Enrectinib is a specific tyrosine kinase inhibitor designed for the fusion of NTRK and ROS1 genes, used to treat NTRK fusion-positive locally advanced or metastatic solid tumors.

Entecavir Instructions

Product Name: LuciEntre

Manufacturer: Lucius Pharmaceuticals

Chinese name: Entrectinib

English name: Entrectinib

Drug approval number: 03 L 1075/24

 

 

【Summary】

Entrectinib is a specific tyrosine kinase inhibitor designed for the fusion of NTRK and ROS1 genes and is used to treat NTRK fusion-positive locally advanced or metastatic solid tumors.

 

【Indications】

1. Adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are ROS1-positive.
2. Adults and children aged 12 years and older with solid tumors who:
① Have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation;
② Metastatic disease or surgical resection may lead to serious complications;
③ There is progression after treatment or there is no satisfactory alternative treatment.

 

【Specification】

100mg/capsule, 60 capsules/bottle

【Storage】

Store in a dry place at 20°C to 25°C. Excursions to temperatures of 15–30°C (59–86°F) are permitted.

 

【Usage and Dosage】

1. Recommended dose for ROS1-positive non-small cell lung cancer: 600 mg orally, once a day.
2. Recommended dose for NTRK gene fusion-positive solid tumors:
① Adults: 600 mg orally, once a day;
② For pediatric patients aged 12 years and above: The recommended dose is based on body surface area (BSA) as follows:
• BSA greater than 1.50 m2: 600 mg orally, once a day;
• BSA 1.11 to 1.50 m2: 500 mg orally, once a day;
• BSA 0.91 to 1.10 m2: 400 mg orally, once a day.

【Adverse Reactions】

1. Common:

1) Abdominal or stomach pain or tenderness, blurred vision, burning, or a crawling sensation.

2) Itching, numbness, tingling, "pins and needles" or stinging sensations, changes in color vision.

3) Clay-colored stools, confusion, dark urine, decreased appetite, and defects (intelligence, short-term memory, learning ability, and attention).

4) Difficulty with night vision, dizziness, fever, headache, and increased sensitivity of the eyes to sunlight.

5) Skin rash, joints (pain, stiffness or swelling), loss of appetite, back pain, side pain.

6) Nausea and vomiting, balance problems, drowsiness or unusual sleepiness, swelling in the feet or lower legs.

7) Difficulty sleeping, unusual tiredness or weakness, yellowing eyes or skin.

2. Uncommon:

1) Chest pain, decreased urine output, jugular vein distension, and diplopia.

2) Extreme fatigue, fainting, irregular breathing, and irregular heartbeat recurred.

3) Amnesia, memory problems, speech problems, (seeing, hearing, or feeling things that are not there), swelling (of the face, fingers, feet, or lower legs).

4) Chest tightness, memory difficulties, breathing difficulties, and weight gain.

 

【 Notes 】

1. Congestive heart failure: Among the 355 patients who received entrectinib in clinical trials, the incidence of congestive heart failure (CHF) was 3.4%, including grade 3 (2.3%).

2. Central nervous system effects: Patients treated with entrectinib experienced a wide range of central nervous system (CNS) adverse reactions, including cognitive impairment, mood disorders, dizziness, and sleep disorders.

3. Fracture: Entrectinib increases the risk of fracture. In an expanded safety trial, 338 adult patients and 30 pediatric patients were treated with Entrectinib, and 5% of adult patients and 23% of pediatric patients experienced fractures.

4. Hepatotoxicity: Among the 355 patients treated with entrectinib, 42% of the patients had varying degrees of AST elevation and 36% of the patients had varying degrees of ALT elevation. Grade 3-4 AST or ALT elevation occurred in 2.5% and 2.8% of the patients, respectively; since 4.5% of the patients did not undergo liver function tests after treatment, their incidence may be underestimated.

5. Hyperuricemia: Among the 355 patients who received clinical trials of entrectinib, 32 patients (9%) developed hyperuricemia, accompanied by symptoms and elevated uric acid levels.

6. QT interval prolongation: After taking entrectinib, 3.1% of 355 patients had at least one post-baseline electrocardiogram assessment of QTcF interval prolongation >60ms, and 0.6% of patients had a QTcF interval >500ms.

7. Visual impairment: Among the 355 patients in the clinical trial of entrectinib, 21% of the patients experienced visual changes, including Grade 1 (82%), Grade 2 (14%), and Grade 3 (0.8%).

8. Embryotoxicity: Based on literature reports of human congenital mutations leading to changes in TRK signaling, findings from animal experiments, and its mechanism of action, entrectinib may cause harm to the fetus when taken by pregnant women.

 

【 Mechanism of action 】

Entrectinib is an inhibitor of the tropomyosin receptor tyrosine kinases ( TRKs ) TRKA , TRKB , and TRKC (encoded by the neurotrophic tyrosine receptor kinase [NTRK] genes NTRK1 , NTRK2 , and NTRK3 , respectively ), the proto-oncogene tyrosine protein kinase ROS1 ( ROS1 ), and anaplastic lymphoma kinase ( ALK ) with IC50 values ​​ranging from 0.1 to 2 nM . Entrectinib also inhibits JAK2 and TNK2 with IC50 values ​​>5 nM . The major active metabolite of entrectinib, M5, has similar in vitro activity against TRK , ROS1 , and ALK .

 

Safety and efficacy

1. ROS1-positive non-small cell lung cancer

The efficacy of entrectinib was evaluated in a combined subgroup of patients with ROS1- positive metastatic NSCLC who received different doses and schedules of entrectinib ( 90% 600 mg orally once daily ) and were enrolled in one of three multicenter, single-arm, open-label clinical trials: ALKA , STARTRK-1 ( NCT02097810 ), and STARTRK-2 ( NCT02568267 ).

The efficacy of 51 patients with ROS1- positive NSCLC was evaluated. The overall response rate was 78% , including 6% complete response and 73% partial response ; the duration of response ( DOR ) ≥ 9 months, ≥ 12 months, and ≥ 18 months were 70% , 55% , and 30% , respectively .

2. NTRK gene fusion-positive solid tumors

The efficacy of entrectinib was evaluated in a pooled subgroup of adult patients with unresectable or metastatic solid tumors harboring NTRK gene fusions who were enrolled in three multicenter, single-arm, open-label clinical trials: ALKA , STARTRK-1 ( NCT02097810 ), and STARTRK-2 ( NCT02568267 ).

The efficacy of the drug was evaluated in 54 adult patients with NTRK gene fusion solid tumors. The overall response rate was 57% , including 7.4% complete response and 50% partial response ; the duration of response ( DOR ) ≥ 6 months, ≥ 9 months, and ≥ 12 months were 68% , 61% , and 45% , respectively .