P1/2, N=856, Active, not recruiting, Loxo Oncology, Inc. | Recruiting --> Active, not recruiting

P2, N=13, Recruiting, Children's Hospital of Philadelphia | Not yet recruiting --> Recruiting | Initiation date: Nov 2024 --> Jul 2024

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

P2, N=68, Not yet recruiting, Harbin Medical University Cancer Hospital; Harbin Medical University Cancer Hospital

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

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

P2, N=36, Recruiting, The First Affiliated Hospital of Dalian Medical University; The First Affiliated Hospital of Dalian Medical University | Not yet recruiting --> Recruiting

P2, N=26, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Recruiting --> Active, not recruiting

The development of multi-kinase inhibitors cabonzantinib and vandetanib, and RET-targeted inhibitors selpercatinib, has completely changed the therapeutic arsenal for advanced disease, but their prescription is reserved to progressive disease with high tumor volume or to symptomatic disease inaccessible to local treatment in expert centers from the ENDOCAN-TUTHYREF network. Active surveillance is the alternative of choice for slowly progressing disease.

Activation of Nrf2 signaling by LR HCC cell-derived exosomal miR-301a-3p skewed the transformation of macrophages to the M2 phenotype. Our study provides new findings on the role of miR-301a-3p, suggesting it is a promising therapeutic target to improve HCC lenvatinib resistance.

The combination regimen demonstrated promising efficacy in treating unresectable HCC, accompanied by manageable safety profiles. Furthermore, the results of this investigation suggest that AFP holds promise as predictive biomarkers for this treatment strategy.

P2, N=38, Not yet recruiting, National Cancer Center, Japan

P2, N=30, Recruiting, University of Texas Southwestern Medical Center | Trial primary completion date: Aug 2024 --> Dec 2024

P2, N=39, Completed, Nanfang Hospital, Southern Medical University | Recruiting --> Completed

P2, N=58, Active, not recruiting, The Netherlands Cancer Institute | Trial completion date: Mar 2025 --> Mar 2026

This study encapsulates the research endeavors and treatment advancements of RET rearrangement solid tumors within the Chinese healthcare landscape, specifically highlighting the diverse real-world therapeutic approaches and their effectiveness in managing advanced RET rearrangement NSCLC among Chinese patients. Notably, targeted RET inhibitors like Pralsetinib have emerged as potent therapeutic agents, exhibiting remarkable efficacy and a manageable safety profile in this patient cohort. These findings underscore the potential of Pralsetinib and similar targeted therapies as novel treatment options for individuals with RET fusion-positive NSCLC.

BAIAP2L2 inhibits the levels of reactive oxygen species (ROS) by regulating GABPB1, thereby promoting cancer properties in HCC and reducing the sensitivity of HCC to lenvatinib. In summary, this study elucidates the role and underlying mechanism of BAIAP2L2 in HCC, providing a potential biomarker and therapeutic target for this disease.

The YAP-HER3 axis is crucial for the survival and adaptive resistance of high YAP-expressing RET-aberrant cancer cells treated with RET-TKIs. Combining YAP/HER3 inhibition with RET-TKIs represents a highly potent strategy for initial treatment.

P2, N=30, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

STM2457 treatment attenuated the serine synthesis pathway, induced oxidative stress, and sensitized HCC cells to sorafenib and lenvatinib treatments. In conclusion, our findings suggest that targeting m6A could be a potential therapeutic strategy for HCC treatment.

P3, N=1069, Active, not recruiting, Eisai Inc. | Trial completion date: Jul 2024 --> Mar 2026

P2, N=35, Not yet recruiting, University of Chicago

Compared to RT + S, RT + L had good efficacy in the treatment of hepatocellular carcinoma with PVTT. Validation is needed in prospective studies with larger sample sizes.

To date, this patient continues to show a near complete response to this treatment regimen. To our knowledge, this is the first documented case of SMARCB1-deficient RMC without hemoglobinopathy to receive this treatment regimen and show such a response.

BMI is a long-term predictor of the efficacy of lenvatinib plus camrelizumab, and obese/overweight patients have a better prognosis.

