- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), Lenvima (lenvatinib) / Eisai, Merck (MSD)
Enrollment change, Trial completion date, Trial termination, Trial primary completion date: Pembrolizumab And Lenvatinib In Leptomeningeal Metastases (clinicaltrials.gov) - Mar 14, 2024
P2, N=10, Terminated,
N=19 --> 10 | Trial completion date: Dec 2022 --> Jan 2024 | Recruiting --> Terminated | Trial primary completion date: Jun 2022 --> Jan 2024; Planned interim analysis
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), Lenvima (lenvatinib) / Eisai, Merck (MSD)
Enrollment closed: PECATI: Combination of Pembrolizumab and Lenvatinib, in Pre-treated Thymic CArcinoma paTIents (clinicaltrials.gov) - Mar 13, 2024
P2, N=43, Active, not recruiting,
Our study suggests that residual liver function and subsequent salvage treatments are major determinants of clinical outcomes in patients treated with AB and lenvatinib; these factors should be considered in future comparative studies. Recruiting --> Active, not recruiting
- |||||||||| Enrollment closed, Metastases: MK-6482-012 China Extension: A Study of Pembrolizumab (MK-3475) in Combination With Belzutifan (MK-6482) and Lenvatinib (MK-7902), or Pembrolizumab/Quavonlimab (MK-1308A) in Combination With Lenvatinib, vs Pembrolizumab and Lenvatinib, for Treatment of Advanced Clear Cell Renal Cell Carcinoma (MK-6482-012)-China Extension Study (clinicaltrials.gov) - Mar 12, 2024
P3, N=249, Active, not recruiting,
Not yet recruiting --> Recruiting Recruiting --> Active, not recruiting
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD)
Journal: Cost sharing for oral lenvatinib among commercially insured patients. (Pubmed Central) - Mar 12, 2024
Health systems and drug manufacturers must identify patients with high out-of-pocket costs and provide convenient access to financial assistance programs so that patients are not forced to forgo the benefits of these drugs due to financial barriers. Value-based payment models and drug pricing reform are also needed to address underlying drivers of high drug costs.
- |||||||||| Enrollment closed, Metastases: A Study of Pembrolizumab (MK-3475) in Combination With Belzutifan (MK-6482) and Lenvatinib (MK-7902), or Pembrolizumab/Quavonlimab (MK-1308A) in Combination With Lenvatinib, Versus Pembrolizumab and Lenvatinib, for Treatment of Advanced Clear Cell Renal Cell Carcinoma (MK-6482-012) (clinicaltrials.gov) - Mar 12, 2024
P3, N=1653, Active, not recruiting,
Lenvatinib dose modifications at the physician's discretion, considering the balance between effectiveness and safety, may contribute to the long-term treatment. Recruiting --> Active, not recruiting
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), Lenvima (lenvatinib) / Eisai, Merck (MSD)
Single Port Supine Bilateral Adrenalectomy (Video Abstract Theater) - Mar 12, 2024 - Abstract #AUA2024AUA_3474;
Adjuvant lenvatinib and pembrolizumab immunotherapy were administered due to progression free survival (PFS) benefit demonstrated in the CLEAR trial. The SP robotic platform with its low profile and flexible positioning can allow surgeons to perform bilateral surgical procedures, such as adrenalectomy without the need for patient repositioning and removing the need for multiple peritoneal entry sites.
- |||||||||| Stivarga (regorafenib) / Bayer, Lenvima (lenvatinib) / Eisai, Merck (MSD), Cabometyx (cabozantinib tablet) / Exelixis, Ipsen
Discovery of a new class of aryl-thiazoline sulfonamides as CDK4/6 inhibitors targeting hepatocellular carcinoma (Virtual; Virtual Session (Virtual Only)) - Mar 12, 2024 - Abstract #ACSSp2024ACS_Sp_11462;
Current chemotherapeutic options available for systemic treatment include sorafenid, lenvatinib, regorafenib, and cabozantinib, which are tyrosine kinase inhibitors...These results provide a framework for further optimization of the chemical structure and elaborate biochemical studies to understand the mechanism of cell death better. We also plan to synthesize a series of PROTACs using these newly discovered CDK4/6 targeting molecules and investigate their biological activity.
