Cabozantinib

In vitro biochemical and/or cellular assays have shown that cabozantinib inhibits the tyrosine kinase activity of RET, MET, VEGFR-1, -2 and -3, KIT, TRKB, FLT-3, AXL, ROS1, TYRO3, MER, and TIE-2. These receptor tyrosine kinases are involved in both normal cellular function and pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, drug resistance, and maintenance of the tumor microenvironment.

• COMETRIQ is indicated for the treatment of patients with progressive, metastatic medullary thyroid cancer (MTC). COMETRIQ is a kinase inhibitor indicated for the treatment of patients with progressive, metastatic medullary thyroid cancer (MTC).

• None None.contraindicated

Recommended Dose: 140 mg orally, once daily. ( 2.1 ) Instruct patients not to eat for at least 2 hours before and at least 1 hour after taking COMETRIQ. ( 2.1 ) Do NOT substitute COMETRIQ capsules with cabozantinib tablets. ( 2.1 ) Hepatic Impairment: The recommended starting dose of COMETRIQ is 80 mg in patients with mild or moderate hepatic impairment. ( 2.1 ) 2.1 Recommended Dosage Do NOT substitute COMETRIQ capsules with cabozantinib tablets. The recommended daily dose of COMETRIQ is 140 mg once daily without food until disease progression or unacceptable toxicity. Instruct patients not to eat for at least 2 hours before and at least 1 hour after taking COMETRIQ. Swallow COMETRIQ capsules whole. Do not open COMETRIQ capsules. Do not take a missed dose within 12 hours of the next dose. Do not ingest foods (e.g., grapefruit, grapefruit juice) or nutritional supplements that are known to inhibit cytochrome P450 while taking COMETRIQ. 2.2 Dosage Modifications for Adverse Reactions Withhold COMETRIQ for NCI CTCAE Grade 4 hematologic adverse reactions, Grade 3 or greater non-hematologic adverse reactions, intolerable Grade 2 adverse reactions, or osteonecrosis of the jaw.

Perforations and Fistulas: Monitor for symptoms. Discontinue COMETRIQ for Grade 4 fistula or perforation. ( 5.1 ) Hemorrhage: Do not administer COMETRIQ if recent history of hemorrhage. ( 5.2 ) Thrombotic Events: Discontinue COMETRIQ for myocardial infarction or serious arterial or venous thromboembolic events. ( 5.3 ) Impaired Wound Healing: Withhold COMETRIQ for at least 3 weeks before elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of COMETRIQ after resolution of wound healing complications has not been established. ( 5.4 ) Hypertension and hypertensive crisis: Monitor blood pressure regularly. Interrupt for hypertension that is not adequately controlled with anti- hypertensive therapy. Discontinue COMETRIQ for hypertensive crisis or severe hypertension that cannot be controlled with anti-hypertensive therapy. ( 5.5 ) Cardiac Failure: Monitor patients for signs and symptoms of cardiac failure throughout treatment. ( 5.6 ) Osteonecrosis of the Jaw (ONJ): Withhold COMETRIQ for at least 3 weeks prior to invasive dental procedure and for development of ONJ. ( 5.7 ) Diarrhea: May be severe. Interrupt COMETRIQ immediately until diarrhea resolves or decreases to Grade 1. Recommend standard antidiarrheal treatments. ( 5.8 ) Palmar-Plantar Erythrodysesthesia (PPE): Interrupt COMETRIQ until PPE resolves or decreases to Grade 1. ( 5.9 ) Proteinuria: Monitor urine protein. Discontinue for nephrotic syndrome.

The following clinically significant adverse reactions are discussed elsewhere in the labeling: Perforations and Fistula [see Warnings and Precautions (5.1) ] Hemorrhage [see Warnings and Precautions (5.2) ] Thromboembolic Events [see Warnings and Precautions (5.3) ] Impaired Wound Healing [see Warnings and Precautions (5.4) ] Hypertension and Hypertensive Crisis [see Warnings and Precautions (5.5) ] Cardiac Failure [see Warnings and Precautions (5.6) ] Osteonecrosis of the Jaw [see Warnings and Precautions (5.7) ] Diarrhea [see Warnings and Precautions (5.8) ] Palmar-Plantar Erythrodysesthesia [see Warnings and Precautions (5.9) ] Proteinuria [see Warnings and Precautions (5.10) ] Reversible Posterior Leukoencephalopathy Syndrome [see Warnings and Precautions (5.11) ] Hypocalcemia [see Warnings and Precautions (5.13) ] The most common adverse reactions (≥ 25%) are diarrhea, stomatitis, palmar-plantar erythrodysesthesia (PPE), decreased weight, decreased appetite, nausea, fatigue, oral pain, hair color changes, dysgeusia, hypertension, abdominal pain, and constipation. The most common laboratory abnormalities (≥ 25%) are increased AST, increased ALT, lymphopenia, increased alkaline phosphatase, hypocalcemia, neutropenia, thrombocytopenia, hypophosphatemia, and hyperbilirubinemia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Exelixis, Inc. at 1-855-500-3935 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Lactation: Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action, COMETRIQ can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )] . There are no available data in pregnant women to inform the drug-associated risk. In animal developmental and reproductive toxicology studies administration of cabozantinib to pregnant rats and rabbits during organogenesis resulted in embryofetal lethality and structural anomalies at exposures that were below those occurring clinically at the recommended dose (see Data ) . Advise pregnant women or women of childbearing potential of the potential hazard to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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 in pregnant rats, daily oral administration of cabozantinib throughout organogenesis caused increased embryo-fetal lethality compared to controls at a dose of 0.03 mg/kg (less than 1% of the human exposure by AUC at the 140 mg dose).

