Studies have shown that the clinical efficacy of the EGFR tyrosine kinase inhibitor gefitinib alone in treating HCC is limited...Among them, the best complex 6g exhibits significant antiproliferative activity against Huh7 cells and Huh7R (lenvatinib-resistant) cells...In addition, complex 6g causes a significant increase in the accumulation of reactive oxygen species (ROS), disrupts mitochondrial membrane potential (MMP), arrests the cell cycle in the G0/G1 phase, and induces apoptosis. Collectively, our findings demonstrate that complex 6g exhibits potential anti-HCC effects via dual-targeting of EGFR and TrxR.

P=N/A, N=32, Recruiting, Sun Yat-sen University

P2, N=28, Recruiting, RenJi Hospital | Trial completion date: Jul 2026 --> Oct 2026

Improvements in ORR and PFS for L+P versus sunitinib in aRCC were observed consistently across a range of biomarker subgroups defined using RCC driver mutations, PD-L1, gene expression signatures, and molecular subtypes.

Our study elucidated a previously unidentified mechanism of lenvatinib action and identified the RRP15-KBTBD8 axis as a novel therapeutic target in HCC, offering new avenues for treatment strategies in combating HCC.

P=N/A, N=146, Recruiting, Tianjin Medical University Cancer Institute and Hospital | N=80 --> 146

P3, N=252, Recruiting, Sun Yat-sen University

AXIN1-deficient patients have a lower response to lenvatinib, which may be associated with suppression of p15 mediated by WNT pathway activation. KDM5B inhibitors can restore p15 levels, resulting in efficient killing of resistant cells in HCC.

P3, N=184, Completed, Chipscreen Biosciences, Ltd. | Recruiting --> Completed | Trial completion date: Dec 2025 --> Apr 2024 | Trial primary completion date: Dec 2024 --> Apr 2024

P2, N=51, Active, not recruiting, Institut Curie | Recruiting --> Active, not recruiting | Trial completion date: Sep 2028 --> Nov 2026 | Trial primary completion date: Jan 2027 --> May 2025

P2, N=60, Recruiting, University College, London | Trial completion date: Jul 2026 --> Jul 2030 | Trial primary completion date: Jul 2026 --> Jul 2028

P=N/A, N=50, Recruiting, Regina Elena Cancer Institute | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Jul 2024 --> Dec 2024

P2, N=6, Active, not recruiting, Providence Health & Services | Recruiting --> Active, not recruiting | N=30 --> 6 | Trial primary completion date: Jun 2025 --> Dec 2024

P1/2, N=0, Withdrawn, Tel Aviv Medical Center | N=47 --> 0 | Not yet recruiting --> Withdrawn

Considering the great difficulty in establishing AM cell culture lines, these findings suggest that AM may be more sensitive to microenvironment perturbations than CM. In conclusion, dual FGFR/VEGFR inhibition may be a viable therapeutic strategy that targets the unique biology of AM.

The predictive performance of the combined model established by integrating ultrasomics features and clinical baseline characteristics was improved, with the AUC, sensitivity, specificity, and accuracy of the RF machine learning combined model for the training and test dataset reaching 0.937 (95%CI, 0.884-0.971), 0.822 (95%CI, 0.702-0.909); 0.857, 0.833; 0.857, 0.800; 0.857, 0.817, respectively. To predict the status of EGFR expression in HCC patients, the ultrasomics model and combined model created by five machine learning algorithms can be utilized as efficient and noninvasive techniques, and the ultrasomics model and combined model established by RF classifier have the best predictive performance.

Our findings revealed that triple therapy is an effective, well-tolerated regimen for HCC patients with EM. AFP level and NLR are prognostic risk factors for triple therapy in this patient population.

P3, N=180, Recruiting, Chipscreen Biosciences, Ltd. | Trial completion date: Dec 2024 --> Dec 2025

P3, N=131, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed

P3, N=674, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed

Although these Kampo medicines are reported to inhibit drug-metabolizing enzymes and drug transporters, the risk of drug interactions for patients receiving lenvatinib therapy is low. Patients should feel confident that they can receive Kampo medicines as supportive care for lenvatinib therapy without a risk of drug interactions that could affect treatment efficacy.

In conclusion, HBV infection increases resistance to both sorafenib and lenvatinib in hepatoma cells by influencing the cell cycle regulatory genes and critical signaling pathways. However, the resistance mechanisms likely differ between the two medications.

P2, N=11, Active, not recruiting, Washington University School of Medicine | Trial completion date: Feb 2027 --> Dec 2025 | Trial primary completion date: Jul 2025 --> Jul 2024

Our study revealed that lenvatinib-induced NETs inhibited the cuproptosis of HCC cells, suggesting that targeting the IL33/PADI4/NET axis represents a promising therapeutic strategy for ameliorating lenvatinib resistance in HCC.

P1/2, N=30, Active, not recruiting, National Taiwan University Hospital | Trial completion date: Jun 2023 --> Dec 2024

In intermediate-to-advanced HCC, the BeSiIT and LeSiIT groups exhibited acceptable toxicities and comparable PFS, OS, and ORR.

We have first shown that doxorubizen has a potent antineoplastic effect in vitro in 8305C and in 5 different pATC, and that can synergize with lenvatinib. These results open the way to a future evaluation of the antineoplastic effect of doxorubizen in ATC patients.

P2, N=33, Recruiting, The First Affiliated Hospital with Nanjing Medical University | Initiation date: Mar 2024 --> Dec 2023

P2, N=9, Terminated, Chipscreen Biosciences, Ltd. | N=38 --> 9 | Recruiting --> Terminated; During the enrollment period of this project, due to the increasing proportion of patients receiving capecitabine adjuvant therapy and the large number of trials competing for the same number of lines in various centers

The ORR of intrahepatic lesions by CRAFITY 0, 1 and 2 were 37.9%, 35%, 30.6% (p= .688). CRAFITY score is a good predictor of prognosis in HCC patients receiving Len-P.

P2, N=408, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Feb 2027 --> Dec 2025

Based on these findings, the patient was diagnosed with stage IIIC2 endometrial cancer (pT1bN2M0, clear cell carcinoma) and received postoperative adjuvant therapy with paclitaxel and carboplatin. Five cycles of pembrolizumab and lenvatinib followed by four cycles of doxorubicin and cisplatin were ineffective. The patient died 13 months after the diagnosis of recurrence.

The HCC circRNA/miRNA/mRNA network provides new insights into the post-transcriptional regulatory mechanism of HCC. The hsa_circ_0001726/miR-140-3p/KRAS axis is involved in HCC progression and lenvatinib resistance.

Collectively, GFPT2 is potentially useful as a biomarker for prognostic prediction and immune infiltration in a variety of malignancies ,and could lead to exciting new approaches to personalized oncotherapy.

Transcriptomic analysis of these resistant organoids identified key pathways related to KRAS signaling, inflammation, and epithelial-mesenchymal transition (EMT), revealing potential targets for overcoming Lenvatinib resistance. This study provides valuable insights into MASH-related HCC progression and drug resistance, offering a model for further therapeutic research.

P2, N=43, Active, not recruiting, National Cancer Center Hospital East | Recruiting --> Active, not recruiting | Trial primary completion date: Aug 2025 --> Aug 2026

P2, N=603, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed

Our findings suggest lenvatinib is a valuable treatment option for patients with HCC recurrence after LT.

P3, N=328, Not yet recruiting, Affiliated Hospital of Guangdong Medical University; Affiliated Hospital of Guangdong Medical University

P2, N=38, Recruiting, Fudan University Shanghai Cancer Center; Fudan University Shanghai Cancer Center

P2, N=46, Not yet recruiting, Cancer Hospital, Chinese Academy of Medical Sciences; Cancer Hospital, Chinese Academy of Medical Sciences

P2, N=30, Not yet recruiting, The First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital); The First Affiliated Hospital of Nanjing Medical University