Tucatinib

Tucatinib is a tyrosine kinase inhibitor of HER2. In vitro, tucatinib inhibits phosphorylation of HER2 and HER3, resulting in inhibition of downstream MAPK and AKT signaling and cell proliferation, and showed anti-tumor activity in HER2 expressing tumor cells.

• TUKYSA is a kinase inhibitor indicated: • in combination with trastuzumab and capecitabine for treatment of adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting. ( 1.1 ) • in combination with trastuzumab for the treatment of adult patients with RAS wild-type HER2-positive unresectable or metastatic colorectal cancer that has progressed following treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.ICD-10: C18.9, C50.919

• None. None.contraindicated

• In patients with unresectable or metastatic colorectal cancer, confirm the presence of HER2 protein overexpression and RAS wild-type in tumor specimens prior to the initiation of TUKYSA ( 2.1 ) • Recommended dosage: 300 mg taken orally twice daily with or without food. ( 2.1 ) • For patients with severe hepatic impairment, the recommended dosage is 200 mg orally twice daily. ( 2.3 , 8.7 ) 2.1 Patient Selection Select patients for treatment of unresectable or metastatic colorectal cancer with TUKYSA based on the presence of: • HER2 overexpression or gene amplification [see Clinical Studies (14.2) ]. FDA-approved tests for the detection of HER2 overexpression and gene amplification in patients with unresectable or metastatic colorectal cancer are not currently available, and • RAS wild-type [see Clinical Studies (14.2) ]. Information on FDA-approved tests for the detection of RAS mutations in patients with unresectable or metastatic colorectal cancer is available at http://www.fda.gov/CompanionDiagnostics . 2.2 Recommended Dosage Metastatic Breast Cancer The recommended dosage of TUKYSA is 300 mg taken orally twice daily in combination with trastuzumab and capecitabine until disease progression or unacceptable toxicity [see Clinical Studies (14.1) ] . Unresectable or Metastatic Colorectal Cancer The recommended dosage of TUKYSA is 300 mg taken orally twice daily in combination with trastuzumab until disease progression or unacceptable toxicity [see Clinical Studies (14.2) ].

• Diarrhea : Severe diarrhea, including dehydration, acute kidney injury, and death, has been reported. Administer antidiarrheal treatment as clinically indicated. Interrupt dose, then dose reduce, or permanently discontinue TUKYSA based on severity. ( 2.2 , 5.1 ) • Hepatotoxicity : Severe hepatotoxicity has been reported on TUKYSA. Monitor ALT, AST and bilirubin prior to starting TUKYSA, every 3 weeks during treatment and as clinically indicated. Interrupt dose, then dose reduce, or permanently discontinue TUKYSA based on severity. ( 2.2 , 5.2 ) • Embryo-Fetal Toxicity : TUKYSA can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception. ( 5.3 , 8.1 , 8.3 ) Also, refer to the Full Prescribing Information of trastuzumab and capecitabine for pregnancy and contraception information. 5.1 Diarrhea TUKYSA can cause severe diarrhea including dehydration, hypotension, acute kidney injury, and death [see Adverse Reactions (6.1) ] . If diarrhea occurs, administer antidiarrheal treatment as clinically indicated. Perform diagnostic tests as clinically indicated to exclude other causes of diarrhea. Based on the severity of the diarrhea, interrupt dose, then dose reduce or permanently discontinue TUKYSA [see Dosage and Administration (2.2) ] . TUKYSA with trastuzumab and capecitabine In HER2CLIMB, 81% of patients who received TUKYSA experienced diarrhea, including 0.5% with Grade 4 diarrhea and 12% with Grade 3 diarrhea. Both patients who developed Grade 4 diarrhea subsequently died, with diarrhea as a contributor to death.

The following clinically significant adverse reactions are described elsewhere in the labeling: • Diarrhea [see Warnings and Precautions (5.1) ] • Hepatotoxicity [see Warnings and Precautions (5.2) ] • The most common adverse reactions (≥20%) with TUKYSA in combination with trastuzumab and capecitabine in patients with metastatic breast cancer are diarrhea, palmar-plantar erythrodysesthesia, nausea, hepatotoxicity, vomiting, stomatitis, decreased appetite, anemia, and rash. ( 6.1 ) • The most common adverse reactions (≥20%) with TUKYSA in combination with trastuzumab in patients with unresectable or metastatic colorectal cancer are diarrhea, fatigue, rash, nausea, abdominal pain, infusion related reactions, and pyrexia. To report SUSPECTED ADVERSE REACTIONS, contact Seagen at 1-855-4SEAGEN 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 rates observed in practice. HER2-Positive Metastatic Breast Cancer The safety of TUKYSA in combination with trastuzumab and capecitabine was evaluated in HER2CLIMB [see Clinical Studies (14) ]. Patients received either TUKYSA 300 mg twice daily plus trastuzumab or a non-US approved trastuzumab product, and capecitabine (n=404) or placebo plus trastuzumab or a non-US approved trastuzumab product and capecitabine (n=197).

Lactation : Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary TUKYSA is used in combination with trastuzumab and capecitabine. Refer to the Full Prescribing Information of trastuzumab and capecitabine for pregnancy information. Based on findings in animals and its mechanism of action, TUKYSA can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available human data on TUKYSA use in pregnant women to inform a drug-associated risk. In animal reproduction studies, administration of tucatinib to pregnant rats and rabbits during organogenesis resulted in embryo-fetal mortality, reduced fetal weight and fetal abnormalities at maternal exposures ≥ 1.3 times the human exposure (AUC) at the recommended dose (see Data ) . Advise pregnant women and females of reproductive potential of the potential risk to the fetus. The 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 pilot embryo-fetal development studies, pregnant rats and rabbits received oral doses of tucatinib up to 150 mg/kg/day during the period of organogenesis.

