ALISERPATINIB Selpercatinib

[Product Name] Selpercatinib Capsules

[Other Names] Selpercatinib / LOXO-292

[English Name] Selpercatinib Capsules

[Specification] 40 mg × 120 capsules/box

[Manufacturer] Lao Pharmaceutical Group Co., Ltd.

[Approval Number] (Lao National Drug Administration): 11 L 1233/24

The anticancer drug LOXO-292 (Selpercatinib) is a kinase inhibitor. Selpercatinib (LOXO-292) inhibits wild-type RET and various mutant RET subtypes, as well as VEGFR1 and VEGFR3, with IC50 values ranging from 0.92 nM to 67.8 nM. When using Selpercatinib, patients must be selected for treatment based on the presence of RET gene fusions (in NSCLC or thyroid cancer) or specific RET gene mutations (in MTC). For patients with severe hepatic impairment, the dosage of Selpercatinib (LOXO-292) should be appropriately reduced during treatment based on the patient's specific clinical condition; however, the exact dosage should ultimately be determined based on a physician's advice. Treatment should continue until the patient no longer derives clinical benefit from the therapy or until drug resistance develops. During this period, patients must not independently increase, decrease, or discontinue the use of Selpercatinib.

[Indications]

1. Adult patients with metastatic RET fusion-positive non-small cell lung cancer (NSCLC);

2. Adult and pediatric patients aged ≥12 years with advanced or recurrent RET-mutant medullary thyroid cancer (MTC) requiring systemic therapy;

3. Adult and pediatric patients aged ≥12 years with advanced or metastatic RET fusion-positive thyroid cancer requiring systemic therapy and who are refractory to radioactive iodine (if radioactive iodine is appropriate).

[Dosage and Administration]

Recommended dosage based on body weight: ① < 50 kg: 120 mg; ② ≥ 50 kg: 160 mg. Administer orally twice daily (approximately every 12 hours) until disease progression or unacceptable toxicity occurs. Swallow the capsules whole; do not crush or chew the capsule shell.

Do not miss any doses unless more than 6 hours have elapsed since the scheduled time for the next dose. If vomiting occurs after taking the medication, do not take a replacement dose; continue with the next scheduled dose at the regular interval.

【Mechanism of Action】

Selpercatinib is a potent, orally bioavailable, and highly selective inhibitor of the rearranged during transfection (RET) kinase, indicated for the treatment of patients with cancers harboring RET alterations. The RET gene is a proto-oncogene that undergoes rearrangement during the process of transfection—hence its name—and encodes a cell-surface receptor tyrosine kinase; alterations in this gene serve as rare oncogenic drivers in various types of tumors.

【Side Effects】

Fatigue, edema, thrombocytopenia, dry mouth, diarrhea, rash, hyponatremia, elevated creatinine, elevated alkaline phosphatase, hypertension, elevated total cholesterol, constipation.

【Precautions】

1. Hemorrhagic Events: This medication may cause serious, including fatal, hemorrhagic events. Patients experiencing severe or life-threatening hemorrhage should permanently discontinue this medication.

2. Hypersensitivity Reactions: Symptoms may include fever, rash, arthralgia, and myalgia, accompanied by thrombocytopenia or elevated transaminase levels. If a hypersensitivity reaction occurs, temporarily withhold the medication and initiate corticosteroid therapy at a dose of 1 mg/kg. Once the hypersensitivity reaction has resolved, reduce the dosage of this medication and re-escalate the dose weekly, based on tolerability, until the dose administered prior to the onset of the hypersensitivity reaction is reached.

3. Impaired Wound Healing: This medication possesses anti-angiogenic properties and may impair wound healing. Withhold the medication for at least one week prior to undergoing elective surgery. Do not administer this medication for at least 2 weeks following major surgery, or until the surgical incision has completely healed. The safety of resuming this medication after the resolution of wound healing complications has not been established.

4. Embryo-Fetal Toxicity: Animal studies have demonstrated that Selpercatinib causes embryo-fetal toxicity. Patients and their partners should use effective contraception during treatment and for one week following the discontinuation of the medication.