Selpercatinib

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.

• 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 ( 1.1 ) 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 ( 1.2 ) 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) ( 1.3 ) 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 1 ( 1.4 ) 1 This indication is approved under accelerated approval based on overall response rate and duration of response.ICD-10: C34.90

• None. None.contraindicated

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). ( 2.1 , 14 ) Adult and adolescent patients 12 years of age or older : the recommended dosage is based on weight ( 2.3 ): 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 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 ( 2.8 ) Only RETEVMO 40 mg tablets may be used to create the dispersion ( 2.2 ) Reduce RETEVMO dose in patients with severe hepatic impairment. ( 2.7 , 8.7 ) 2.1 Patient Selection Select patients for treatment with RETEVMO based on the presence of a RET gene fusion (NSCLC, thyroid cancer, or other solid tumors) or specific RET gene mutation (MTC) in tumor specimens [see Clinical Studies ( 14 )] . Information on FDA-approved test(s) for the detection of RET gene fusions and RET gene mutations is available at: http://www.fda.gov/CompanionDiagnostics. An FDA-approved companion diagnostic test for the detection of RET gene fusions and RET gene mutations in plasma is not available.

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. ( 2.5 , 5.1 ) Interstitial Lung Disease (ILD)/Pneumonitis : Monitor for new or worsening pulmonary symptoms. Withhold, reduce the dose or permanently discontinue RETEVMO based on severity. ( 2.5 , 5.2 ) 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. Withhold, reduce the dose, or permanently discontinue RETEVMO based on severity. ( 2.5 , 5.3 ) 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 RETEVMO is concomitantly administered with strong and moderate CYP3A inhibitors or drugs known to prolong QTc interval. Withhold and reduce the dose or permanently discontinue RETEVMO based on severity. ( 2.5 , 5.4 ) Hemorrhagic Events: Permanently discontinue RETEVMO in patients with severe or life-threatening hemorrhage. ( 2.5 , 5.5 ) Hypersensitivity: Withhold RETEVMO 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.

The following clinically significant adverse reactions are described elsewhere in the labeling: Hepatotoxicity [see Warnings and Precautions ( 5.1 )] Interstitial Lung Disease / Pneumonitis [see Warnings and Precautions ( 5.2 )] Hypertension [see Warnings and Precautions ( 5.3 )] QT Interval Prolongation [see Warnings and Precautions ( 5.4 )] Hemorrhagic Events [see Warnings and Precautions ( 5.5 )] Hypersensitivity [see Warnings and Precautions ( 5.6 )] Tumor Lysis Syndrome [see Warnings and Precautions ( 5.7 )] Risk of Impaired Wound Healing [see Warnings and Precautions ( 5.8 )] Hypothyroidism [see Warnings and Precautions ( 5.9 )] Slipped Capital Femoral Epiphysis/Slipped Upper Femoral Epiphysis in Adolescent Patients [see Warnings and Precautions ( 5.11 )] 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. ( 6 ) 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. ( 6 ) 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.

Lactation: Advise not to breastfeed. ( 8.2 ) Pediatric Use: Monitor open growth plates in pediatric patients. Consider interrupting or discontinuing RETEVMO if abnormalities occur. ( 8.4 ) 8.1 Pregnancy Risk Summary Based on findings from animal studies, and its mechanism of action [see Clinical Pharmacology ( 12.1 )] , RETEVMO can cause fetal harm when administered to a pregnant woman. There are no available data on RETEVMO use in pregnant women to inform drug-associated risk. Administration of selpercatinib to pregnant rats during the period of organogenesis resulted in embryolethality and malformations at maternal exposures that were approximately equal to the human exposure at the clinical dose of 160 mg twice daily. Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Selpercatinib administration to pregnant rats during the period of organogenesis at oral doses ≥100 mg/kg [approximately 3.6 times the human exposure based on the area under the curve (AUC) at the clinical dose of 160 mg twice daily] resulted in 100% post-implantation loss.

Metabolism

The pharmacokinetics of selpercatinib capsules were evaluated in patients with locally advanced or metastatic solid tumors administered 160 mg twice daily unless otherwise specified. The capsule and tablet dosage forms of selpercatinib are bioequivalent.

