Pralsetinib

Pralsetinib is a kinase inhibitor of wild-type RET and oncogenic RET fusions (CCDC6- RET ) and mutations ( RET V804L, RET V804M and RET M918T) with half maximal inhibitory concentrations (IC 50s ) less than 0.5 nM. In purified enzyme assays, pralsetinib inhibited DDR1, TRKC, FLT3, JAK1-2, TRKA, VEGFR2, PDGFRB, and FGFR1 at higher concentrations that were still clinically achievable at C max .

• GAVRETO is a kinase inhibitor indicated for treatment of: Adult patients with metastatic rearranged during transfection (RET ) fusion-positive non-small cell lung cancer as detected by an FDA approved test (NSCLC). ( 1.1 ) Adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).ICD-10: C34.90

• None. None.contraindicated

Select patients for treatment with GAVRETO based on the presence of a RET gene fusion. ( 2.1 , 14 ) The recommended dosage in adults and pediatric patients 12 years and older is 400 mg orally once daily on an empty stomach (no food intake for at least 2 hours before and at least 1 hour after taking GAVRETO). ( 2.2 ) 2.1 Patient Selection Select patients for treatment with GAVRETO based on the presence of a RET gene fusion (NSCLC or thyroid cancer) [see Clinical Studies (14) ] . Information on FDA-approved tests for RET gene fusion (NSCLC) is available at http://www.fda.gov/CompanionDiagnostics. An FDA-approved test for the detection of RET gene fusion (thyroid cancer) is not currently available. 2.2 Recommended Dosage The recommended dosage of GAVRETO is 400 mg orally once daily on an empty stomach (no food intake for at least 2 hours before and at least 1 hour after taking GAVRETO ) [see Clinical Pharmacology (12.3) ] . Continue treatment until disease progression or until unacceptable toxicity. If a dose of GAVRETO is missed, it can be taken as soon as possible on the same day. Resume the regular daily dose schedule for GAVRETO the next day. Do not take an additional dose if vomiting occurs after GAVRETO but continue with the next dose as scheduled. 2.3 Dosage Modifications for Adverse Reactions The recommended dose reductions and dosage modifications for adverse reactions are provided in Table 1 and Table 2 .

Serious Infections, Including Opportunistic Infections: Monitor for signs and symptoms of infection and treat appropriately. Withhold, reduce the dose, or permanently discontinue GAVRETO based on severity. ( 2.3 , 5.1 ) Interstitial Lung Disease (ILD)/Pneumonitis: Withhold GAVRETO for Grade 1 or 2 reactions until resolution and then resume at a reduced dose. Permanently discontinue for recurrent ILD/pneumonitis. Permanently discontinue for Grade 3 or 4 reactions. ( 2.3 , 5.2 ) Hypertension : Do not initiate GAVRETO in patients with uncontrolled hypertension. Optimize blood pressure (BP) prior to initiating GAVRETO. Monitor BP after 1 week, at least monthly thereafter and as clinically indicated. Withhold, reduce dose, or permanently discontinue GAVRETO based on severity. ( 2.3 , 5.3 ) Hepatotoxicity : Monitor ALT and AST prior to initiating GAVRETO, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce dose, or permanently discontinue GAVRETO based on severity. ( 2.3 , 5.4 ) Hemorrhagic Events : Permanently discontinue GAVRETO in patients with severe or life-threatening hemorrhage. ( 2.3 , 5.5 ) Tumor Lysis Syndrome: Closely monitor patients at risk and treat as clinically indicated. ( 2.3 , 5.6 ) Risk of Impaired Wound Healing: Withhold GAVRETO for at least 5 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 GAVRETO after resolution of wound healing complications has not been established.

The following clinically significant adverse reactions are described elsewhere in the labeling: Serious Infections, Including Opportunistic Infections [see Warnings and Precautions (5.1) ] Interstitial Lung Disease/Pneumonitis [see Warnings and Precautions (5.2) ] Hypertension [see Warnings and Precautions (5.3) ] Hepatotoxicity [see Warnings and Precautions (5.4) ] Hemorrhagic Events [see Warnings and Precautions (5.5) ] Tumor Lysis Syndrome [see Warnings and Precautions (5.6) ] Risk of Impaired Wound Healing [see Warnings and Precautions (5.7) ] Embryo-Fetal Toxicity [see Warnings and Precautions (5.8) ] The most common adverse reactions (≥ 25%) were musculoskeletal pain, constipation, hypertension, diarrhea, fatigue, edema, pyrexia and cough. The most common Grade 3-4 laboratory abnormalities (≥ 2%) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased phosphate, decreased leukocytes, decreased sodium, increased aspartate aminotransferase (AST), increased alanine aminotransferase (ALT), decreased calcium (corrected), decreased platelets, increased alkaline phosphatase, increased potassium, decreased potassium and increased bilirubin. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Rigel Pharmaceuticals, Inc. at 1-800-983-1329 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

Lactation : Advise not to breastfeed. ( 8.2 ) Pediatric Use : Monitor open growth plates in adolescent patients. Consider interrupting or discontinuing GAVRETO if abnormalities occur. ( 8.4 ) 8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action, GAVRETO can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ]. There are no available data on GAVRETO use in pregnant women to inform drug-associated risk. Oral administration of pralsetinib to pregnant rats during the period of organogenesis resulted in malformations and embryolethality at maternal exposures below the human exposure at the clinical dose of 400 mg once daily (see Data ). 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 2-4% and 15-20%, respectively. Data Animal Data In an embryo-fetal development study, once daily oral administration of pralsetinib to pregnant rats during the period of organogenesis resulted in 100% post-implantation loss at dose levels ≥ 20 mg/kg (approximately 1.8 times the human exposure based on area under the curve [AUC] at the clinical dose of 400 mg).

Metabolism

At 400 mg GAVRETO once daily under fasting conditions, the steady state mean [% coefficient of variation (CV%)] of maximum observed plasma concentration (C max ) and area under the concentration-time curve (AUC 0-24h ) of pralsetinib was 2,470 (55%) ng/mL and 36,700 (66%) h•ng/mL, respectively. Pralsetinib C max and AUC increased inconsistently over the dose range of 60 mg to 600 mg once daily (0.15 to 1.5 times the recommended dose).

• Sep 4, 2020NDANDA213721Rigel Pharms

1. 1Death1448.5%
2. 2Product Prescribing Issue1368.0%
3. 3Fatigue1227.2%
4. 4Asthenia1126.6%
5. 5Off Label Use1116.5%
6. 6Hypertension955.6%
7. 7Anaemia935.5%
8. 8Disease Progression895.2%
9. 9Diarrhoea885.2%
10. 10Blood Pressure Increased834.9%
11. 11Constipation804.7%
12. 12White Blood Cell Count Decreased804.7%
13. 13Pyrexia784.6%
14. 14Pneumonia724.2%
15. 15Platelet Count Decreased543.2%

The 10 most recently updated of 18 ClinicalTrials.gov registrations naming Pralsetinib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study of Multiple Therapies in Biomarker-selected Participants With Resectable Stages IB-III Non-small Cell Lung Cancer (NSCLC)
  Recruiting · Phase 2 · Interventional · 99 enrolled · Genentech, Inc.
  NCT04302025updated 2026-06-09
• Tumor-agnostic Precision Immuno-oncology and Somatic Targeting Rational for You (TAPISTRY) Platform Study
  Active not recruiting · Phase 2 · Interventional · 920 enrolled · Hoffmann-La Roche
  NCT04589845updated 2026-05-08
• Neoadjuvant Umbrella Trial for Patients With Unresectable Stage III NSCLC Harboring Rare Mutations.
  Recruiting · Phase 2 · Interventional · 120 enrolled · Sun Yat-sen University
  NCT06563999updated 2026-04-21
• A Study of Pralsetinib Versus Standard of Care for First-Line Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC)
  Terminated · Phase 3 · Interventional · 223 enrolled · Hoffmann-La Roche
  NCT04222972updated 2026-03-05
• Response to Neoadjuvant Treatment in Locally Advanced Thyroid Cancer
  Recruiting · Observational · 120 enrolled · Fujian Medical University
  NCT07419932updated 2026-02-19
• A Real-world Study of Pralsetinib Combined With Leucogen in the Treatment of RET Fusion-positive NSCLC
  Not yet recruiting · Interventional · 25 enrolled · Fudan University
  NCT07418879updated 2026-02-18
• A Retrospective and Prospective Real-world Study of Molecular Typing in the Treatment of Advanced Thyroid Cancer
  Recruiting · Phase 4 · Interventional · 800 enrolled · Fudan University
  NCT06195228updated 2025-08-14
• A Prospective Cohort Study of Pralsetinib or Anlotinib in the Treatment of Locally Advanced and/or Metastatic Medullary Thyroid Carcinoma With RET Gene Mutations
  Not yet recruiting · Observational · 40 enrolled · Cancer Institute and Hospital, Chinese Academy of Medical Sciences
  NCT07048964updated 2025-07-03
• Genotype-Driven Neoadjuvant Therapy for Locally Advanced Thyroid Cancer: A Real-World Cohort Study
  Not yet recruiting · Phase 4 · Interventional · 335 enrolled · Fujian Medical University
  NCT07010393updated 2025-06-08
• Phase 1/2 Study of the Highly-selective RET Inhibitor, Pralsetinib (BLU-667), in Participants With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors
  Completed · Phase 1 · Phase 2 · Interventional · 590 enrolled · Hoffmann-La Roche
  NCT03037385updated 2025-05-31

Frequently asked questions

How does Pralsetinib work?

Pralsetinib is a kinase inhibitor of wild-type RET and oncogenic RET fusions (CCDC6- RET ) and mutations ( RET V804L, RET V804M and RET M918T) with half maximal inhibitory concentrations (IC 50s ) less than 0.5 nM. In purified enzyme assays, pralsetinib inhibited DDR1, TRKC, FLT3, JAK1-2, TRKA, VEGFR2, PDGFRB, and FGFR1 at higher concentrations that were still clinically achievable at C max .

What is Pralsetinib used for?

According to FDA labeling, Pralsetinib carries indications including: GAVRETO is a kinase inhibitor indicated for treatment of: Adult patients with metastatic rearranged during transfection (RET ) fusion-positive non-small cell lung cancer as detected by an FDA approved test (NSCLC). ( 1.1 ) Adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Pralsetinib?

Pralsetinib is classified as Other protein kinase inhibitors, Kinase Inhibitor, Kinase Inhibitors, Rearranged during Transfection (RET) Inhibitors.

What are the brand names for Pralsetinib?

Pralsetinib is marketed under brand names including Gavreto.

What are the contraindications for Pralsetinib?

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