Sarcopenia has gained considerable attention in the context of hepatocellular carcinoma, as it has been correlated with a poorer prognosis among patients undergoing sorafenib or lenvatinib treatment for hepatocellular carcinoma (HCC). The prognosis of patients with HCC and sarcopenia is significantly worse when treated with lenvatinib and PD-1 inhibitors. The combination regimen of lenvatinib plus PD-1 inhibitors should be cautiously recommended due to the inferior prognosis and higher AEs.

P2, N=30, Not yet recruiting, Harbin Medical University

P2, N=730, Recruiting, Merck Sharp & Dohme LLC | Trial completion date: Aug 2026 --> Mar 2027 | Trial primary completion date: Aug 2026 --> Mar 2027

Multikinase inhibitors sorafenib (Nexavar®) and lenvatinib (Lenvima®) have been used as first-line drugs with modest therapeutic effects. In addition, LASSBio-2052 significantly reduced CCNB1 and CCND1 expression in HCC cells. Our findings indicate that LASSBio-2052 is a promising prototype for further in vivo studies.

To gain further insights into the conformational dynamics of Mundulone and the reference FGFR1 inhibitor, Lenvatinib, we conducted time-evolution analyses employing 200 ns molecular dynamics simulations (MDS) and essential dynamics...Overall, the findings indicate that Mundulone exhibits promising binding affinity, specific interactions, and favorable drug profiles, making it a promising lead candidate. Further experimental analysis will be necessary to confirm its effectiveness and safety profiles for therapeutic advancement in the cancer field.Communicated by Ramaswamy H. Sarma.

Our findings indicate that both sorafenib and lenvatinib possess anticancer abilities by inducing the cytotoxicity of hepatocellular carcinoma cells. Furthermore, they show opposing effects on TGF-β-induced cell invasion and angiogenesis, thereby enhancing the understanding of the multifaceted functions of molecular targeted drugs in treating hepatocellular carcinoma.

This study showed that TACE/lenvatinib/PD-1 treatment was well tolerated with encouraging efficacy in patients with unresectable HCC. The patients with BCLC B-stage disease with early NLR response (decrease) and early AFP response (decrease > 20%) may achieve better clinical outcomes with this triple therapy.

P2, N=39, Recruiting, Tianjin Medical University Cancer Institute and Hospital

Lenvatinib, HAIC and PD-1 showed safe and promising anti-tumor activity compared with lenvatinib alone for HCC with high-risk features.

P2, N=20, Recruiting, Saint Petersburg State University, Russia

Only one-third of patients with advanced MSS/pMMR endometrial cancer exhibit a lasting response to the combination treatment of Pembrolizumab and Lenvatinib. The sensitivity and specificity of these biomarkers were 85.71% and 70.59%, and 85.71% and 85.71%, respectively. The proportion of CD20+ B lymphocytes and the CD8-to-CD20 lymphocytes ratio in the stroma of endometrial cancer serves as both a prognostic marker of response to immunotargeted therapy and a prognostic factor for progression-free survival in patients.

Genetic abnormalities with treatment options were found in 62.7% of advanced thyroid carcinomas. TP53 abnormality was an independent poor prognostic factor for overall survival in differentiated thyroid carcinoma. The time to treatment failure for lenvatinib was not different based on genetic profile.

P3, N=112, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Jul 2026 --> Mar 2025 | Trial primary completion date: Jul 2026 --> Aug 2023

P1, N=11, Active, not recruiting, Yousef Zakharia | Trial completion date: Sep 2024 --> Jun 2028

On the contrary, some patients with mucosal, acral or KIT-mutant melanoma may benefit from TKI-based therapies. Further studies focused on biomarker discovery and randomized trials are necessary to better understand the role of VEGFR1-3 as a therapeutic target in melanoma.