Metabolism

A population pharmacokinetic analysis of cabozantinib was performed using data collected from 289 patients with solid tumors including MTC following oral administration of 140 mg daily doses. Repeat daily dosing of COMETRIQ at 140 mg for 19 days resulted in 4- to 5-fold mean cabozantinib accumulation (based on AUC) compared to a single dose administration; steady state was achieved by Day 15.

One case of overdosage was reported in a patient who inadvertently took twice the intended dose (200 mg daily) for nine days. The patient suffered Grade 3 memory impairment, Grade 3 mental status changes, Grade 3 cognitive disturbance, Grade 2 weight loss, and Grade 1 increase in BUN. The extent of recovery was not documented.

• Nov 29, 2012NDANDA203756Exelixis
• Apr 25, 2016NDANDA208692Exelixis Inc

1. 1Diarrhoea9,36620%
2. 2Fatigue7,62816%
3. 3Off Label Use6,78214%
4. 4Nausea4,94411%
5. 5Decreased Appetite4,5799.7%
6. 6Malignant Neoplasm Progression3,3447.1%
7. 7Blood Pressure Increased3,1776.8%
8. 8Palmar-plantar Erythrodysaesthesia Syndrome3,0796.6%
9. 9Weight Decreased3,0026.4%
10. 10Stomatitis2,8756.1%
11. 11Death2,7815.9%
12. 12Constipation2,3525.0%
13. 13Vomiting2,1984.7%
14. 14Asthenia2,1244.5%
15. 15Blister2,0894.4%

The 10 most recently updated of 294 ClinicalTrials.gov registrations naming Cabozantinib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study to Test the Addition of the Drug Cabozantinib to Chemotherapy in Patients With Newly Diagnosed Osteosarcoma
  Recruiting · Phase 2 · Phase 3 · Interventional · 1,122 enrolled · National Cancer Institute (NCI)
  NCT05691478updated 2026-06-12
• A Clinical Study of Belzutifan and Zanzalintinib in People With Recurrent Kidney Cancer Following Adjuvant Therapy (MK-6482-033)
  Recruiting · Phase 3 · Interventional · 904 enrolled · Merck Sharp & Dohme LLC
  NCT07227402updated 2026-06-12
• Extension Study for Participants in Studies That Include Belzutifan (MK-6482-043/LITESPARK-043)
  Recruiting · Phase 3 · Interventional · 450 enrolled · Merck Sharp & Dohme LLC
  NCT07405164updated 2026-06-12
• Testing Nivolumab and Ipilimumab Immunotherapy With or Without the Targeted Drug Cabozantinib in Recurrent, Metastatic, or Incurable Nasopharyngeal Cancer
  Recruiting · Phase 2 · Interventional · 50 enrolled · National Cancer Institute (NCI)
  NCT05904080updated 2026-06-12
• Cabozantinib S-malate in Treating Patients With Relapsed Osteosarcoma or Ewing Sarcoma
  Active not recruiting · Phase 2 · Interventional · 90 enrolled · National Cancer Institute (NCI)
  NCT02243605updated 2026-06-12
• Testing the Addition of the Anti-cancer Drug, Cabozantinib, to the Usual Immunotherapy Treatment, Avelumab, in Patients With Metastatic Urothelial Cancer, MAIN-CAV Study
  Active not recruiting · Phase 3 · Interventional · 654 enrolled · National Cancer Institute (NCI)
  NCT05092958updated 2026-06-12
• Using Nivolumab Alone or With Cabozantinib to Prevent Mucosal Melanoma Return After Surgery
  Active not recruiting · Phase 2 · Interventional · 101 enrolled · National Cancer Institute (NCI)
  NCT05111574updated 2026-06-11
• Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors
  Active not recruiting · Phase 2 · Interventional · 109 enrolled · National Cancer Institute (NCI)
  NCT02867592updated 2026-06-11
• Testing an Immunotherapy Anti-cancer Drug, Nivolumab, for Advanced Cancers in Patients With Autoimmune Disorders, AIM-NIVO
  Recruiting · Phase 1 · Interventional · 300 enrolled · National Cancer Institute (NCI)
  NCT03816345updated 2026-06-11
• Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors
  Recruiting · Phase 2 · Interventional · 314 enrolled · National Cancer Institute (NCI)
  NCT03866382updated 2026-06-11

Frequently asked questions

How does Cabozantinib work?

In vitro biochemical and/or cellular assays have shown that cabozantinib inhibits the tyrosine kinase activity of RET, MET, VEGFR-1, -2 and -3, KIT, TRKB, FLT-3, AXL, ROS1, TYRO3, MER, and TIE-2. These receptor tyrosine kinases are involved in both normal cellular function and pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, drug resistance, and maintenance of the tumor microenvironment.

What is Cabozantinib used for?

According to FDA labeling, Cabozantinib carries indications including: COMETRIQ is indicated for the treatment of patients with progressive, metastatic medullary thyroid cancer (MTC). COMETRIQ is a kinase inhibitor indicated for the treatment of patients with progressive, metastatic medullary thyroid cancer (MTC).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Cabozantinib?

Cabozantinib is classified as Other protein kinase inhibitors, Kinase Inhibitor, Protein Kinase Inhibitors, Tyrosine Kinase Inhibitors, Cellular Proliferation Alteration.

What are the brand names for Cabozantinib?

Cabozantinib is marketed under brand names including Cabometyx, Cometriq.

What are the contraindications for Cabozantinib?

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