- |||||||||| Loqtorzi (toripalimab-tpzi) / Shanghai Junshi Biosci, Coherus Biosci, Lenvima (lenvatinib) / Eisai, Merck (MSD)
Trial completion date, Trial primary completion date, Metastases: Lenvatinib Combined Toripalimab in Advanced Hepatocellular Carcinoma (clinicaltrials.gov) - Mar 29, 2023 P2, N=76, Recruiting, Trial completion date: Apr 2023 --> Nov 2023 Trial completion date: Apr 2023 --> Apr 2025 | Trial primary completion date: Apr 2022 --> Apr 2024
- |||||||||| Loqtorzi (toripalimab-tpzi) / Shanghai Junshi Biosci, Coherus Biosci, Lenvima (lenvatinib) / Eisai, Merck (MSD)
Biomarker, Trial completion date, Trial primary completion date, Metastases: Toripalimab Plus Lenvatinib as Second-line Treatment in Advanced Biliary Tract Cancers (clinicaltrials.gov) - Mar 29, 2023 P2, N=44, Recruiting, Trial completion date: Apr 2023 --> Apr 2025 | Trial primary completion date: Apr 2022 --> Apr 2024 Trial completion date: Dec 2022 --> Dec 2024 | Trial primary completion date: Jul 2022 --> Jul 2024
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), Lenvima (lenvatinib) / Eisai, Merck (MSD)
Trial completion, Enrollment change, Metastases: Lenvatinib Combined Pembrolizumab in Advanced Hepatobiliary Tumors (clinicaltrials.gov) - Mar 29, 2023 P2, N=32, Completed, Trial completion date: Mar 2023 --> Sep 2024 | Trial primary completion date: Sep 2022 --> Sep 2023 Recruiting --> Completed | N=50 --> 32
- |||||||||| Review, Journal: Endocrine-Related Adverse Conditions Induced by Tyrosine Kinase Inhibitors. (Pubmed Central) - Mar 26, 2023
Metabolic alterations during TKI treatment range from hypoglycemia with imatinib and dasatinib to hyperglycemia with nilotinib; dyslipidemia improved with imatinib and worsened with nilotinib, sunitinib, pazopanib, sorafenib, and famitinib...Hormone deficiencies are easily managed by replacement therapy, while endocrine hyperfunction may be improved by symptomatic treatment. Severe situations should be managed in coordination with the oncologist, trying to limit the need for TKI dose reduction or interruption.
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD)
Journal, PD(L)-1 Biomarker, IO biomarker: Correlation and efficacy of TACE combined with lenvatinib plus PD-1 inhibitor in the treatment of hepatocellular carcinoma with portal vein tumor thrombus based on immunological features. (Pubmed Central) - Mar 25, 2023 Compared with TACE+LEN, the triple combination treatment of TACE+LEN?+?PD-1 has more promising clinical outcomes and acceptable safety in patients with HCC and PVTT. Child-Pugh grade, PVTT classification, and IL-6, IL-17, IFN-?, and VEGF levels are independent prognostic factors for survival time.
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), Lenvima (lenvatinib) / Eisai, Merck (MSD)
Review, Journal, Checkpoint inhibition, MSi-H Biomarker, PD(L)-1 Biomarker, IO biomarker, Metastases: A rapidly evolving landscape: immune checkpoint inhibitors in pretreated metastatic endometrial cancer. (Pubmed Central) - Mar 25, 2023 Only the phase III KEYNOTE-775 trial reported a statistically significant overall survival improvement for the combination of pembrolizumab plus lenvatinib compared with docetaxel or paclitaxel regardless of MMR/MSI status. Pembrolizumab plus lenvatinib is indicated for patients with unselected pretreated metastatic endometrial cancer and pembrolizumab monotherapy is a preferred option for patients with MMRd/MSI-H tumors.
