(once daily)

Recommended Dose
600 mg
First reduction 300 mg 400 mg
Second Reduction 5 days per week* 200 mg 200 mg
*5 days per week: Monday, Wednesday, Friday, Saturday, and Sunday
Dose Adjustments Following Specific Adverse Events


Recommendations for dose adjustments of emtricitinib following specific adverse drug reactions in adult and pediatric patients are shown in Table 4.

▼ Table 3 Recommended Dose Adjustment Regimens After a Drug-Specific Adverse Reaction in Adult and Pediatric Patients

Adverse Drug Reaction Severity* Dose Adjustment
Anemia or neutropenia Grade 3 or 4 Suspend treatment with entrectinib until return to ≤ Grade 2 or baseline and restart treatment at the original dose or at a reduced dose, depending on clinical need.
Cognitive impairment ≥ grade 2
Suspend treatment with emtricitinib until recovery to ≤ grade 1 or baseline, restart treatment at the original dose or at a reduced dose.

If adverse events recur, reduce dose again.

For long-standing, severe or intolerable events, consider discontinuation of treatment based on clinical status.

Grade 3 transaminase elevation
Suspend treatment with entrectinib until recovery to ≤ Grade 1 or baseline.

If recovery occurs within 4 weeks, restart treatment at the original dose.

If the adverse reaction does not recover within 4 weeks, discontinue treatment permanently.

If the recurrent Grade 3 event recovers within 4 weeks, restart treatment at a reduced dose.

Grade 4
Suspend treatment with entrectinib until recovery to ≤ Grade 1 or baseline.

If recovery within 4 weeks, restart treatment after dose reduction.

If adverse reactions do not recover within 4 weeks, discontinue treatment permanently.

If a recurrence of a Grade 4 adverse event occurs, treatment is permanently discontinued.

Elevation of ALT or AST > 3 × ULN; and elevation of total bilirubin > 2 × ULN (without cholestasis or hemolysis) Permanently discontinue treatment with emtricitinib.
Hyperuricemia Symptomatic or grade 4
Initiate uric acid-lowering medications.

Suspend treatment with entrectinib until signs or symptoms improve.

Restart treatment with entrectinib at the original dose or at a reduced dose.

Congestive heart failure grade 2 or 3
Suspend treatment with emtricitinib until recovery to ≤ grade 1.

Restart treatment after dose reduction.

Grade 4
Suspend treatment with entrectinib until recovery to ≤ Grade 1.

Restart therapy after dose reduction or discontinue therapy, depending on clinical status.

QT interval prolongation QTc 481-500 ms
Suspend treatment with entrectinib until return to baseline.

Restart treatment at original dose.

QTc > 500 ms
Suspend treatment with entrectinib until QTc intervals return to baseline.

If the cause of the QT prolongation is identified and corrected, restart treatment at the original dose.

If there are other unspecified causes of QT prolongation, reduce the dose and restart treatment.

Tip-twist ventricular tachycardia; polymorphic ventricular tachycardia; signs/symptoms of severe arrhythmia Permanently discontinue treatment with emtricitinib.
Other clinically significant adverse reactions Grade 3 or 4
Suspend treatment with entrectinib until adverse reactions return or improve to Grade 1 or baseline.

If recovery occurs within 4 weeks, restart treatment at the original dose or at a reduced dose.

If the adverse reaction does not recover within 4 weeks, consider permanent discontinuation of therapy.

If a recurrence of a Grade 4 adverse event occurs, treatment will be permanently discontinued.

ALT = alanine aminotransferase; AST = aspartate aminotransferase; ULN = upper limit of normal; QTc = QT interval corrected for heart rate.

* severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)

CYP3A potent or intermediate-acting inhibitor coadministration

Adults: In adult patients, coadministration with potent or moderate-acting CYP3A inhibitors should be avoided or limited to 14 days. If coadministration cannot be avoided, the dose of emtricitinib should be reduced to 100 mg once daily when coadministered with a potent CYP3A inhibitor or 200 mg once daily when coadministered with an intermediate-acting CYP3A inhibitor. After discontinuation of the co-administered potent or intermediate-acting CYP3A inhibitor, the dose of entrectinib can be restored to the pre-administered dose. CYP3A4 inhibitors with long half-lives may require an elution period.

Pediatric Patients: Coadministration of potent or moderately potent CYP3A inhibitors should be avoided in pediatric patients 12 years of age or older.

CYP3A Inducer Coadministration

CYP3A inducer combination should be avoided in adult and pediatric patients.

Dosage Instructions for Special Populations

Children: The safety and efficacy of entrectinib have not been established in children under 12 years of age.

Geriatric: No dose adjustment of entrectinib is required in patients ≥65 years of age.

Renal Insufficiency: No dose adjustment is required in patients with mild or moderate renal insufficiency. The safety and efficacy of entrectinib have not been studied in patients with severe renal insufficiency. However, due to the negligible renal elimination of entrectinib, no dose adjustment is required in patients with severe renal insufficiency.

Hepatic Insufficiency: No dose adjustment is recommended for patients with mild hepatic insufficiency. The safety and efficacy of entrectinib have not been studied in patients with moderate to severe hepatic insufficiency.

[Adverse Reactions

The most common adverse reactions (≥20%) were fatigue, constipation, dysgeusia, edema, dizziness, diarrhea, nausea, hypersalivation, dyspnea, anemia, weight gain, elevated blood creatinine, pain, cognitive impairment, vomiting, cough, and fever.

The most common serious adverse reactions (≥2%) were pulmonary infection (5.2%), dyspnea (4.6%), cognitive impairment (3.8%), pleural effusion (3.0%), and bone fracture (2.4%).4.6% of patients permanently discontinued treatment due to adverse reactions.

[Storage].
Sealed and stored at no more than 30°C.