• May 8, 2020NDANDA213246Eli Lilly And Co
• Apr 10, 2024NDANDA218160Eli Lilly And Co

1. 1Malignant Neoplasm Progression12610%
2. 2Death1048.3%
3. 3Diarrhoea665.3%
4. 4Hypertension665.3%
5. 5Fatigue584.6%
6. 6Hypersensitivity584.6%
7. 7Rash564.5%
8. 8Pyrexia483.8%
9. 9Hepatic Function Abnormal463.7%
10. 10Electrocardiogram Qt Prolonged393.1%
11. 11Alanine Aminotransferase Increased383.0%
12. 12Aspartate Aminotransferase Increased373.0%
13. 13Ascites362.9%
14. 14Nausea362.9%
15. 15Dry Mouth352.8%

The 10 most recently updated of 39 ClinicalTrials.gov registrations naming Selpercatinib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
  Active not recruiting · Phase 2 · Interventional · 1,377 enrolled · National Cancer Institute (NCI)
  NCT03155620updated 2026-06-01
• Selpercatinib for the Treatment of Advanced Solid Tumors, Lymphomas, or Histiocytic Disorders With Activating RET Gene Alterations, a Pediatric MATCH Treatment Trial
  Active not recruiting · Phase 2 · Interventional · 1 enrolled · National Cancer Institute (NCI)
  NCT04320888updated 2026-05-27
• Selpercatinib Before Surgery for the Treatment of RET-Altered Thyroid Cancer
  Active not recruiting · Phase 2 · Interventional · 30 enrolled · M.D. Anderson Cancer Center
  NCT04759911updated 2026-05-20
• A Study of Selpercatinib (LY3527723) in Participants With Advanced Solid Tumors Including RET Fusion-positive Solid Tumors, Medullary Thyroid Cancer and Other Tumors With RET Activation
  Active not recruiting · Phase 2 · Interventional · 77 enrolled · Eli Lilly and Company
  NCT04280081updated 2026-04-24
• Selpercatinib and Body Composition
  Completed · Observational · 15 enrolled · University of Pisa
  NCT07543887updated 2026-04-22
• A Study of Selpercatinib (LOXO-292) in Participants With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRETTO-001)
  Active not recruiting · Phase 1 · Phase 2 · Interventional · 857 enrolled · Eli Lilly and Company
  NCT03157128updated 2026-04-16
• Selpercatinib Pre-RAI in Patients With RET Fusion Thyroid Cancer (RAISE)
  Recruiting · Phase 2 · Interventional · 13 enrolled · Children's Hospital of Philadelphia
  NCT06458036updated 2026-04-15
• Targeted Treatment for RET Fusion-Positive Advanced Non-Small Cell Lung Cancer (A LUNG-MAP Treatment Trial)
  Active not recruiting · Phase 2 · Interventional · 124 enrolled · SWOG Cancer Research Network
  NCT04268550updated 2026-03-23
• A Study of Selpercatinib (LY3527723) in Participants With RET-Mutant Medullary Thyroid Cancer
  Active not recruiting · Phase 3 · Interventional · 291 enrolled · Loxo Oncology, Inc.
  NCT04211337updated 2026-03-19
• A Study of Selpercatinib After Surgery or Radiation in Participants With Non-Small Cell Lung Cancer (NSCLC)
  Active not recruiting · Phase 3 · Interventional · 152 enrolled · Eli Lilly and Company
  NCT04819100updated 2026-03-04

Frequently asked questions

How does Selpercatinib work?

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.

What is Selpercatinib used for?

According to FDA labeling, Selpercatinib carries indications including: 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 ( 1.1 ) 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 ( 1.2 ) 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) ( 1.3 ) 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 1 ( 1.4 ) 1 This indication is approved under accelerated approval based on overall response rate and duration of response.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Selpercatinib?

Selpercatinib is classified as Other protein kinase inhibitors, Kinase Inhibitor, Breast Cancer Resistance Protein Inhibitors, Cytochrome P450 2C8 Inhibitors, Cytochrome P450 3A Inhibitors, Kinase Inhibitors, Multidrug and Toxin Extrusion Transporter 1 Inhibitors, P-Glycoprotein Inhibitors, Rearranged during Transfection (RET) Inhibitors, Cellular Proliferation Alteration.

What are the brand names for Selpercatinib?

Selpercatinib is marketed under brand names including Retevmo.

What are the contraindications for Selpercatinib?

Selpercatinib labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.