Stivarga (regorafenib)

P2, N=350, Recruiting, Fudan University | Not yet recruiting --> Recruiting

Clinically approved multikinase inhibitors-including ponatinib, gefitinib, and regorafenib-exhibit off-target RIPK2 inhibition, while selective compounds such as WEHI-345, GSK2983559, CSLP37, UH15-15, and thienopyrimidine derivatives represent key advances in selective blockade. Despite encouraging preclinical data, no RIPK2-specific inhibitor has yet achieved clinical approval due to safety and selectivity challenges. Continued structure-guided optimization, exploration of allosteric and degradation-based mechanisms, and integration into precision-medicine frameworks may ultimately enable safe and effective RIPK2-targeted therapies for inflammatory and autoimmune disorders, while the potential application in oncology remains under preclinical investigation.

For patients with high FLT1 expression, a combination therapy targeting this network-screened via molecular docking and dynamics simulations-may improve prognosis. This includes FLT1 inhibitors (Sorafenib, Regorafenib, Lenvatinib), supplemented by AKT1 inhibitors (Capivasertib) and VEGFA inhibitors (Bevacizumab) to suppress FLT1-associated malignant cell populations.

P=N/A, N=200, Completed, Sun Yat-sen University

P2, N=58, Not yet recruiting, Shanghai Zhongshan Hospital

Our predictive model may help identify patients at high risk of early mortality after regorafenib or trifluridine/tipiracil initiation and support shared decision-making between clinicians and patients regarding further chemotherapy or best supportive care.

Accordingly, combination approaches integrating regorafenib with targeted agents, immune checkpoint inhibitors (ICIs), metabolic modulators, or emerging therapeutic platforms are discussed. Overall, this review provides a systems-level understanding of regorafenib resistance and highlights the importance of mechanism-guided combination therapies and biomarker-driven strategies to improve clinical outcomes.

P2, N=110, Recruiting, Teclison Ltd. | Trial completion date: Dec 2025 --> Sep 2027 | Trial primary completion date: Dec 2025 --> Mar 2027

specifically, a CEA increase of <14.6% significantly predicts improved survival outcomes. These findings support the utility of serial marker monitoring in real-world practice, though prospective validation is warranted.

Clinical trial outcomes with axitinib plus avelumab differ significantly by ACC subtype. Furthermore, the identified 167-gene immune-related signature predicts clinical benefit to immunotherapy-based combinations in ACC. These findings provide a framework for future biomarker-driven trial design and patient stratification strategies for this rare malignancy.

This phase II clinical trial met its primary endpoint, demonstrating clinically meaningful antitumor activity and manageable toxicity with continuous daily REGO in advanced pretreated melanoma. The unprecedented high response rates in KIT-mutant melanoma and encouraging activity in BRAFV600-mutant patients receiving REGO + BRAF/MEKi support further investigation of REGO-based regimens in these subpopulations of melanoma patients.

P1/2, N=30, Completed, National Cancer Center Hospital East | Active, not recruiting --> Completed