If, following downstaging, the patient qualifies for liver resection based on locally prevalent resectability criteria, then such therapy is labelled as conversion (from unresectable to resectable) therapy. In unresectable patients treated by a combination of treatment options, serological markers like neutrophil-to-lymphocyte ratio and alpha-fetoprotein are reported to predict treatment responses, thus enabling personalized medicine.

PDOs for drug sensitivity contribute to screening effective chemotherapy drugs for advanced pCCA, promoting conversion therapy and improving the prognosis.

Long-term treatment with selpercatinib is feasible. AEs are manageable with dose modifications, allowing most patients to continue safely on therapy.

Our findings suggest that Erastin or Lenvatinib can enhance the induction of ferroptosis in cholangiocarcinoma cells by photodynamic therapy by increasing intracellular ROS and inhibiting intracellular antioxidant pathways.

P3, N=480, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed

P=N/A, N=80, Recruiting, Tianjin Medical University Cancer Institute and Hospital | N=120 --> 80 | Trial primary completion date: Jan 2024 --> May 2024

G-Rh1 can regulate the immune microenvironment of HCC by targeting GR, thus increasing the antitumor effect of lenvatinib. Please cite this article as: Wang XH, Fu YL, Xu YN, Zhang PC, Zheng TX, Ling CQ, Feng YL. Ginsenoside Rh1 regulates the immune microenvironment of hepatocellular carcinoma via the glucocorticoid receptor. J Integr Med. 2024; Epub ahead of print.

Then we detected 6 repurposable drug molecules (Entrectinib, Imatinib, Ponatinib, Sorafenib, Retevmo, and Pazopanib) by molecular docking with KGs-mediated receptor proteins, ADME/T analysis, and cross-validation with the independent receptors. Therefore, these findings might be useful resources for wet lab researchers and clinicians to consider an effective treatment strategy against THCA.

Treatment with liposomes carrying siRNAs targeting IGF2BP3 or the glycolysis inhibitor 2-DG restored lenvatinib sensitivity in vivo. These findings highlight the connection between metabolic reprogramming and epigenetic regulation and suggest that targeting metabolic pathways may offer new strategies to overcome lenvatinib resistance in HCC.

In the absence of any prospective comparative study and to evaluate in a real-world context the clinical benefit of re-administering a PD-1 inhibitor (pembrolizumab 200 mg i.v. every 3 weeks, Q3W) with a multi-kinase inhibitor (lenvatinib, but at a reduced dose 10 mg p.o. daily due to its known toxicity) in this frail population of unmet need, we conducted here a retrospective comparison of LEAP-004-proposed combination with CC (carboplatin 4 AUC and dacarbazine 850 mg/m2 i.v. Q3W) in melanoma patients who relapsed to both checkpoint inhibitors, either in combinatorial or in sequential setting, between July 2022 and January 2024. Grade 3-5 treatment-related adverse events were documented in 48.7% (pembrolizumab/lenvatinib) and 75.6% (CC) of patients (p=0.034), which led to treatment discontinuation in 10.3% and 17.8% of cases, respectively. This is the first comparative study in patients with metastatic melanoma refractory to PD-1/CTLA-4 inhibition and showed significantly longer outcomes in cases treated with pembrolizumab/lenvatinib versus CC.

In REFLECT, lenvatinib was noninferior to sorafenib in terms of overall survival (OS) in patients with unresectable hepatocellular carcinoma (uHCC; median 13.6 vs. 12.3 months; HR 0.92, 95% CI 0.79-1.06). Responses were seen even in those patients with more severe disease at baseline. Tumor responses occurred early and were durable.

Transarterial chemoembolization combined with lenvatinib and PD-1 inhibitor (triple therapy) has displayed encouraging clinical outcomes for unresectable hepatocellular carcinoma (uHCC)...The presence of MPR or pCR could improve prognosis in patients with initially uHCC who underwent conversion surgery following triple therapy. The PR may become a surrogate marker for predicting the prognosis of these patients.

P2, N=30, Recruiting, Massachusetts General Hospital | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Mar 2024 --> Mar 2025

Multi-tyrosine kinase inhibitors such as sorafenib and lenvatinib are utilized for treating RAI-refractory FTCs. In addition, given that renin-angiotensin system (RAS) is the most common driver gene for FTC, it is also important to develop RAS inhibitors.

P=N/A, N=100, Recruiting, CHA University

P2, N=68, Not yet recruiting, Harbin Medical University