Tukysa (tucatinib)

P2, N=48, Active, not recruiting, Carey Anders, M.D. | Trial primary completion date: Apr 2026 --> Nov 2026 | Trial completion date: Jul 2026 --> Nov 2027

This research aimed to create and validate a new rapid, sensitive, and specific LC-MS/MS technique for measuring tucatinib in dried blood spots (DBS) from mice, with afatinib serving as an internal standard (IS) following regulatory guidelines in the linearity range from 0.178 to 1009 ng/mL (r > 0.990). Tucatinib remained stable under various storage conditions. Comparison of DBS versus plasma samples concentrations showed a strong correlation, suggesting that DBS can serve as a valid alternative to plasma for pharmacokinetic evaluation.

The HER2CLIMB trial demonstrated the benefit of tucatinib, trastuzumab and capecitabine (TTC) in human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC). Treatment discontinuation due to toxicity occurred in 7.4% of participants; there were no treatment-related deaths. In this national real-world cohort, TTC demonstrated clinically meaningful activity and was not associated with any new safety signals in HER2-positive ABC, including patients previously exposed to T-Dxd and those with brain metastases.

Additionally, a 100 ns MD Simulation has resulted in far less deviation, fluctuations, and intermolecular interactions than Tucatinib, suggesting stable protein-ligand interactions, while the binding free energy and total complex energy computed across 0-1000 frames of the MD trajectories indicate that 2-Aoeobenoxmide is a promising in silico candidate. Importantly, because the entire study is computational, the findings should be interpreted as in silico hypotheses, and experimental validation through in vitro and in vivo assays is warranted before any clinical translation is considered.

P3, N=400, Recruiting, Seagen, a wholly owned subsidiary of Pfizer | Trial completion date: Jul 2029 --> Jul 2030 | Trial primary completion date: Apr 2026 --> Dec 2027

Treatment of HER2+ mBC with and without BMs in Saudi Arabia largely aligned with international recommendations identified in our literature analysis, although access to lapatinib, tucatinib and neratinib can be limited and may lead to use of alternative regimens. The tucatinib-combination may be considered the standard of care for adult patients with HER2+ locally advanced or mBC who have received at least two prior anti-HER2+ treatment regimens, including patients with BMs. Ensuring access to innovative HER2+ mBC therapies across Saudi Arabia is crucial to supporting best practice.

Molecular docking identified tucatinib as a brain-penetrant pharmacologic disruptor of FAM3C-SPIN1 interactions, promoting SPIN1 degradation and reducing intracellular proline levels. Thus, cancer stem cells induced a favorable metabolic state through proline synthesis and ROS depletion, revealing potential therapeutic dependencies.

P=N/A, N=300, Recruiting, Fondazione Oncotech

P1/2, N=18, Active, not recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Apr 2027 --> Apr 2028 | Trial primary completion date: Apr 2026 --> Apr 2027 | Recruiting --> Active, not recruiting

P2/3, N=650, Recruiting, Hoffmann-La Roche | Not yet recruiting --> Recruiting

P1/2, N=129, Not yet recruiting, Medica Scientia Innovation Research S.L.

On the basis of 110 ns MD simulations, it was concluded that trilaciclib, tucatinib and olmutinib can be considered candidate inhibitors for HsFN3K inhibition. These drugs are expected to have favourable in-vitro and in-vivo activity inhibiting HsFN3K on the basis of our results. The online version contains supplementary material available at 10.1007/s40203-026-00635-2.