Lenvima (lenvatinib)

P=N/A, N=150, Active, not recruiting, Peking University | Not yet recruiting --> Active, not recruiting | Trial completion date: Aug 2026 --> Jun 2027 | Trial primary completion date: Jun 2026 --> Dec 2026

This combination shows promising effects and good safety in patients with HCC who have received liver transplants. Such a method offers a fresh choice for treating those who are thought not to be suitable for immunotherapy, so it needs to be tested in more extensive controlled research.

P1/2, N=20, Recruiting, West China Hospital

Lenvatinib was interrupted, and intravenous piperacillin/tazobactam was administered; her symptoms improved without drainage. Lenvatinib was resumed at 8 mg with pembrolizumab, and no recurrence occurred. Early recognition and temporary interruption of lenvatinib with antibiotics may allow cautious rechallenge.

Lonafarnib effectively suppresses the malignant progression of anaplastic thyroid carcinoma both in ATC cell lines and in a BALB/c nude mouse xenograft model. The mechanism involves inhibition of Ras farnesylation and the downstream ERK signaling pathway, leading to activation of Caspase-3/PARP-mediated apoptosis and GSDME-mediated pyroptosis.

This study established the SERPINE2-JAK2/STAT3-NRF2-GCLC signaling axis as a key mechanism driving ferroptosis resistance and lenvatinib treatment failure. Targeting this axis provides a novel therapeutic strategy for overcoming lenvatinib resistance in HCC.

Lenvatinib-pembrolizumab did not improve OS compared with SOC. More participants discontinued lenvatinib-pembrolizumab and lenvatinib monotherapy than SOC. Further research is needed to determine effective second-line treatments for this population.

This review explores recent mechanisms by which aberrant nuclear β-catenin accumulation fosters resistance to frontline tyrosine kinase inhibitors like sorafenib and lenvatinib through ferroptosis evasion, cancer stemness, and β-catenin stabilization. Recent preclinical studies show that combining Wnt inhibitors with immunotherapy or tyrosine kinase inhibitors can reprogram the tumor microenvironment, restore ferroptosis sensitivity, eradicate cancer stem cells, enhance CD8+ T-cell infiltration, boost anti-tumor immunity, and overcome resistance with minimal side effects. Targeting the Wnt/β-catenin pathway offers a promising strategy to transform HCC treatment and improve outcomes by exploiting this pathway as a key therapeutic vulnerability.

The AUC for 6-, 12- and 18-month PFS rates were 0.663, 0.677 and 0.810 repetitively. The calibration curve showed that there was a good agreement between predicted progression probability and actual observation one, and DCA indicated a favorable clinical benefit of the nomogram. In summary, Aa practical and well-calibrated model was developed, which could objectively predict the prognosis of lenvatinib treatment in HCC patients.

Results from the RUBY and NRG-GY018 trials show that combining dostarlimab or pembrolizumab with platinum-based chemotherapy improves survival in patients with untreated advanced disease...Overcoming this resistance requires combination strategies, such as using anti-angiogenic agents like lenvatinib with immune checkpoint inhibitors, as shown in the KEYNOTE-775 trial...As molecular monitoring via liquid biopsy and the use of antibody-drug conjugates (ADCs) evolve, the personalization of immunotherapy continues to progress. This review examines current clinical evidence and the mechanisms of resistance to define the future of precision medicine in endometrial cancer.

P2, N=33, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: May 2026 --> May 2027 | Trial primary completion date: May 2026 --> May 2027

P3, N=404, Completed, BeOne Medicines | Active, not recruiting --> Completed