Tukysa (tucatinib)

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.

P2, N=13, Terminated, Spanish Breast Cancer Research Group | Trial completion date: Aug 2026 --> May 2025 | Active, not recruiting --> Terminated | Trial primary completion date: Aug 2026 --> May 2025; The study was closed early due to safety concerns and an unfavorable benefit-risk balance. Unexpected high neutropenia rates required a costly sub-study, which was not feasible, forcing the sponsor to terminate the trial prematurely.

Tucatinib addition to trastuzumab and pertuzumab demonstrated improvement in PFS with no new safety signals identified and may be an option for 1L maintenance therapy in patients with HER2+ MBC.

Among these, LTS0131923 demonstrated the highest binding affinity against HER2 (PDB ID: 7MN5), with a binding energy of -11.2 kcal/mol and an inhibition constant of 0.00626 μM, outperforming Tucatinib, a standard CRC treatment. This study reveals the potential of ML-driven approaches to accelerate the discovery of dual-target inhibitors for CRC therapy and highlights Ceratonia siliqua L. as a promising source of bioactive compounds for cancer treatment.

P=N/A, N=49, Completed, iOMEDICO AG | Recruiting --> Completed | N=300 --> 49 | Trial completion date: May 2027 --> Jun 2025 | Trial primary completion date: May 2027 --> Jun 2025

Hb 100 ng/mL, height >160 cm, and the presence of lymph node metastases were associated with HER2 expression and positivity. HER2 testing should be considered mandatory when all these factors are present. The mechanisms linking these four factors to HER2 expression require further investigation.

This trial has been approved by the Institutional Review Board (IRB) and began patient enrollment in January 2024. The trial will provide insights into the safety and effectiveness of a novel combinatorial therapy for BCBM.

Our model, based on NIH 3T3 cells, became sensitive to the monoclonal antibody trastuzumab and to the selective HER2 tyrosine kinase inhibitor tucatinib. The results suggest that this model could be a promising tool for preclinical functional cross-reactivity tests of anti-HER2 therapies before in vivo studies.

The addition of tucatinib to T-DM1 improved PFS in patients with previously treated HER2+ LA/MBC, including patients with BMs, and exhibited a manageable safety profile.

P=N/A, N=93, Completed, Pfizer | Active, not recruiting --> Completed

P=N/A, N=600, Not yet recruiting, Pfizer | Trial completion date: Jun 2030 --> May 2029 | Trial primary completion date: Jun 2030 --> May 2029