Metabolism

Tucatinib AUC 0-INF and C max increased proportionally over a dosage range from 50 mg to 300 mg (0.17 to 1 times the approved recommended dosage). Time to steady state was approximately 4 days.

• Apr 17, 2020NDANDA213411Seagen

1. 1Diarrhoea1,69725%
2. 2Fatigue91814%
3. 3Nausea89613%
4. 4Vomiting5077.5%
5. 5Off Label Use4697.0%
6. 6Death4456.6%
7. 7Malignant Neoplasm Progression4146.2%
8. 8Palmar-plantar Erythrodysaesthesia Syndrome3885.8%
9. 9Product Dose Omission Issue3595.3%
10. 10Asthenia3535.3%
11. 11Decreased Appetite3024.5%
12. 12Disease Progression2954.4%
13. 13Metastases To Central Nervous System2954.4%
14. 14Dehydration2543.8%
15. 15Neoplasm Progression2523.8%

The 10 most recently updated of 71 ClinicalTrials.gov registrations naming Tucatinib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• ASCEND-CRC: Profiling and Targeting Dynamic Tumor Resistance in Patients With Metastatic Colorectal Cancer
  Not yet recruiting · Early phase 1 · Interventional · 100 enrolled · M.D. Anderson Cancer Center
  NCT07318389updated 2026-06-11
• RO7771950 Versus Tucatinib in Combination With Trastuzumab and Capecitabine in People With Locally Advanced or Metastatic Breast Cancer That is Human Epidermal Growth Factor Receptor 2 (HER2)-Positive
  Recruiting · Phase 2 · Phase 3 · Interventional · 650 enrolled · Hoffmann-La Roche
  NCT07413939updated 2026-06-10
• A Prospective, Multicenter, Observational Cohort Study to Evaluate the Efficacy and Safety of a Novel Anti-tumor Drug as a Radiosensitizer in Patients With Advanced Breast Cancer Brain Metastasis.
  Recruiting · Observational · 100 enrolled · Cancer Institute and Hospital, Chinese Academy of Medical Sciences
  NCT06839547updated 2026-06-10
• A Study of Tucatinib With Trastuzumab and mFOLFOX6 Versus Standard of Care Treatment in First-line HER2+ Metastatic Colorectal Cancer
  Recruiting · Phase 3 · Interventional · 400 enrolled · Seagen, a wholly owned subsidiary of Pfizer
  NCT05253651updated 2026-06-04
• 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
• Study of Patritumab Deruxtecan With Other Anticancer Agents in Participants With HER2 Positive Breast Cancer That Has Spread and Cannot Be Surgically Removed (MK-1022-009)
  Recruiting · Phase 1 · Phase 2 · Interventional · 81 enrolled · Merck Sharp & Dohme LLC
  NCT06686394updated 2026-05-22
• GIM27-THERapy: a Study to Describe the Effectiveness of Tucatinib in Combination With Capecitabine and Trastuzumab in the Treatment of Metastatic HER-2 Positive Breast Cancer Patients in Real World Setting
  Recruiting · Observational · 300 enrolled · Fondazione Oncotech
  NCT07583485updated 2026-05-13
• A Study of Tucatinib and Trastuzumab in People With Rectal Cancer
  Recruiting · Phase 2 · Interventional · 37 enrolled · Memorial Sloan Kettering Cancer Center
  NCT05672524updated 2026-05-12
• Ribociclib, Tucatinib, and Trastuzumab for the Treatment of HER2 Positive Breast Cancer
  Active not recruiting · Phase 1 · Phase 2 · Interventional · 18 enrolled · Jonsson Comprehensive Cancer Center
  NCT05319873updated 2026-05-11
• Pilot Study of [68Ga]Ga-ABY-025 Imaging in Patients Undergoing Treatment With HER2-targeted Therapy
  Recruiting · Early phase 1 · Interventional · 30 enrolled · Vanderbilt-Ingram Cancer Center
  NCT06828588updated 2026-05-08

Frequently asked questions

How does Tucatinib work?

Tucatinib is a tyrosine kinase inhibitor of HER2. In vitro, tucatinib inhibits phosphorylation of HER2 and HER3, resulting in inhibition of downstream MAPK and AKT signaling and cell proliferation, and showed anti-tumor activity in HER2 expressing tumor cells.

What is Tucatinib used for?

According to FDA labeling, Tucatinib carries indications including: TUKYSA is a kinase inhibitor indicated: • in combination with trastuzumab and capecitabine for treatment of adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting. ( 1.1 ) • in combination with trastuzumab for the treatment of adult patients with RAS wild-type HER2-positive unresectable or metastatic colorectal cancer that has progressed following treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Tucatinib?

Tucatinib is classified as Human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitors, Kinase Inhibitor, Cytochrome P450 2C8 Inhibitors, Cytochrome P450 3A Inhibitors, P-Glycoprotein Inhibitors, Tyrosine Kinase Inhibitors, Cellular Proliferation Alteration.

What are the brand names for Tucatinib?

Tucatinib is marketed under brand names including Tukysa.

What are the contraindications for Tucatinib?

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