# Tucatinib

Source: https://onco.cc/drugs/tucatinib/  
OnCo record `tucatinib` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A HER2-selective pill that works in the brain, for HER2-positive breast cancer with brain metastases.

## Summary

Tucatinib is a HER2-selective reversible tyrosine kinase inhibitor that spares EGFR, so it causes less rash and diarrhoea than lapatinib or neratinib, and it penetrates the central nervous system. Taken as 300 mg twice daily, it was approved in 2020 with trastuzumab and capecitabine for HER2-positive metastatic breast cancer after HER2CLIMB, which showed an overall survival benefit that held in patients with active brain metastases, a group usually excluded from trials. In 2023 it was approved with trastuzumab for HER2-positive, RAS-wild-type metastatic colorectal cancer after MOUNTAINEER. Pfizer (via Seagen) markets it. Its place after trastuzumab deruxtecan, which also has brain activity, is the current sequencing question. For a newcomer: the HER2 pill chosen when the cancer has reached the brain.

## Fields

- Kind: Treatment
- Status: approved
- Last checked: 2026-09-04
- Brand: Tukysa
- Modality: Small-molecule kinase inhibitor (HER2)
- Mechanism: Highly HER2-selective reversible TKI sparing EGFR.
- Approvals: US 2020: HER2+ metastatic breast cancer including brain metastases, with trastuzumab and capecitabine; US 2023: HER2+ RAS-wild-type mCRC with trastuzumab; US 2023: HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer that has progressed after fluoropyrimidine, oxaliplatin and irinotecan, with trastuzumab
- Dosing: Oral; 300 mg twice daily with trastuzumab and capecitabine (breast) or trastuzumab (colorectal)

## Notes

- Colorectal cancer biomarkers: eligibility is HER2 amplification or immunohistochemistry 3+ by the colorectal-specific criteria in a RAS wild-type tumour, about 5% of the RAS wild-type population (Valtorta 2015, Richman 2016).

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Tucatinib
- FDA label (DailyMed): https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Tucatinib
- FDA oncology approval notifications: https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancerhematologic-malignancies-approval-notifications

