Regorafenib

Regorafenib is a small molecule inhibitor of multiple membrane-bound and intracellular kinases involved in normal cellular functions and in pathologic processes such as oncogenesis, tumor angiogenesis, metastasis and tumor immunity. In in vitro biochemical or cellular assays, regorafenib or its major human active metabolites M-2 and M-5 inhibited the activity of RET, VEGFR1, VEGFR2, VEGFR3, KIT, PDGFR-alpha, PDGFR-beta, FGFR1, FGFR2, TIE2, DDR2, TrkA, Eph2A, RAF-1, BRAF, BRAF V600E, SAPK2, PTK5, Abl and CSF1R at concentrations of regorafenib that have been achieved clinically.

• STIVARGA is a kinase inhibitor indicated for the treatment of adult patients with: • Metastatic colorectal cancer (CRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type, an anti-EGFR therapy. ( 1.1 ) • Locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) who have been previously treated with imatinib mesylate and sunitinib malate.ICD-10: C18.9

• None. None.contraindicated

• Recommended dose: 160 mg orally, once daily for the first 21 days of each 28-day cycle. ( 2.1 ) • Take STIVARGA after a low-fat meal. ( 2.1 , 12.3 ) 2.1 Recommended Dose The recommended dose is 160 mg STIVARGA (four 40 mg tablets) taken orally once daily for the first 21 days of each 28-day cycle. Continue treatment until disease progression or unacceptable toxicity. Take STIVARGA at the same time each day. Swallow tablet whole with water after a low-fat meal that contains less than 600 calories and less than 30% fat [see Clinical Pharmacology ( 12.3 )] . Do not take two doses of STIVARGA on the same day to make up for a missed dose from the previous day. 2.2 Dose Modifications If dose modifications are required, reduce the dose in 40 mg (one tablet) increments; the lowest recommended daily dose of STIVARGA is 80 mg daily.

• Hepatotoxicity : Monitor liver function tests. Withhold and then reduce or discontinue STIVARGA based on severity and duration. ( 5.1 ) • Infections : Withhold STIVARGA in patients with worsening or severe infections. ( 5.2 ) • Hemorrhage : Permanently discontinue STIVARGA for severe or life-threatening hemorrhage. ( 5.3 ) • Gastrointestinal perforation or fistula : Discontinue STIVARGA. ( 5.4 ) • Dermatologic toxicity : Withhold and then reduce or discontinue STIVARGA depending on severity and persistence of dermatologic toxicity. ( 5.5 ) • Hypertension : Temporarily or permanently withhold STIVARGA for severe or uncontrolled hypertension. ( 5.6) • Cardiac ischemia and infarction : Withhold STIVARGA for new or acute cardiac ischemia/infarction and resume only after resolution of acute ischemic events. ( 5.7) • Reversible posterior leukoencephalopathy syndrome (RPLS) : Discontinue STIVARGA. ( 5.8) • Risk of impaired wound healing : Withhold for at least 2 weeks prior to elective surgery. Do not administer for at least 2 weeks after major surgery and until adequate wound healing. The safety of resumption of STIVARGA after resolution of wound healing complications has not been established. ( 5.9 ) • Embryo-fetal toxicity : Can cause fetal harm. Advise women of potential risk to a fetus and to use effective contraception during treatment and for 2 months after the final dose. Advise males to use effective contraception for 2 months after the final dose.

The following serious adverse reactions are discussed elsewhere in the labeling: • Hepatotoxicity [see Warnings and Precautions ( 5.1 )] • Infections [see Warnings and Precautions ( 5.2 )] • Hemorrhage [see Warnings and Precautions ( 5.3 )] • Gastrointestinal Perforation or Fistula [see Warnings and Precautions ( 5.4 )] • Dermatological Toxicity [see Warnings and Precautions ( 5.5 )] • Hypertension [see Warnings and Precautions ( 5.6 )] • Cardiac Ischemia and Infarction [see Warnings and Precautions ( 5.7 )] • Reversible Posterior Leukoencephalopathy Syndrome (RPLS) [see Warnings and Precautions ( 5.8 )] The most common adverse reactions (≥20%) are pain (including gastrointestinal and abdominal pain), HFSR, asthenia/fatigue, diarrhea, decreased appetite/food intake, hypertension, infection, dysphonia, hyperbilirubinemia, fever, mucositis, weight loss, rash, and nausea. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Bayer HealthCare Pharmaceuticals Inc. at 1-888-842-2937 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rate observed in practice.

Nursing Mothers: Discontinue drug or nursing, taking into consideration the importance of the drug to the mother. ( 8.3 ) 8.1 Pregnancy Risk Summary Based on animal studies and its mechanism of action, STIVARGA can cause fetal harm when administered to a pregnant woman. There are no available data on STIVARGA use in pregnant women. Administration of regorafenib was embryolethal and teratogenic in rats and rabbits at exposures lower than human exposures at the recommended dose, with increased incidences of cardiovascular, genitourinary, and skeletal malformations [see Data ] . Advise pregnant women 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 to 4 % and 15 to 20%, respectively. Data Animal Data In embryo-fetal development studies, a total loss of pregnancy (100% resorption of litter) was observed in rats at doses as low as 1 mg/kg (approximately 6% of the recommended human dose, based on body surface area) and in rabbits at doses as low as 1.6 mg/kg (approximately 25% of the human exposure at the clinically recommended dose measured by AUC).

Metabolism

Absorption Following a single 160 mg dose of STIVARGA in patients with advanced solid tumors, regorafenib reaches a geometric mean peak plasma level (C max ) of 2.5 µg/mL at a median time of 4 hours and a geometric mean area under the plasma concentration vs. time curve (AUC) of 70.4 µg*h/mL.

