Lenvima (lenvatinib) / Eisai, Merck (MSD), Knight Therap - LARVOL DELTA

Tolerability and Treatment Duration of Recommended vs Reduced Starting Doses of Vascular Endothelial Growth Factor (VEGF) Tyrosine Kinase Inhibitors (TKI) in Patients with Renal Cell Carcinoma (RCC) (HOPA 2026) - "Eligible patients include adults (≥18 years) with metastatic ccRCC who initiated therapy with cabozantinib, lenvatinib, or axitinib between January 1, 2017, and December 31, 2024...Exclusion criteria include patients participating in a clinical trial, receiving of sunitinib, pazopanib, or Cometriq formulations, and filling at outside pharmacies or through patient assistance programs... Results Pending"

Clinical • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Comparative Safety and Tolerability of Tyrosine Kinase Inhibitor and Immunotherapy Combination Therapies for Clear Cell Renal Cell Carcinoma: A Retrospective Review (HOPA 2026) - "This will be a retrospective chart review of patients between 18 and 89 years old diagnosed with ccRCC who initiated treatment with axitinib/pembrolizumab, lenvatinib/pembrolizumab, or cabozantinib/nivolumab at AHN between August 1, 2021 and August 31, 2025... Pending results and data analysis."

Combination therapy • Retrospective data • Review • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Characterizing hypertension and its management in patients receiving lenvatinib (HOPA 2026) - "Outcomes will be stratified by treatment completeness (completion or AE-related discontinuation) and indication (renal cell carcinoma, hepatocellular carcinoma, differentiated thyroid cancer, or other). Results*, Conclusions* *Pending – data collection completion by 3/1/2026"

Clinical • Cardiovascular • Genito-urinary Cancer • Hepatocellular Cancer • Hypertension • Myocardial Infarction • Renal Cell Carcinoma • Solid Tumor • Thyroid Gland Carcinoma

ACTION-I: TACE or Ablation Combined With Sintilimab and Ipilimumab N01 as Neoadjuvant Therapy for Resectable Hepatocellular Carcinoma With Intermediate-High Recurrence Risk (clinicaltrials.gov) - P2 | N=90 | Not yet recruiting | Sponsor: Sun Yat-sen University

New P2 trial • Hepatocellular Cancer • Oncology • Solid Tumor

Treatment with Kinase Inhibitors Plus Myo-Inositol as Re-Differentiating Agents in Iodine-Refractory Thyroid Cancers. (PubMed, Life (Basel)) - "MI may have a synergistic effect at the cellular level, and the possible increase in the re-differentiation of RAIR-TC in patients treated with KIs plus MI may have great clinical relevance. The re-uptake of RAI will be evaluated as the primary endpoint, and Tg values and QoL will be evaluated as the secondary endpoints. The main limitation of this study is that we do not investigate any clinical effects. We will have to postpone the clinical analysis to a later date after the administration of RAI for therapeutic purposes."

Journal • Oncology • Solid Tumor • Thyroid Gland Carcinoma

Antitumor and antiangiogenic activities of E7386 in combination with lenvatinib in human endometrial carcinoma xenograft models (AACR 2026) - P1/2 | "These results suggest that the combination of E7386 with LEN exerted enhanced antiangiogenic activity against tumor microvessels compared with LEN-alone, and demonstrated potent antitumor activity in preclinical EC xenograft models."

Combination therapy • Preclinical • Endometrial Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CREBBP • CTNNB1 • PECAM1

Analytical accuracy and clinical performance of the OncoMate MSI Dx Analysis System in a subset of KEYNOTE-775 endometrial carcinoma classified as MSS (not MSI-H) by the companion diagnostic (AACR 2026) - "The OncoMate® MSI Dx assay was accurate compared with an established IHC orthogonal method and provided complementary information to IHC about tumor MMR status for some patients. The assay, which directly assesses DNA MMR function via microsatellites, retrospectively identified EC patients who would benefit from combination treatment with pembrolizumab plus lenvatinib compared with TPC. Specifically, pembrolizumab plus lenvatinib efficacy in a subset of KEYNOTE-775 participants with CDx-defined MSS (not MSI-H) tumors was comparable to the efficacy observed in all IHC-defined pMMR participants randomized in the original trial."

Clinical • Companion diagnostic • MSI-H • MSi-H Companion diagnostic • PD(L)-1 companion diagnostic • Endometrial Cancer • Microsatellite Instability • Oncology • Solid Tumor • MSI

Genome-wide CRISPR-Cas9 screen identifies genes conferring lenvatinib resistance in hepatocellular carcinoma (AACR 2026) - "Background: Tyrosine kinase inhibitors (TKIs), such as lenvatinib, sorafenib, and regorafenib, form a key component of current systemic therapy for advanced hepatocellular carcinoma (HCC). Our findings demonstrate that, even when proliferation appears unchanged, TKI exposure imposes a metabolic stress that drives a rewiring of nucleotide biosynthesis and a pronounced dependency on Molecule A. This adaptive shift is observed across distinct TKIs and cancer types, indicating that altered nucleotide metabolism represents a broadly conserved mechanism of drug resistance. Because clinically approved inhibitors of Molecule A are already available, these results provide a strong rationale for therapeutic repositioning strategies aimed at overcoming TKI resistance in hepatocellular carcinoma."

Hepatocellular Cancer • Oncology • Solid Tumor • MYBL2 • PCIF1

Evaluating the molecular mechanism of axitinib response in head and neck squamous cell carcinoma (AACR 2026) - "Further, when testing the mechanism, we observed that axitinib, but not Lenvatinib (known VEGFR inhibitor), induced apoptosis in HNSCC cell lines. Future studies will allow us to continue investigating axitinib's mechanism of action and its therapeutic potential in PI3K aberrant HNSCC. Our findings support clinical advancement of axitinib and use of PI3K genetic status as a predictive marker for therapeutic response for a large subset of HNSCC patients with limited therapeutic options."

IO biomarker • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PIK3CA • PTEN

Combination of the GCN2 activator HC-7366 with VEGFR-TKI results in greater efficacy than VEGFR-TKI alone or VEGFR-TKI/HIF-2i combinations in ccRCC (AACR 2026) - P1 | "HC-7366 alone achieved 63% tumor growth inhibition (TGI), whereas cabozantinib alone induced 30% regression (1/8 PR) and lenvatinib alone produced 95% TGI...Furthermore, in a single mouse trial of 10 RCC PDX models, addition of HC-7366 to axitinib improved outcomes in 8/10 PDX models and was superior to the belzutifan/axitinib doublet in multiple models...A phase 1b clinical trial is now ongoing to evaluate the safety, tolerability, and efficacy of both HC-7366/belzutifan and HC-7366/cabozantinib doublets in metastatic ccRCC (NCT06234605). These results will form a foundation for future evaluation of triplet combinations that integrate HC-7366, VEGFR-TKIs, and HIF-2 inhibitors."

Clinical • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • EPAS1 • HIF1A

Elucidation of breakage-fusion-bridge (BFB)-mediated EGFR amplification in lenvatinib-resistant hepatocellular carcinoma (AACR 2026) - "Combined treatment with lenvatinib and erlotinib, an EGFR inhibitor, reduced viability and restored sensitivity. In conclusion, our findings suggest BFB-driven EGFR amplification as a key structural and functional driver of lenvatinib resistance in HCC. Lenvatinib combined with an EGFR inhibitor may offer a treatment option for patients with HCC exhibiting elevated EGFR expression."

IO biomarker • Hepatocellular Cancer • Oncology • Solid Tumor • EGFR • FGFR • PAK2

Multitarget kinase inhibitor olverembatinib (HQP1351) is efficacious and synergizes with chemotherapy in preclinical models of endometrial carcinoma (EC) (AACR 2026) - "Olverembatinib was significantly more potent (IC50 up to 100-fold lower) than lenvatinib in cell growth inhibition in AN3CA, HEC-1B, RL95-2, and Ishikawa cells...Combining paclitaxel (10 mg/kg) and carboplatin (50 mg/kg) with olverembatinib (10 mg/kg) significantly enhanced the latter's antitumor activity, with a T/C value of 9.08% and synergistic index of 1.37... In a broad range of preclinical in vitro and in vivo EC models, olverembatinib is efficacious and synergizes with chemotherapy to promote antitumor effects. The findings support future clinical evaluation of olverembatinib and its combination with other approved treatment options in EC."

Preclinical • Endometrial Cancer • Oncology • Solid Tumor • Uterine Cancer • CASP3 • CDK4 • CDK6 • FGFR2 • FLT1 • STAT3

EZH2-AR non-canonical axis activation in TKI-resistant RCC: Differential effects of lenvatinib and cabozantinib (AACR 2026) - "Consistently, AR expression is observed in RCC lines resistant to sunitinib, dovitinib, and lenvatinib, but not with cabozantinib treatment...Overall, our findings suggest that EZH2-dependent kinase reprogramming drives AR phosphorylation and activation, contributing to drug resistance to selective TKIs. Cabozantinibunique ability to bypass AR/EZH2 upregulation underscores the need to explore alternative resistance pathways."

Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • AR • EZH2

Molecular Profile of Advanced Radioiodine-refractory Thyroid Cancer and Response to Lenvatinib Treatment. (PubMed, J Clin Endocrinol Metab) - "The RAIR-TC molecular profile is heterogeneous with TERT being the most frequent mutation. Cases negative for all mutations and cases presenting the coexistence of TERT + driver mutation had a worse response to lenvatinib. Conversely, the presence of 1 driver mutation correlated with a better response to lenvatinib."

Journal • Oncology • Solid Tumor • Thyroid Gland Carcinoma • BRAF • RAS • TERT • TP53

Targeting G6PD (Glucose-6-Phosphate Dehydrogenase) as a Biomarker of Therapeutic Vulnerability in Renal Cell Carcinoma. (PubMed, Int J Mol Sci) - "A high gene expression was observed in lenvatinib non-responder cell lines, and DepMap dose-response curves indicated modest responses to VEGF inhibitors. In vitro, ACHN was more sensitive to VEGF inhibition, particularly cabozantinib, whereas G6PDi-1 had stronger effects in 786-O, impairing viability, migration, and clonogenic capacity. Our findings support G6PD as a biomarker of tumor aggressiveness and G6PDi-1 as a potential therapeutic in RCC models."

Biomarker • IO biomarker • Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • G6PD • PRCC

Efficacy of Lenvatinib as Second-Line Therapy After Atezolizumab Plus Bevacizumab for Hepatocellular Carcinoma. (PubMed, Curr Oncol) - " Lenvatinib as second-line therapy after ATZ/BEV was associated with improved survival in unresectable HCC. Preservation of liver function and the ability to maintain adequate lenvatinib exposure were associated with favorable outcomes, likely reflecting baseline prognosis and treatment feasibility rather than lenvatinib-specific predictive factors."

Journal • Retrospective data • Hepatocellular Cancer • Oncology • Solid Tumor

Lenvatinib-Induced Acalculous Cholecystitis-An Often-Unrecognized Toxicity: A Case Series and Literature Review. (PubMed, Curr Oncol) - "This review provides evidence that Lenvatinib-induced acalculous cholecystitis is not as rare as initially thought from the Lenvatinib licensing studies; hence, this is an adverse event that merits more attention. Oncologists using Lenvatinib should be aware of this potential toxicity and be familiar with its management."

Journal • Review • Endometrial Cancer • Gastroenterology • Hepatocellular Cancer • Hepatology • Oncology • Pain • Renal Cell Carcinoma • Solid Tumor • Thyroid Gland Carcinoma

Efficacy and Safety of Envafolimab Combined With Capecitabine and Lenvatinib as Postoperative Adjuvant Therapy in Resected Biliary Tract Cancer With High-Risk Recurrence Factors: A Phase II Single-Center Prospective Study. (PubMed, Cancer Med) - "The adjuvant combination of envafolimab, lenvatinib, and capecitabine demonstrates promising efficacy and a manageable safety profile in high-risk BTC patients after R0 resection. However, these findings still require validation in larger, multicenter, randomized controlled trials."