## Connected records

- pairings: [Tucatinib + trastuzumab + capecitabine for brain metastases](https://onco.cc/pairings/tucatinib-triplet-brain-mets/)
- cancers: [Brain metastases (secondary brain tumours)](https://onco.cc/cancers/secondary-brain-tumours/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Early-onset colorectal cancer (under 50)](https://onco.cc/cancers/early-onset-colorectal/), [HER2-amplified colorectal cancer](https://onco.cc/cancers/her2-amplified-colorectal/), [HER2-positive breast cancer](https://onco.cc/cancers/breast-her2-positive/), [HER2-positive breast cancer with brain metastases](https://onco.cc/cancers/her2-positive-breast-brain-metastases/)
- technologies: [HER2 tyrosine kinase inhibitors](https://onco.cc/technologies/her2-tyrosine-kinase-inhibitors/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [HER2](https://onco.cc/targets/her2/)
- companies: [Pfizer (incl. Seagen)](https://onco.cc/companies/pfizer/)
- trials: [A Phase 1b/2 Study of T-DXd Combinations in HER2-positive Metastatic Breast Cancer](https://onco.cc/trials/nct04538742/), [A Study of Disitamab Vedotin With Other Anticancer Drugs in Solid Tumors](https://onco.cc/trials/nct06157892/), [A Study of Tucatinib (MK-7119) in Combination With Trastuzumab and Capecitabine in Participants With Previously Treated Locally Advanced Unresectable or Metastatic Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Breast Carcinoma (MK-7119-001)](https://onco.cc/trials/nct04721977/), [A Study of Tucatinib and Trastuzumab in People With Rectal Cancer](https://onco.cc/trials/nct05672524/), [Basket Study of Tucatinib and Trastuzumab in Solid Tumors With HER2 Alterations](https://onco.cc/trials/nct04579380/), [Cinrebafusp Alfa in Combination With Ramucirumab and Paclitaxel in HER2-High Gastric or GEJ Adenocarcinoma and in Combination With Tucatinib in HER2-Low Gastric or GEJ Andenocarinoma](https://onco.cc/trials/nct05190445/), [Clinical Trial of Alpelisb and Tucatinib in Patients With PIK3CA-Mutant HER2+ Metastatic Breast Cancer.](https://onco.cc/trials/nct05230810/), [HER2CLIMB](https://onco.cc/trials/her2climb/), [HER2CLIMB-02](https://onco.cc/trials/her2climb-02/), [HER2CLIMB-05](https://onco.cc/trials/her2climb-05/), [MOUNTAINEER](https://onco.cc/trials/mountaineer/), [MOUNTAINEER-03](https://onco.cc/trials/mountaineer-03/), [PRE-ISPY Phase I/II Oncology Platform Program](https://onco.cc/trials/nct05868226/), [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)](https://onco.cc/trials/nct06686394/), [Tucatinib Plus Trastuzumab and Oxaliplatin-based Chemotherapy or Pembrolizumab-containing Combinations for HER2+ Gastrointestinal Cancers](https://onco.cc/trials/nct04430738/), [Tucatinib+Trastuzumab+Eribulin in HER2+ MBC](https://onco.cc/trials/nct05458674/)
- key papers: [Assessment of a HER2 scoring system for colorectal cancer: results from a validation study](https://onco.cc/key-papers/paper-valtorta-her2-scoring-colorectal-heracles-mod-pathol-2015/), [HER2 overexpression and amplification as a potential therapeutic target in colorectal cancer: analysis of 3256 patients enrolled in the QUASAR, FOCUS and PICCOLO colorectal cancer trials](https://onco.cc/key-papers/paper-richman-her2-amplification-quasar-focus-piccolo-j-pathol-2016/), [HER2CLIMB brain metastases analysis: intracranial efficacy and survival with tucatinib](https://onco.cc/key-papers/paper-her2climb-brain-lin-jco-2020/), [HER2CLIMB: tucatinib with trastuzumab and capecitabine for HER2-positive metastatic breast cancer, including brain metastases](https://onco.cc/key-papers/paper-her2climb-nejm-2020/), [Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER)](https://onco.cc/key-papers/paper-strickler-mountaineer-tucatinib-trastuzumab-lancet-oncol-2023/)
- terms: [CNS penetration (brain-penetrant drugs)](https://onco.cc/terms/cns-penetration/), [HER2-positive brain metastases](https://onco.cc/terms/her2-brain-metastases/)
- ideas: [Brain metastases included by default in every solid-tumour trial](https://onco.cc/ideas/idea-tr1-brain-mets-default-included/), [Prevention trials aimed only at brain metastasis](https://onco.cc/ideas/idea-bio2-brain-met-prevention-trials/), [Systemic-first management of HER2-positive brain metastases](https://onco.cc/ideas/idea-cns-first-adc-strategy/), [Treat brain metastases as a disease with its own trials programme](https://onco.cc/ideas/idea-fund-brain-metastases-programme/), [Use the brain's own transport door to carry antibody drugs across](https://onco.cc/ideas/idea-bio2-transferrin-shuttle-adc/)
- roadmaps: [Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation](https://onco.cc/roadmaps/colorectal-roadmap/)
- people: [Nancy U. Lin](https://onco.cc/people/nancy-lin/)
- bottlenecks: [The brain: barrier and sanctuary](https://onco.cc/bottlenecks/b-brain-delivery/)
- pathways: [Breast cancer (KEGG map)](https://onco.cc/pathways/breast-cancer-signalling/), [Colorectal cancer (KEGG map)](https://onco.cc/pathways/colorectal-cancer-signalling/), [Organ tropism: seed and soil](https://onco.cc/pathways/organ-tropism-seed-soil/), [The blood-brain barrier & brain metastasis](https://onco.cc/pathways/blood-brain-barrier-metastasis/)
- biomarkers: [HER2 IHC 3+ (HER2-positive by immunohistochemistry)](https://onco.cc/biomarkers/her2-ihc-3-plus/), [RAS wild-type (extended KRAS and NRAS testing)](https://onco.cc/biomarkers/ras-wild-type/)

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JSON: https://onco.cc/api/v1/entities/tucatinib.json