Selpercatinib

RETEVMO ® is a kinase inhibitor indicated for the treatment of: Adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a rearranged during transfection (RET) gene fusion, as detected by an FDA-approved test. Adult and pediatric patients 2 years of age and older with advanced or metastatic medullary thyroid cancer (MTC) with a RET mutation, as detected by an FDA-approved test, who require systemic therapy. Adult and pediatric patients 2 years of age and older with advanced or metastatic thyroid cancer with a RET gene fusion, as detected by an FDA-approved test, who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).

Selpercatinib is a kinase inhibitor. Selpercatinib inhibited wild-type RET and multiple mutated RET isoforms as well as VEGFR1 and VEGFR3 with IC 50 values ranging from 0.92 nM to 67.8 nM. In other enzyme assays, selpercatinib also inhibited FGFR 1, 2, and 3 at higher concentrations that were still clinically achievable. In cellular assays, selpercatinib inhibited RET at approximately 60-fold lower concentrations than FGFR1 and 2 and approximately 8-fold lower concentration than VEGFR3. Certain point mutations in RET or chromosomal rearrangements involving in-frame fusions of RET with various partners can result in constitutively activated chimeric RET fusion proteins that can act as oncogenic drivers by promoting cell proliferation of tumor cell lines.

Select patients for treatment with RETEVMO based on the presence of a RET gene fusion (NSCLC, thyroid, or other solid tumors) or specific RET gene mutation (MTC). Adult and adolescent patients 12 years of age or older: the recommended dosage is based on weight: Less than 50 kg: 120 mg orally twice daily 50 kg or greater: 160 mg orally twice daily Pediatric patients 2 to less than 12 years of age: the recommended dosage is based on body surface area: 0.33 m 2 to 0.65 m 2: 40 mg orally three times daily 0.66 m 2 to 1.08 m 2: 80 mg orally twice daily 1.09 m 2 to 1.52 m 2: 120 mg orally twice daily ≥1.53 m 2: 160 mg orally twice daily For patients who cannot swallow, disperse 40 mg RETEVMO tablets and administer orally or via gastrostomy or nasogastric tube. Only RETEVMO 40 mg tablets may be used to create the dispersion. Reduce RETEVMO dose in patients with severe hepatic impairment.

None. None.

Hepatotoxicity: Monitor ALT and AST prior to initiating RETEVMO, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce the dose, or permanently discontinue RETEVMO based on severity. Interstitial Lung Disease (ILD)/Pneumonitis: Monitor for new or worsening pulmonary symptoms. Hypertension: Do not initiate RETEVMO in patients with uncontrolled hypertension. Optimize blood pressure (BP) prior to initiating RETEVMO. Monitor BP after 1 week, at least monthly thereafter and as clinically indicated. QT Interval Prolongation: Monitor patients who are at significant risk of developing QTc prolongation. Assess QT interval, electrolytes and TSH at baseline and periodically during treatment.

The following clinically significant adverse reactions are described elsewhere in the labeling: Hepatotoxicity Interstitial Lung Disease / Pneumonitis Hypertension QT Interval Prolongation Hemorrhagic Events Hypersensitivity Tumor Lysis Syndrome Risk of Impaired Wound Healing Hypothyroidism Slipped Capital Femoral Epiphysis/Slipped Upper Femoral Epiphysis in Adolescent Patients The most common adverse reactions (≥25%) include: Adult patients with solid tumors: musculoskeletal pain, edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, rash, nausea, constipation, cough, headache, vomiting, dyspnea, and hemorrhage. Pediatric patients with solid tumors: musculoskeletal pain, diarrhea, nausea, hemorrhage, pyrexia, abdominal pain, headache, vomiting, fatigue, cough, rash, coronavirus infection, upper respiratory tract infection, and edema.

Acid-Reducing Agents: Avoid coadministration. If coadministration cannot be avoided, take RETEVMO with food (with PPI) or modify its administration time (with H2 receptor antagonist or locally-acting antacid). Strong and Moderate CYP3A Inhibitors: Avoid coadministration. If coadministration cannot be avoided, reduce the RETEVMO dose. Strong and Moderate CYP3A Inducers: Avoid coadministration. CYP2C8 and CYP3A Substrates: Avoid coadministration. If coadministration cannot be avoided, modify the substrate dosage as recommended in its product labeling. Certain P-gp and BCRP Substrates: Avoid coadministration.

Store at 20°C to 25°C (68°F to 77°F), excursions between 15°C and 30°C (59°F to 86°F) are permitted.