Lenvima (lenvatinib)

P2, N=47, Recruiting, Sun Yat-sen University | Not yet recruiting --> Recruiting

P2, N=28, Active, not recruiting, RenJi Hospital | Recruiting --> Active, not recruiting

FGFR4-high expression is associated with an immune-responsive phenotype in HCC and predicts inferior efficacy of lenvatinib plus PD-1 blockade.

What is already known on this topic:Pembrolizumab plus lenvatinib has been an emerging treatment for recurrent endometrial cancer, showing survival benefit in pMMR tumors. However, most data are from clinical trials with less heavily pretreated patients, and uncertainty remains about efficacy in platinum-resistant, p53-mutated, high-grade tumors and the optimal starting dose of lenvatinib given its toxicity.What this study adds:In a real-world cohort enriched for platinum-resistant, high-grade, p53-mutated, heavily pre-treated endometrial cancers, lenvatinib plus pembrolizumab achieved an objective response rate consistent with prior trials. A reduced starting dose of lenvatinib (≤10 mg) was non-inferior to higher doses, better tolerated, and associated with fewer dose reductions. Additionally, p53 mutation and good ECOG status predicted improved progression-free survival.How this study might affect research, practice or policy:These findings suggest that reduced-dose lenvatinib may maintain efficacy while improving tolerability in heavily pretreated high-grade tumors and platinum resistant, p53 mutated patients, supporting individualized dosing strategies. They also highlight p53 mutation as a potential predictive biomarker, warranting larger studies.

The protein expression profile of Bel7404-R cells were significantly different from those of the parental HCC cells. B4GALT4 was identified as a critical molecule for HCC resisting to lenvatinib, and B4GALT4 can be used as a new therapeutic target for lenvatinib-resistant liver cancer.

P2, N=75, Not yet recruiting, Jinling Hospital, China

Although causality cannot be established, these findings raise the hypothesis that PRES could be a class effect of angiogenesis inhibitors and call for ongoing epidemiological surveillance and timely multiprofessional management of hypertension as a risk-minimization strategy. The potential modulatory role of FGFR4 deserves further mechanistic translational studies.

Resistance to first-line multikinase inhibitors (MKIs) sorafenib and lenvatinib critically limits hepatocellular carcinoma (HCC) treatment efficacy. Crucially, PHF8 ablation reverses LMCD1-AS1-driven resistance, and in vivo xenografts confirm attenuated sorafenib efficacy with LMCD1-AS1 overexpression. Our work unveils the LMCD1-AS1/PHF8/H4K20me1 axis as a unified epigenetic-metabolic mechanism underlying MKI resistance, representing a promising therapeutic target and prognostic biomarker for HCC.

Two participants died of non-treatment-related AEs (acute kidney injury and unspecified death). Clinical trial registry: NCT02861573.

P1/2, N=50, Recruiting, Assistance Publique Hopitaux De Paris | Not yet recruiting --> Recruiting

We analyzed the effects of a combination of lenvatinib with the tetracycline-class antibiotics tigecycline and eravacycline in DTC cells with reduced response to lenvatinib and explored the underlying mechanism of action. Both combination therapies markedly impaired mitochondrial respiration, accompanied by down-regulation of anti-apoptotic Bcl-2 family members, activation of caspase-3/7, and cleavage of Poly (ADP-ribose) polymerase (PARP), which are hallmarks of apoptosis. Although limited to in vitro models and subject to pharmacological limitations, our findings provide a mechanistic proof-of-concept that mitochondria-targeting antibiotics may enhance lenvatinib responsiveness in a DTC cell line.

P1, N=17, Active, not recruiting, EMD Serono Research & Development Institute, Inc. | Trial completion date: Sep 2026 --> May 2026 | Trial primary completion date: Sep 2026 --> Feb 2026