- |||||||||| Tuoyi (toripalimab) / Shanghai Junshi Biosci, Coherus Biosci, Lenvima (lenvatinib) / Eisai, Merck (MSD)
P2 data, Clinical Trial,Phase III, Journal, PD(L)-1 Biomarker, IO biomarker, Metastases: Toripalimab combined with lenvatinib and GEMOX is a promising regimen as first-line treatment for advanced intrahepatic cholangiocarcinoma: a single-center, single-arm, phase 2 study. (Pubmed Central) - Mar 24, 2023 P2 A phase-III, multicenter, double-blinded, randomized study to validate our findings was approved by the National Medical Products Administration (NMPA, No. 2021LP01825).Trial registration Clinical trials: NCT03951597.
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD)
Journal: METTL3-mA-EGFR-axis drives lenvatinib resistance in hepatocellular carcinoma. (Pubmed Central) - Mar 24, 2023 EGFR overexpression abrogated the METTL3 knocked down-induced cell growth arrest upon lenvatinib treatment in HCC-LR cells. Thus, we concluded that targeting METTL3 using specific inhibitor STM2457 improved the sensitivity to lenvatinib in vitro and in vivo, indicating that METTL3 may be a potential therapeutic target to overcome lenvatinib resistance in HCC.
- |||||||||| Tyvyt (sintilimab) / Eli Lilly, Lenvima (lenvatinib) / Eisai, Merck (MSD)
Enrollment open, Checkpoint inhibition, Metastases: Cryoablation Combined With Sintilimab Plus Lenvatinib in Patients With Immune Checkpoint Inhibitor Previously Treated Advanced Biliary Tract Cancer ?CASTLE-08? (clinicaltrials.gov) - Mar 24, 2023 P2, N=25, Recruiting, Thus, we concluded that targeting METTL3 using specific inhibitor STM2457 improved the sensitivity to lenvatinib in vitro and in vivo, indicating that METTL3 may be a potential therapeutic target to overcome lenvatinib resistance in HCC. Not yet recruiting --> Recruiting
- |||||||||| Review, Journal, PD(L)-1 Biomarker, IO biomarker: Anti-angiogenic agents for NSCLC following first-line immunotherapy: Rationale, recent updates, and future perspectives. (Pubmed Central) - Mar 21, 2023
Areas of focus in the future will include further molecular dissection of the mechanisms of resistance to immunotherapy and the various response-progression profiles to immunotherapy observed in the clinic and the monitoring of the dynamics of immunomodulation over the course of treatment. Improved understanding of these phenomena may help identify clinical biomarkers and inform the optimal use of anti-angiogenics in the treatment of individual patients.
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD)
Retrospective data, Journal: Association between thyroid cancer and cardiovascular disease: A meta-analysis. (Pubmed Central) - Mar 21, 2023 Secondary outcomes included cardiovascular disease events among those with thyroid cancer that received or did not receive radioactive iodine or lenvatinib...Thyroid cancer was significantly associated with a higher risk for cerebrovascular disease and atrial fibrillation; however, the hazard risk was not different between patients with and without radioactive iodine treatment. Thyroid cancer treatment should be individualized considering the potential harms and benefits to cardiovascular health.
- |||||||||| Opdivo (nivolumab) / Ono Pharma, BMS, Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen
Retrospective data, Journal, Checkpoint inhibition, Metastases: Immune checkpoint inhibitors combined with tyrosine kinase inhibitors or immunotherapy for treatment-na (Pubmed Central) - Mar 21, 2023 Thyroid cancer treatment should be individualized considering the potential harms and benefits to cardiovascular health. Randomized controlled trials (RCTs) on therapies recommended by the latest EAU and ESMO guidelines for treatment-na
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD)
Trial completion date, Combination therapy: Trial to Assess Safety and Efficacy of Lenvatinib (18 mg vs. 14 mg) in Combination With Everolimus in Participants With Renal Cell Carcinoma (clinicaltrials.gov) - Mar 15, 2023 P2, N=343, Active, not recruiting, Compared with TACE plus sorafenib, TACE plus lenvatinib can better control disease progression, reduce the levels of tumor markers, and stabilize the liver function of patients with intermediate-advanced hepatocellular carcinoma. Trial completion date: Apr 2023 --> Aug 2023
- |||||||||| Journal, HEOR, Cost-effectiveness, Cost effectiveness, Metastases: Cost-Effectiveness Analysis of Six Immunotherapy-Based Regimens and Sunitinib in Metastatic Renal Cell Carcinoma: A Public Payer Perspective. (Pubmed Central) - Mar 14, 2023
The seven treatment drug strategies included atezolizumab + bevacizumab, avelumab + axitinib, pembrolizumab + axitinib, nivolumab + ipilimumab (NI), nivolumab + cabozantinib, lenvatinib + pembrolizumab, and sunitinib...In sensitivity analyses, this ICER fell below $150,000 USD/QALY if the initial 4-month cost of NI decreased by 22%-38%. NI was the most effective combination for mRCC, but at a willingness-to-pay threshold of $150,000 USD/QALY, sunitinib was the most cost-effective approach.
