Retevmo

Non-small cell lung cancer — RET gene fusion-positive, locally advanced or metastatic; Medullary thyroid cancer — RET-mutant, advanced or metastatic requiring systemic therapy (age ≥12 years); Thyroid cancer — RET gene fusion-positive, advanced or metastatic requiring systemic therapy, refractory to radioactive iodine (if applicable); Solid tumors — RET gene fusion-positive, locally advanced or metastatic, progressed on or after prior systemic treatment or with no satisfactory alternative

Weight ≥50 kg: 160 mg orally twice daily
Weight <50 kg: 120 mg orally twice daily
Take with or without food
CYP3A strong inhibitor: Reduce by 50%
Dose reductions: 120 mg BID → 80 mg BID → 40 mg BID (for ≥50 kg)

Capsules: 40 mg, 80 mg

None listed.

• Hepatotoxicity: AST increase in 51%, ALT increase in 45% (Grade 3-4: 8-10%). Monitor LFTs every 2 weeks for 3 months, then monthly. Withhold for Grade 3-4.
• Hypertension: 35% (Grade 3-4: 18%). Control BP before initiation; monitor every 2 weeks for 3 months then monthly.
• QT Prolongation: 6% QTc >500 ms. Monitor ECG and electrolytes at baseline, 1 week, monthly for 3 months, then periodically.
• Hemorrhage: Serious hemorrhage in 2.3%. Permanently discontinue for life-threatening bleeding.
• Hypersensitivity: Including anaphylaxis. Permanently discontinue for Grade 4.
• Impaired Wound Healing: Withhold 7 days before and after elective surgery.
• Hypothyroidism: 19%. Monitor thyroid function.
• Embryo-Fetal Toxicity

Edema (46%), diarrhea (43%), fatigue (42%), dry mouth (39%), hypertension (35%), abdominal pain (30%), constipation (29%), rash (27%), nausea (25%), headache (23%), AST increased (51%), ALT increased (45%)

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

Consult the complete prescribing information for drug interactions, including effects on CYP enzymes, transporters, and concomitant medications that may require dose adjustments or monitoring.

Consult the full prescribing information for pregnancy-related considerations.

Refer to prescribing information for lactation guidance.

Pediatric safety and efficacy information is detailed in the full label.

Dose modifications for organ impairment are specified in the complete prescribing information.

Selpercatinib is a kinase inhibitor targeting wild-type RET (rearranged during transfection), oncogenic RET mutants (including the gatekeeper V804L/M mutations), and RET fusion proteins. It inhibits RET at sub-nanomolar concentrations, blocking RET-mediated cell proliferation. Selpercatinib has minimal activity against VEGFR2 at therapeutic concentrations, differentiating it from multi-kinase inhibitors.

Tmax: 2 hours. Half-life: approximately 32 hours. Protein binding: 97%. Metabolized primarily by CYP3A4. Fecal excretion (69%), urinary excretion (24%).

Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.

• LIBRETTO-001 — Selpercatinib in RET fusion-positive NSCLC and RET-mutant thyroid cancers. Phase I/II, n=531.
  🔬 NCT03157128 ↗ 📄 Primary Publication ↗

Retevmo has FDA-approved indications across the following cancer types covered on PipelineEvidence: