HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use LUCISEL safely and effectively. See full prescribing information for LUCISEL.

INDICATIONS AND USAGE

LUCISEL 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). 

• Adult and pediatric patients 2 years of age and older with locally advanced or metastatic solid tumors with a RET gene fusion, as detected by an FDA-approved test, that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options.

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

DOSAGE AND ADMINISTRATION

• Select patients for treatment with LUCISEL 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 (2.3):

• 0.33 to 0.65 m2: 40 mg orally three times daily

• 0.66 to 1.08 m2: 80 mg orally twice daily

• 1.09 to 1.52 m2: 120 mg orally twice daily

• ≥1.53 m2: 160 mg orally twice daily

• Reduce LUCISEL dose in patients with severe hepatic impairment.

DOSAGE FORMS AND STRENGTHS

Capsules: 40 mg×120 capsules

CONTRAINDICATIONS

None.

WARNINGS AND PRECAUTIONS

• Hepatotoxicity: Monitor ALT and AST prior to initiating LUCISEL, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce the dose, or permanently discontinue LUCISEL based on severity.

• Interstitial Lung Disease (ILD)/Pneumonitis: Monitor for new or worsening pulmonary symptoms. Withhold, reduce the dose or permanently discontinue LUCISEL based on severity.

• Hypertension: Do not initiate LUCISEL in patients with uncontrolled hypertension. Optimize blood pressure (BP) prior to initiating LUCISEL. Monitor BP after 1 week, at least monthly thereafter and as clinically indicated. Withhold, reduce the dose, or permanently discontinue LUCISEL based on severity.

• 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. Monitor QT interval more frequently when LUCISEL is concomitantly administered with strong and moderate CYP3A inhibitors or drugs known to prolong QTc interval. Withhold and reduce the dose or permanently discontinue LUCISEL based on severity.

• Hemorrhagic Events: Permanently discontinue LUCISEL in patients with severe or life-threatening hemorrhage.

• Hypersensitivity: Withhold LUCISEL and initiate corticosteroids. Upon resolution, resume at a reduced dose and increase dose by 1 dose level each week until reaching the dose taken prior to onset of hypersensitivity. Continue steroids until patient reaches target dose and then taper.

• Tumor Lysis Syndrome: Closely monitor patients at risk and treat as clinically indicated.

• Risk of Impaired Wound Healing: Withhold LUCISEL for at least 7 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of LUCISEL after resolution of wound healing complications has not been established.

• Hypothyroidism: Monitor thyroid function before treatment with LUCISEL and periodically during treatment. Withhold until clinically stable or permanently discontinue based on severity.

• Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the possible risk to a fetus and to use effective contraception.  

• Slipped Capital Femoral Epiphysis/Slipped Upper Femoral Epiphysis (SCFE/SUFE) in Pediatric Patients: Monitor patients for symptoms indicative of SCFE/SUFE and treat as medically and surgically appropriate.

ADVERSE REACTIONS

The most common adverse reactions (≥25%) include:

·  Adult patients with solid tumors: edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache.

·  Pediatric patients with solid tumors: musculoskeletal pain, diarrhea, headache, nausea, vomiting, coronavirus infection, abdominal pain, fatigue, pyrexia, and hemorrhage.

The most common Grade 3 or 4 laboratory abnormalities (≥5%) include:

· Adult patients with solid tumors: decreased lymphocytes, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), decreased sodium, and decreased calcium.

·  Pediatric patients with solid tumors: decreased calcium, decreased hemoglobin, and decreased neutrophils.

DRUG INTERACTIONS

• Acid-Reducing Agents: Avoid coadministration. If coadministration cannot be avoided, take LUCISEL 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 LUCISEL 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 Substrates: Avoid coadministration. If coadministration cannot be avoided, modify the substrate dosage as recommended in its product labeling.

USE IN SPECIFIC POPULATIONS

• Lactation: Advise not to breastfeed.

• Pediatric Use: Monitor open growth plates in pediatric patients. Consider interrupting or discontinuing LUCISEL if abnormalities occur.

Storage

Store at 20℃ to 25℃ (68℉ to 77℉), excursions permitted between 15℃ and 30℃ (59℉ and 86℉) [see USP Controlled Room Temperature]. Protect from moisture.