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD)
Sorafenib and Lenvatinib induce vascular responses in patient derived HCC on-Chip models (Section 4; Poster Board #18) - Mar 14, 2023 - Abstract #AACR2023AACR_8840; These co-cultures are highly suitable for studying specific cell types as well as patient-specific responses. We envision that this patient derived model will evolve to become a platform for understanding the interplay between angiogenesis, stroma and immune infiltrate in HCC.
- |||||||||| Dissecting the role of CDK4 in liposarcoma (Section 9; Poster Board #22) - Mar 14, 2023 - Abstract #AACR2023AACR_8587;
In particular, we pointed out encouraging results of sequential treatment combining CDK4 inhibitor palbociclib and chemotherapy. Furthermore, preliminary analyses highlighted the involvement of this biomarker as a potential prognostic tool for STS.
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD)
Chronic VEGF-C signaling exacerbates the progression of non-alcoholic steatohepatitis and hepatocarcinoma through endothelial VEGFR2 and VEGFR3 (Section 3; Poster Board #23) - Mar 14, 2023 - Abstract #AACR2023AACR_7690; Analysis of vehicle treated and lenvatinib treated livers by single nuclei RNA sequencing uncovered significant changes in endothelial cell genes associated with extracellular interactions and inflammation, as well as hepatocyte genes involved in lipid synthesis and metabolism. Taken together, these findings indicate that chronic VEGF-C production in NASH plays a role in promoting liver fibrosis and steatosis as well as HCC development, and that blockade of the downstream receptors for VEGF-C, VEGFR2 and VEGFR3, may be a promising therapeutic strategy to mitigate disease severity.
- |||||||||| Nailike (olverembatinib) / Ascentage Pharma
Olverembatinib (HQP1351) enhances antitumor effects of immunotherapy in renal cell carcinoma (RCC) (Section 21; Poster Board #5) - Mar 14, 2023 - Abstract #AACR2023AACR_7411; In recent years, TKIs, including axitinib, lenvatinib, and cabozantinib, plus immunotherapy have been approved to treat advanced RCC...Taken together, these data suggest that combining olverembatinib with a CPI confers synergistic antitumor effects in an RCC cancer mouse model by targeting tumor growth, angiogenesis, and immune regulation. This novel combination may provide an alternative approach to enhance treatment effects with CPIs in renal cancers.
- |||||||||| HC-5404 / HiberCell
Inhibition of PERK by HC-5404 sensitizes clear cell renal cell carcinoma tumor models to anti-angiogenic tyrosine kinase inhibitors (Section 20; Poster Board #7) - Mar 14, 2023 - Abstract #AACR2023AACR_6200; P1a Furthermore, the approvals for VEGFR-targeting receptor tyrosine kinase inhibitors (VEGFR-TKIs), cabozantinib in second-line, and tivozanib in third-line RCC patients were based on modest objective response rates and median progression-free survival...We demonstrate that axitinib, cabozantinib, lenvatinib, and sunitinib all activate PERK in 786-O ccRCC xenografts in a dose-responsive manner...The combination treatment significantly improved TGI relative to either monotherapy, resulting in tumor regression of ~20%. Taken together, these findings highlight that by disrupting an adaptive stress response evoked by VEGFR-TKIs, HC-5404 presents a clinical opportunity to enhance the anti-tumor effects of well-established standard of care therapies in ccRCC.
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