telatinib (BAY 57- 9352) / EddingPharm - LARVOL DELTA

Activation of stimulator of interferon genes (STING) and inhibition of vascular endothelial growth factor receptor (VEGFR) by telatinib induce antitumor activity. (PubMed, J Biol Chem) - "Moreover, we showed that telatinib-mediated STING activation contributed to the antitumor effects in tumor-bearing mouse models. In summary, our results reveal that telatinib, a previously identified VEGFR2 inhibitor, activates STING signaling, highlighting its potential in cancer immunotherapy."

Journal • Oncology • STING

Safety and Efficacy of Telatinib in Combination With Keytruda in Subjects With Advanced Stomach and Gastroesophageal Junction Cancers or Hepatocellular Carcinoma (clinicaltrials.gov) - P2 | N=16 | Completed | Sponsor: Andrew Hendifar, MD | Active, not recruiting ➔ Completed | Trial completion date: Feb 2026 ➔ Oct 2025

Trial completion • Trial completion date • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • PD-L1

Safety and Efficacy of Telatinib in Combination With Keytruda in Subjects With Advanced Stomach and Gastroesophageal Junction Cancers or Hepatocellular Carcinoma (clinicaltrials.gov) - P2 | N=16 | Active, not recruiting | Sponsor: Andrew Hendifar, MD | Trial completion date: Feb 2025 ➔ Feb 2026

Trial completion date • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor • PD-L1

Multiomic traits reveal that critical irinotecan-related core regulator FSTL3 promotes CRC progression and affects ferroptosis. (PubMed, Cancer Cell Int) - "We confirmed that irinotecan-related regulators, especially FSTL3, have effective prognostic value in CRC and speculated that FSTL3 may promote CRC progression and affect ferroptosis, which is beneficial for identifying candidate targeted irinotecan-related regulators and accurate individualized treatment strategies for CRC."

Journal • Colorectal Cancer • Oncology • Solid Tumor • E2F1 • GPX4 • HSPB1 • MSI • RGS4 • SLC7A11 • STAT1 • TMEM98

Ubiquitination-related Gene UBTD1 Mediates Poor Prognosis of Colorectal Cancer and Affects Colorectal Cancer Cell Proliferation and Ferroptosis. (PubMed, Recent Pat Anticancer Drug Discov) - "Our study demonstrated that UBTD1 is a prognostic marker for CRC in the regulation of ubiquitination and the tumor immune microenvironment and may serve as a modulator of ferroptosis."

Journal • Colorectal Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • UBB

Discovery of Small Molecule Inhibitors Targeting CTNNB1 (β-catenin) for Endometrial cancer: Employing 3D QSAR, Drug-Likeness Assessment, ADMET Predictions, Molecular Docking and Simulation. (PubMed, Curr Med Chem) - "Through a comprehensive screening process employing in silico drug design methods, this study successfully identified five potential human anticancer drug candidates targeting the beta-catenin protein. These findings offer a foundation for further experimental validation and development towards the treatment of EC."

Journal • Endometrial Cancer • Oncology • Solid Tumor • CTNNB1

Analysis of the role of CHPF in colorectal cancer tumorigenesis and immunotherapy based on bioinformatics and experiments. (PubMed, Discov Oncol) - "CHPF could promote the proliferation and migration of CRC cells and lead to poor prognosis, possibly through wnt pathways as well as changes in TME. Patients with high expression of CHPF had poor efficacy in immunotherapy, which might be related to Tregs cell infiltration. Above all, it might offer more reliable guidance for future immunotherapy."

