Tukysa (tucatinib)

P2, N=37, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

P2, N=30, Recruiting, Sunnybrook Health Sciences Centre | Trial primary completion date: Oct 2025 --> Dec 2026

Materials & An unanchored, matching-adjusted indirect comparison was conducted following a systematic literature review that identified the CORRECT trial (NCT01103323), which investigated regorafenib, and the RECOURSE trial (NCT01607957), which investigated trifluridine-tipiracil, as comparators for tucatinib in combination with trastuzumab. ORR also favored tucatinib in combination with trastuzumab across analyses. These data support that tucatinib in combination with trastuzumab is an effective therapy option in patients with previously treated mCRC.

Established therapies such as trastuzumab, pertuzumab, trastuzumab/pertuzumab, lapatinib and tucatinib are widely used and are selectively toxic to HER2-positive breast cancer cell line. In conclusion, we demonstrate different time- and concentration-dependent effects of anti-HER2-targeted therapies for the treatment of advanced HER2-positive breast cancer on the BBB in vitro. Further experiments are required to assess the clinical relevance of our results.

We report a 60-year-old woman with HER2-positive, hormone receptor-negative breast cancer who achieved pCR after neoadjuvant docetaxel combined with trastuzumab and pertuzumab, followed by 12 months of maintenance trastuzumab and pertuzumab. Emerging CNS-active therapies, including small-molecule tyrosine kinase inhibitors (TKIs) such as tucatinib and next-generation antibody-drug conjugates (ADCs) like trastuzumab deruxtecan, have shown promising intracranial activity. In addition, advanced strategies such as intensified MRI surveillance, radiomics, liquid biopsy, focused ultrasound-mediated BBB disruption, nanoparticle delivery systems, and radionuclide therapy offer potential avenues for early identification and prevention of cerebral metastases.

Tucatinib plus trastuzumab showed clinically meaningful efficacy and favorable safety. Efficacy was observed irrespective of central HER2+ testing methods and in patients with heterogeneous tumor biomarker profiles.

P2, N=66, Active, not recruiting, Pfizer | Trial completion date: Nov 2025 --> Jun 2026

P1, N=100, Not yet recruiting, M.D. Anderson Cancer Center

Structural modeling and virtual screening validated these proteins as tractable targets, with nilotinib and tucatinib emerging as promising multitarget repurposed drug candidates. At the same time, terfenadine displayed strong binding but cardiotoxic potential. Collectively, these results highlight lipid-driven oncogenesis and ECM remodeling as central to BC biology and provide a translational framework for peptide-based immunotherapy and drug repurposing.

P1, N=1, Terminated, Baptist Health South Florida | N=40 --> 1 | Trial completion date: Feb 2029 --> Dec 2025 | Recruiting --> Terminated | Trial primary completion date: Feb 2028 --> Dec 2025; Slow enrollment

Tumors that express HER2 are susceptible to HER2-targeted therapies, which include inhibitory antibodies such as trastuzumab and pertuzumab, as well as small inhibitor molecules such as lapatinib and tucatinib. Moreover, our detection technology can discriminate between soluble HER2 and membrane-bound HER2, enabling precise identification of the latter. This advancement opens up the possibility of introducing HER2 detection as a highly accurate and quantitative liquid biopsy method for detecting HER2 in blood, in full-length forms, offering new avenues for non-invasive diagnostics, patients monitoring, and early prediction of therapy.

We show that Tucatinib potently inhibits the proliferation and migration of cervical tumor cells in vitro and tumor growth in a mouse xenograft model, while exhibiting excellent biological safety. These findings offer molecular insights into the structural and functional mechanism of MCT2 and identify Tucatinib as novel dual inhibitor of both transporters.