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), Lenvima (lenvatinib) / Eisai, Merck (MSD)
Journal: Management of Adverse Reactions Related to Lenvatinib Plus Pembrolizumab Treatment Among Patients With Renal Cell Carcinoma. (Pubmed Central) - Mar 11, 2024
Adverse reactions can generally be managed by: (1) advising the patient on precautionary measures (eg, for stomatitis, practice dental hygiene, avoid irritating foods, and maintain adequate hydration), (2) monitoring for changes in symptoms from baseline (eg, changes in bowel movements, blood pressure or level of fatigue), (3) interrupting/dose reducing lenvatinib or interrupting pembrolizumab, if warranted, and advising the patient to manage their current symptoms via self-care (managing diarrhea with antidiarrheal agents and hydration), and (4) implementing medical interventions (eg, thyroid replacement or antihypertensive therapy) when needed. Through successful management of adverse reactions, oncology clinicians can improve the well-being of their patients and likely enhance adherence rates to treatment with lenvatinib and pembrolizumab.
- |||||||||| Journal, HEOR, Combination therapy, Cost-effectiveness, Cost effectiveness: Cost effectiveness of immunotherapy combination therapies for endometrial cancer. (Pubmed Central) - Mar 7, 2024
We focused on approvals for endometrial cancer, and conducted a cost-effectiveness analysis for combination options approved in treating recurrent or advanced endometrial cancer (i.e. pembrolizumab plus lenvatinib versus placebo; dostarlimab plus chemotherapy versus placebo), and found neither regimen was cost-effective at a willingness-to-pay of $100,000 per Equal Value of Life Years Gained (evLYG). While these costs may not necessarily be translated to an individual patient, these costs are absorbed by healthcare systems and insurance providers on a larger scale with downstream effects on individuals contributing to healthcare costs a whole.
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD)
Enrollment closed, Trial completion date, Trial primary completion date, Metastases: STELLAR: A Study to Evaluate the Safety and Tolerability of Lenvatinib in Participants With Advanced or Unresectable Hepatocellular Carcinoma (clinicaltrials.gov) - Mar 7, 2024
P=N/A, N=1000, Active, not recruiting,
While these costs may not necessarily be translated to an individual patient, these costs are absorbed by healthcare systems and insurance providers on a larger scale with downstream effects on individuals contributing to healthcare costs a whole. Recruiting --> Active, not recruiting | Trial completion date: Mar 2028 --> Mar 2031 | Trial primary completion date: Mar 2028 --> Mar 2031
- |||||||||| AlloStim (bioengineered allogeneic immune cells) / Immunovative
Enrollment open, Metastases: ALIVE: Immunotherapy for Advanced Liver Cancer (clinicaltrials.gov) - Mar 6, 2024
P2/3, N=150, Recruiting,
Recruiting --> Active, not recruiting | Trial completion date: Mar 2028 --> Mar 2031 | Trial primary completion date: Mar 2028 --> Mar 2031 Not yet recruiting --> Recruiting
- |||||||||| Multivariate analysis of ex vivo kidney 3D immune-microtumors for functional precision medicine (Section 6) - Mar 5, 2024 - Abstract #AACR2024AACR_9713;
P
3D immune-microtumors were treated with FDA-approved regimens including immunotherapies (ipilimumab, nivolumab, pembrolizumab) and receptor-tyrosine kinase inhibitors (TKIs)(cabozantinib, lenvatinib, axitinib) as monotherapies or combination therapies...Population analyses revealed intra-patient response heterogeneity (N=7).In conclusion, we showed MoA-agnostic, patient-dependent responses to FDA-approved clinical treatment regimens via molecular and functional spatio-temporal analyses. Clinical outcome correlation is currently underway in our advanced RCC study PEAR-TREE2 as well as in breast NCT05435352 and brain NCT06038760 tumors.
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD)
Therapeutic potential of ketogenic diet as an adjuvant to lenvatinib treatment in hepatocellular carcinoma (Section 44) - Mar 5, 2024 - Abstract #AACR2024AACR_9227;
Combination treatment of lenvatinib and ketogenic diet which induces BHB level could drastically attenuate tumor development in immunocompetent mice bearing hepatic tumors. This study presents a potentially translatable combination treatment regimen to potentiate the therapeutic efficacy of lenvatinib in advanced HCC.
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD), Rubraca (rucaparib) / Pharma& Schweiz
Identification of serine/threonine kinase 39 (STK39) as a driver for multidrug resistance in hepatocellular carcinoma (Section 8) - Mar 5, 2024 - Abstract #AACR2024AACR_8628;
Additionally, STK39 plays a critical role in regulating PARP1-mediated chromatin decondensation, which enables it to open chromatin structure at the promoter regions of SOX2/OCT4. In summary, treatment of molecular targeted drugs including rucaparib and lenvatinib with STK39 inhibitor may be a potential therapeutic strategy for treatment of this deadly disease.
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD)
TESC mediates resistance to lenvatinib in hepatocellular carcinoma by regulating cell autophagy (Section 24) - Mar 5, 2024 - Abstract #AACR2024AACR_8051;
Preclinical data and preliminary human imaging demonstrate the potential of the novel binder as a theranostic agent for the treatment of patients with GPC3+ HCC. TESC expression levels are associated with the sensitivity of liver cancer cells to lenvatinib, possibly by inhibiting autophagy and affecting the sensitivity of liver cancer cells to lenvatinib.
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD)
Lenvatinib as a potential treatment option for invasive mucinous lung adenocarcinoma (Section 46) - Mar 5, 2024 - Abstract #AACR2024AACR_7814;
P=N/A
We report two cases of metastatic RET fusion-negative mucinous lung adenocarcinoma, in which treatment with the multitargeted TKI Lenvatinib led to significant clinical improvement. Biological rationale to explain the effect of lenvatinib in invasive mucinous lung adenocarcinoma needs to be explored.
- |||||||||| NCE 401 / Tium Bio, Chiesi
TU2218 (TGF?RI/VEGFR2 dual inhibitor) maximizes the benefit of cancer immunotherapies (Section 3) - Mar 5, 2024 - Abstract #AACR2024AACR_6912;
In the 4T1 of TNBC type, a level of tumor reduction was significant to p<0.001 on TU2218 and anti-PD-1 antibody combination group compared to vehicle, whereas anti-PD-1 antibody alone or anti-PD-1 antibody and paclitaxel combination group was not significant...In CT26, the efficacy of Lenvatinib and anti-PD-1 antibody combination therapy was compared with the combination of Lenvatinib, anti-PD-1 antibody, and TU2218...Moreover, a statistical difference in anti-tumor activity between the two groups was significant at p<0.001. Collectively, the combination therapies using TU2218 not only improved efficacy but also showed high safety profiles without weight loss or any toxicity signs, supporting the feasibility of the combination strategy of TU2218.
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD)
High-throughput screening identifies potential combinatorial therapies to overcome lenvatinib resistance in liver cancer (Section 27) - Mar 5, 2024 - Abstract #AACR2024AACR_6801;
Interestingly, EGFRi and lenvatinib were substantially synergistic in parental cells, suggesting that an upfront combination of these inhibitors could potentially be used before the emergence of lenvatinib resistance in liver cancer. We have established a lenvatinib-resistant liver cancer cell model and validated a drug screening assay to identify potential combinatorial therapies to overcome lenvatinib resistance in liver cancer.
- |||||||||| sorafenib / Generic mfg.
Targeting sorafenib-resistant HCCs by protein X-armed T cell immunotherapy (Section 30) - Mar 5, 2024 - Abstract #AACR2024AACR_6765;
To summarize, our study shows that Arm-T cells possess strong cytotoxic abilities against sorafenib-resistant HCC. These findings have implications for developing effective immuno-therapeutic strategies for patients with sorafenib-resistant HCCs.
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD)
Beyond the role of transcobalamin 1 (TCN1) as a vitamin B12-binding protein in hepatocellular carcinoma (Section 8) - Mar 5, 2024 - Abstract #AACR2024AACR_5969;
By analyzing the TCGA-LIHC dataset with confirmation by immunoprecipitation, we report, for the first time, that TCN1 directly interacts with integrin subunit alpha 3 (ITGA3), thereby regulating the Notch signaling pathway. Furthermore, ELISA results revealed the presence of the secretory form of TCN1 in HCC cells, which exerts a T-IC-enhancing effect on HCC cells via autocrine regulation.In conclusion, our study provides novel insights into how TCN1 functions in HCC via a non-canonical mechanism, which goes beyond its conventional role as a vitamin B12-binding protein and uncovers a potential novel therapeutic target for HCC.
- |||||||||| RGT-M001 / Rgenta Therap
RGT-M001, a first-in-class small molecule mRNA degrader of the oncogenic transcription factor c-Myb, demonstrated remarkable single agent anti-tumor efficacy in cancer patient-derived xenograft model (Section 27) - Mar 5, 2024 - Abstract #AACR2024AACR_5460;
As a single agent, RGT-M001 reduced in vivo C-MYB transcript levels by >80% at peak drug exposure and induced a remarkable tumor growth inhibition response (~70% TGI) in the ACCX11 PDx mouse model, surpassing the therapeutic benchmark Lenvatinib (40% TGI)...Finally, we showed that the combination of RGT-M001 with the Notch Inhibitor AL-101 resulted in complete inhibition of tumor growth.In conclusion, these data demonstrate that small molecules targeting RNA are a safe and effective approach to address previously undruggable protein targets. Down-regulation of C-MYB by our RNA-targeting small molecules is an attractive therapeutic strategy to treat ACC and other cancers driven by C-MYB dysregulations.
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD)
Identification of Annexin A1 as a novel driver of lenvatinib resistance in hepatocellular carcinoma (Section 26) - Mar 5, 2024 - Abstract #AACR2024AACR_5376;
Based on this observation, we further demonstrated the in vitro role of secretory ANXA1 in LenR HCC cells in inducing macrophage polarization towards the M2 phenotype. In conclusion, ANXA1 may regulate lenvatinib resistance intrinsically via the promotion of cancer stemness and extrinsically via the induction of an immunosuppressive TME.
- |||||||||| Combination therapy leads to decreased viability in cardiomyblasts cells (Section 27) - Mar 5, 2024 - Abstract #AACR2024AACR_4056;
We tested three TKIs (Axitinib, Cabozantinib, and Lenvatinib) and two ICIs (Nivolumab and Pembrolizumab), both solely and together, on rat ventricular myoblasts (H9c2) cells using clinically relevant concentrations by calculating the unbound serum drug concentrations found in cancer patients...We plan to further characterize whether these drug combinations lead to cardiomyocyte death and through which pathway. Additionally, our lab has successfully differentiated and validated human-induced pluripotent ventricular myocytes (hiPSC-CMs) and testing whether these monotherapies and combination therapies effect viability and functionality on human-induced pluripotent ventricular myocytes (hiPSC-CMs) is currently in progress.
- |||||||||| E7386 / Eisai, PRISM Pharma, Lenvima (lenvatinib) / Eisai, Merck (MSD)
E7386, a Wnt/?-catenin signaling modulator, suppresses the differentiation of regulatory T cells in combination with lenvatinib plus anti-PD-1 antibody (Section 27) - Mar 5, 2024 - Abstract #AACR2024AACR_4040;
Taken together, these results suggest a role for E7386 in suppressing the activation of Wnt/?-catenin signaling induced by LEN monotreatment in specific EC subtypes; this activity leads to enhanced antiangiogenic and antitumor activity with E7386 plus LEN combination therapy in a preclinical tumor model. In summary, these data suggest a suppressive role of E7386 on Treg differentiation, which leads to antitumor activity of E7386 in combination with lenvatinib and anti-PD-1 antibody in a preclinical tumor model.
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD)
Mass spectrometry profiling identifies ENO2 as a driver of lenvatinib resistance in hepatocellular carcinoma (Section 26) - Mar 5, 2024 - Abstract #AACR2024AACR_3983;
We further showed that ENO2 upregulation in HCC is positively correlated with stemness and hepatic progenitor marker signatures, as well as hypoxia, and subsequently demonstrated that ENO2 is regulated by hypoxia/HIF-1?, with hypoxia response element sequences located in the ENO2 promoter region. Research is underway to investigate the functional role and underlying molecular mechanisms associated with ENO2-driven lenvatinib resistance and cellular plasticity in HCC.
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