Journal • P2 data • Biliary Cancer • Biliary Tract Cancer • Oncology • Solid Tumor • CA 19-9

A patient-derived fragmented tumor assay for detailed evaluation of drug response in the tumor microenvironment (TME) using scRNAseq (AACR 2026) - "To determine how therapies broadly affect the TME, we treated samples with either the multikinase inhibitor, Lenvatinib, immune checkpoint inhibitors (ICIs) Pembrolizumab/Nivolumab, or STING agonist cGAMP. Endothelial cells of the tumor vasculature are one of the most difficult TME cell components to evaluate by conventional bulk analysis methods. Our results demonstrate that TME-dependent cell-specific responses to drug exposure are observable by combining tumor fragmentation and scRNAseq. This allows the platform to be used for the characterization of responses to new investigational agents, particularly those that target the non-tumor cell components of the TME, evaluate mechanism of action in detail, and assess the promise of such agents for treating solid tumor malignancies."

Clinical • IO biomarker • Tumor microenvironment • Endometrial Cancer • Oncology • Solid Tumor • IFNG

Noninvasive artificial intelligence system for prediction of lenvatinib based therapeutic regimens response and outcome in unresectable hepatocellular carcinoma (AACR 2026) - "The integration of deep learning radiomics and tumor phenotypic features in VALIANT models significantly enhances treatment response prediction for lenvatinib-based therapy in uHCC. This clinically applicable AI system enables comparative assessment of four lenvatinib-based regimens, facilitating personalized therapeutic selection and potentially improving patient outcomes through precision medicine approaches."

Non-invasive • Hepatocellular Cancer • Oncology • Solid Tumor

Beyond hydrolase: Lactylation converts ABHD6 into a mitochondrial regulator of lenvatinib resistance in HCC (AACR 2026) - "Abstract is embargoed at this time."

Late-breaking abstract • Hepatocellular Cancer • Oncology

Harnessing NOPE: A key oncofetal protein driving β-catenin signaling through peptidic antigen receptor macrophages in hepatocellular carcinoma (AACR 2026) - "In MHCC-97L cells, NOPE overexpression enhanced T-IC features, including self-renewal, tumorigenicity, cell invasiveness, expression of liver T-IC markers, and resistance to lenvatinib treatment...The NOPE/PABPC1 complex regulates cell state and drug resistance by directly affecting the β-catenin signaling pathway, potentially through its impact on YB-1 mRNA stability. We identified NOPE as a functional oncofetal protein that promotes liver cancer stemness by activating the β-catenin signaling pathway, which can be targeted by a novel pCAR-Ms approach."

Embryonal Tumor • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • GPC3 • PABPC1

Developing an ascitic fluid-derived organoid model for transcriptomic and therapeutic investigations in ovarian cancer (AACR 2026) - "The comprehensive characterization of ascites-derived organoids at histological, protein marker, and transcriptomic levels, along with systematic drug sensitivity comparisons across multiple experimental platforms, will significantly enhance their clinical and translational relevance."

Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • PAX8

Targeting HCC tumor microenvironment interactions using an advanced HCC patient-derived on-chip model (AACR 2026) - "The screen revealed that SoC drugs sorafenib and lenvatinib reduced culture viability and induced profound changes in vascular bed organization, while atorvastatin decreased viability without affecting vascular structures...Tocilizumab, galunisertib, and vactosertib lowered IL6 levels, whereas halofuginone increased IL6. These findings highlight the utility of the PDChip model in visualizing drug-induced responses at both molecular and morphological levels, providing detailed insights into drug effects on specific cellular compartments within the HCC TME. This platform enabled a detailed evaluation of drug-induced responses in the tumor and associated microenvironment, highlighting their importance in preclinical research for understanding diseases and developing new drugs."

Biomarker • Clinical • Metastases • Tumor microenvironment • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • IL6

β-Hydroxybutyrate-mediated lysine butyrylation determines therapy response in liver cancer (AACR 2026) - "Combination treatment of lenvatinib and ketogenic diet which induces BHB level could drastically attenuate tumor development in mice bearing tumors. This study presents a potentially translatable combination treatment strategy to potentiate the therapeutic efficacy of lenvatinib in advanced HCC."

Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor