P1, N=34, Active, not recruiting, Debiopharm International SA | Trial completion date: Jul 2026 --> Feb 2026

We treated ER+ MCF7 breast cancer cells with palbociclib alternating with a combination of fulvestrant and WEE1 inhibitor AZD1775 for 12 months. We developed a mathematical model that can simulate cell proliferation under monotherapy and alternating drug treatments. Finally, we showed that the mathematical model can be used to minimize the number of fulvestrant plus AZD1775 treatment periods while maintaining its efficacy.

P1, N=34, Active, not recruiting, Debiopharm International SA | Recruiting --> Active, not recruiting | N=78 --> 34

The efficacy of the mouse double minute 2 homolog (MDM2) inhibitor (HDM201) and the Wee1 G2 checkpoint kinase (Wee1) inhibitor (adavosertib) was confirmed in both p53 wild-type (p53 WT) and p53 mutant (p53 MT) GIST cells. Our results highlight the importance of p53 status in guiding GIST treatment. p53 WT tumors respond to MDM2 inhibitors, while p53 MT tumors show greater sensitivity to Wee1 inhibitors, supporting p53 pathway targeting as a promising strategy for GIST patients.

P1, N=155, Active, not recruiting, Debiopharm International SA | Recruiting --> Active, not recruiting

Risk model analysis predicted differential treatment responses: low-risk patients exhibited superior anti-PD-1 immunotherapy responses, whereas high-risk patients showed increased sensitivity to DNA-damaging agents (e.g., the Wee1 inhibitor MK-1775) and sorafenib. Plasma exosomal lncRNAs enable robust molecular subtyping, accurate prognostic stratification, and treatment response prediction in HCC. The ERG-centric classification system and validated 6-gene risk model provide clinically actionable tools for precision oncology.

P1, N=13, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2025 --> Sep 2026

Using a pooled CRISPRi screen, we identify GSPT1 and ALKBH8 as factors whose depletion confer hypersensitivity to the WEE1 inhibitor, AZD1775...This dual mechanism highlights opportunities for combination therapies, such as pairing WEE1 inhibitors with agents targeting the mRNA translation machinery. This study also underscores the need for more precise WEE1 targeting strategies to mitigate off-target effects, with implications for optimising the therapeutic potential of WEE1 inhibitors.

P2, N=35, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

A combined regimen of MK-1775 and VK2 markedly decreased colony growth, disrupted mitochondrial membrane potential, and increased death in CML cells, including those resistant to TKIs. The results suggest that a combination of MK-1775 and VK2 represents a potentially effective treatment strategy for CML, especially in drug-resistant cases.

P2, N=60, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Aug 2025 --> Mar 2026 | Trial primary completion date: Aug 2025 --> Mar 2026

Here, we demonstrate that the WEE1 kinase inhibitor (WEE1i), Adavosertib, can sensitize the effect of G12Ci through the MYBL2-RRM2 axis, which is associated with poor prognosis in lung cancer...We also observed marked effects of the combination therapy in tumor xenografts models. Collectively, these results uncover the WEE1 kinase inhibitors, some of which are available clinically, as effective enhancers for G12Ci therapy.