P2, N=300, Recruiting, Peking Union Medical College Hospital

P2, N=30, Not yet recruiting, Hui-Chuan Sun

P2, N=0, Withdrawn, ETOP IBCSG Partners Foundation | N=47 --> 0 | Not yet recruiting --> Withdrawn

P2, N=32, Active, not recruiting, Assistance Publique - Hôpitaux de Paris | Recruiting --> Active, not recruiting | N=50 --> 32 | Trial completion date: Feb 2025 --> Oct 2026 | Trial primary completion date: Apr 2024 --> Jul 2025

Our data show that nuclear KRT19 acts as a transcriptional co-repressor through promoting the deacetylase activity of the CoREST complex, resulting in dedifferentiation of liver cancer. These findings reveal a previously unrecognized function of KRT19 in directly shaping the epigenetic landscape in cancer.

Surgical intervention after lenvatinib treatment for advanced HCC was associated with longer PFS. Patients exhibiting decreased AFP levels or maintaining AFP levels within the normal limit may be suitable candidates for surgical intervention after lenvatinib treatment for advanced HCC.

P2, N=30, Recruiting, Peking Union Medical College Hospital | Not yet recruiting --> Recruiting

Pulrodemstat synergized with Lenvatinib based on suppression of PI3K-AKT signaling and activation of apoptotic signaling.

P=N/A, N=300, Recruiting, Sun Yat-sen University

Longitudinal tumor measurements over time were reasonably well defined by a tumor growth inhibition Emax model, which in addition to lenvatinib exposure, included model-predicted relative changes from baseline over time for Tie-2 and Ang-2 as having significant association with tumor response. The developed PK/PD models pave the way for dose optimization and potential prediction of clinical response.

P2, N=20, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Jan 2024 --> Jul 2024

P=N/A, N=135, Completed, Eisai Korea Inc. | Recruiting --> Completed | N=98 --> 135

P1, N=40, Recruiting, Chang Gung Memorial Hospital

P2, N=55, Completed, Peking University Cancer Hospital & Institute | Recruiting --> Completed | Trial completion date: May 2023 --> Mar 2024

P2, N=51, Active, not recruiting, National Cancer Center Hospital East | Recruiting --> Active, not recruiting

P1, N=10, Recruiting, Hadassah Medical Organization

The combination of pembrolizumab and lenvatinib did not show sufficient response in patients with NETs to warrant continued enrollment on trial.

P2, N=25, Not yet recruiting, Hyogo Medical University

P1/2, N=36, Recruiting, Chipscreen Biosciences, Ltd. | Phase classification: P1b/2 --> P1/2

P2, N=56, Not yet recruiting, Diwakar Davar | Trial completion date: Dec 2028 --> Jun 2029 | Initiation date: Jan 2024 --> May 2024 | Trial primary completion date: Dec 2026 --> Jun 2029

P2, N=10, Terminated, Massachusetts General Hospital | N=19 --> 10 | Trial completion date: Dec 2022 --> Jan 2024 | Recruiting --> Terminated | Trial primary completion date: Jun 2022 --> Jan 2024; Planned interim analysis

P2, N=43, Active, not recruiting, MedSIR | Recruiting --> Active, not recruiting

P2, N=30, Recruiting, University of Texas Southwestern Medical Center | Not yet recruiting --> Recruiting

P3, N=422, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Feb 2026 --> Sep 2024

P2, N=60, Recruiting, Mian XI | Not yet recruiting --> Recruiting

These findings suggested that HAND2-AS1 may be a potential therapeutic target and an indicator of early recurrence for HCC.

Sorafenib, lenvatinib, and cabozantinib are multikinase inhibitors approved for patients with metastatic RAI-refractory DTC, whereas vandetanib and cabozantinib are approved for patients with MTC. Management of thyroid carcinomas has evolved such that targeted therapies have become therapeutic options for patients with BRAF, RET, NTRK, ALK, and ROS1 alterations and even have reported efficacy in anaplastic thyroid carcinomas. In this article, we review the advances made over the years in the treatment of metastatic thyroid carcinoma and focus on the systemic therapies that have recently transformed the treatment landscape of advanced disease.