The highest dose of STIVARGA studied clinically is 220 mg per day. The most frequently observed adverse drug reactions at this dose were dermatological events, dysphonia, diarrhea, mucosal inflammation, dry mouth, decreased appetite, hypertension, and fatigue. There is no known antidote for STIVARGA overdose. In the event of suspected overdose, interrupt STIVARGA, institute supportive care, and observe until clinical stabilization.

• Sep 27, 2012NDANDA203085Bayer Hlthcare

1. 1Off Label Use2,05918%
2. 2Fatigue1,76215%
3. 3Palmar-plantar Erythrodysaesthesia Syndrome1,43213%
4. 4Diarrhoea1,41012%
5. 5Decreased Appetite1,0859.5%
6. 6Death9918.7%
7. 7Asthenia9418.2%
8. 8Dysphonia8207.2%
9. 9Nausea8097.1%
10. 10Pain In Extremity7706.7%
11. 11Pyrexia7486.5%
12. 12Hypertension6916.0%
13. 13Weight Decreased6335.5%
14. 14Vomiting5695.0%
15. 15Rash5534.8%

The 10 most recently updated of 361 ClinicalTrials.gov registrations naming Regorafenib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Trial to Evaluate Multiple Regimens in Newly Diagnosed and Recurrent Glioblastoma
  Recruiting · Phase 2 · Phase 3 · Interventional · 2,250 enrolled · Global Coalition for Adaptive Research
  NCT03970447updated 2026-06-12
• The Application of Locoregional Therapy Combined With Systemic Therapy in the Perioperative Period of Huge Hepatocellular Carcinoma: A Retrospective Cohort Study
  Completed · Observational · 715 enrolled · Tongji Hospital
  NCT07639294updated 2026-06-10
• Efficacy and Safety of NB003 in Patients With Advanced Gastrointestinal Stromal Tumors (GIST)
  Recruiting · Phase 2 · Phase 3 · Interventional · 255 enrolled · Ningbo Newbay Technology Development Co., Ltd
  NCT07379047updated 2026-06-10
• A Study of Cadonilimab Combined With Regorafenib in Patients With Advanced HCC
  Completed · Phase 1 · Phase 2 · Interventional · 36 enrolled · Sun Yat-sen University
  NCT05773105updated 2026-06-10
• RegoNivo vs Standard of Care Chemotherapy in AGOC
  Completed · Phase 3 · Interventional · 462 enrolled · Australasian Gastro-Intestinal Trials Group
  NCT04879368updated 2026-06-10
• Clinical Study of Novel Therapeutic Vaccine for Advanced Solid Tumors
  Recruiting · Phase 1 · Interventional · 54 enrolled · West China Hospital
  NCT07567222updated 2026-06-09
• Regorafenib (Reg) and Lorigerlimab (Lor), RELO Regimen, in Treatment of High-risk Patients With Colorectal Cancer With Radiographic Occult Molecular Residual Disease After End of Established Definitive Therapy [ReLOAD Trial]
  Suspended · Phase 2 · Interventional · 16 enrolled · M.D. Anderson Cancer Center
  NCT07071961updated 2026-06-05
• Efficacy and Safety of Hepatic Arterial Infusion Chemotherapy Combined With Tislelizumab and Regorafenib as First-Line Therapy for Advanced Cholangiocarcinoma
  Completed · Phase 2 · Interventional · 31 enrolled · The First Affiliated Hospital of Zhengzhou University
  NCT07619937updated 2026-06-02
• TAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer
  Recruiting · Phase 2 · Interventional · 4,200 enrolled · American Society of Clinical Oncology
  NCT02693535updated 2026-05-29
• Lenvatinib or Regorafenib for Advanced Hepatocellular Carcinoma After Immunotherapy (REVIVE)
  Not yet recruiting · Phase 2 · Interventional · 146 enrolled · Asan Medical Center
  NCT07495579updated 2026-05-27

Frequently asked questions

How does Regorafenib work?

Regorafenib is a small molecule inhibitor of multiple membrane-bound and intracellular kinases involved in normal cellular functions and in pathologic processes such as oncogenesis, tumor angiogenesis, metastasis and tumor immunity. In in vitro biochemical or cellular assays, regorafenib or its major human active metabolites M-2 and M-5 inhibited the activity of RET, VEGFR1, VEGFR2, VEGFR3, KIT, PDGFR-alpha, PDGFR-beta, FGFR1, FGFR2, TIE2, DDR2, TrkA, Eph2A, RAF-1, BRAF, BRAF V600E, SAPK2, PTK5, Abl and CSF1R at concentrations of regorafenib that have been achieved clinically.

What is Regorafenib used for?

According to FDA labeling, Regorafenib carries indications including: STIVARGA is a kinase inhibitor indicated for the treatment of adult patients with: • Metastatic colorectal cancer (CRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type, an anti-EGFR therapy. ( 1.1 ) • Locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) who have been previously treated with imatinib mesylate and sunitinib malate.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Regorafenib?

Regorafenib is classified as Other protein kinase inhibitors, Kinase Inhibitor, Breast Cancer Resistance Protein Inhibitors, Cytochrome P450 2C9 Inhibitors, Kinase Inhibitors, UGT1A1 Inhibitors, UGT1A9 Inhibitors, Cellular Proliferation Alteration, Vascular Growth Decrease.

What are the brand names for Regorafenib?

Regorafenib is marketed under brand names including Stivarga.

What are the contraindications for Regorafenib?

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