IO biomarker • Journal • Tumor mutational burden • Colorectal Cancer • Gastrointestinal Cancer • Microsatellite Instability • Oncology • Solid Tumor • CHPF • MSI • PD-1 • TMB

Safety and Efficacy of Telatinib in Combination With Keytruda in Subjects With Advanced Stomach and Gastroesophageal Junction Cancers or Hepatocellular Carcinoma (clinicaltrials.gov) - P2 | N=17 | Active, not recruiting | Sponsor: Andrew Hendifar, MD | Trial completion date: Feb 2024 ➔ Feb 2025

Combination therapy • Metastases • Trial completion date • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor • PD-L1

Safety and Efficacy of Telatinib in Combination With Keytruda in Subjects With Advanced Stomach and Gastroesophageal Junction Cancers or Hepatocellular Carcinoma (clinicaltrials.gov) - P2 | N=17 | Active, not recruiting | Sponsor: Andrew Hendifar, MD | Recruiting ➔ Active, not recruiting | N=45 ➔ 17

Combination therapy • Enrollment change • Enrollment closed • Metastases • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor • PD-L1

Identification of stable housekeeping genes for induced pluripotent stem cells and -derived endothelial cells for drug testing. (PubMed, Sci Rep) - "Based on the comprehensive ranking of Reffinder, the stability of the top two genes-RPL36AL and TMBIM6, and the bottom two genes-UBA1 and B2M, were further studied in iPSC-EC with and without genetic manipulation, and after treatment with telatinib. Using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR), it was shown that gene expression of the top two housekeeping genes, RPL36AL and TMBIM6, remained stable during drug treatment. We identified a panel of housekeeping genes that could be utilized in various conditions using iPSC and iPSC-derived endothelial cells as well as genetically modified iPSC for drug treatment."

Journal • B2M • GAPDH • HPRT1 • KEAP1 • TMBIM6

Safety and Efficacy of Telatinib in Combination With Keytruda in Subjects With Advanced Stomach and Gastroesophageal Junction Cancers or Hepatocellular Carcinoma (clinicaltrials.gov) - P2 | N=45 | Recruiting | Sponsor: Andrew Hendifar, MD | Active, not recruiting ➔ Recruiting

Combination therapy • Enrollment open • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor • PD-L1

Safety and Efficacy of Telatinib in Combination With Keytruda in Subjects With Advanced Stomach and Gastroesophageal Junction Cancers or Hepatocellular Carcinoma (clinicaltrials.gov) - P2 | N=45 | Active, not recruiting | Sponsor: Andrew Hendifar, MD | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor • PD-L1

A Phase I multiple-dose escalation study to assess the safety, tolerability, and pharmacokinetics of VEGF-receptor inhibitor telatinib (EOC315) in Chinese patients with advanced solid tumors. (ASCO 2019) - P1; "This study demonstrated the safety and tolerability of Telatinib (EOC315) in a multiple dose escalation design at 600, 900, and 1200 mg PO bid in Chinese patients with advanced refractory solid tumor. Telatinib AUC increased dose-proportionally from 600 mg to 900 mg bid, where 900 mg Telatinib bid is the maximum feasible and recommended dose for future studies in Chinese patients with advanced tumors. Clinical trial information: NCT03175497"

Clinical • P1 data • PK/PD data

Safety and Efficacy of Telatinib in Combination With Keytruda in Subjects With Advanced Stomach and Gastroesophageal Junction Cancers or Hepatocellular Carcinoma (clinicaltrials.gov) - P2; N=45; Recruiting; Sponsor: Andrew Hendifar, MD; Not yet recruiting ➔ Recruiting

Enrollment open • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor • PD-L1

Safety and Efficacy of Telatinib in Combination With Keytruda in Subjects With Advanced Stomach and Gastroesophageal Junction Cancers or Hepatocellular Carcinoma (clinicaltrials.gov) - P2; N=45; Not yet recruiting; Sponsor: Andrew Hendifar, MD

Clinical • Combination therapy • New P2 trial • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor • PD-L1

A study of telatinib in combination with chemotherapy in subjects with advanced gastric cancer (clinicaltrials.gov) - P2, N=48; N=35 -> 48; Active, not recruiting -> Completed; Completion date: May 2011 -> Jan 2012

Completion date • Enrollment • Trial completion • Oncology

Phase I Evaluation of Telatinib, a Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor, in Combination with Irinotecan and Capecitabine in Patients with Advanced Solid Tumors (Clin Cancer Res) -

Continuous administration of 900 mg telatinib twice daily can be safely combined with irinotecan (180 mg/m(2)) and capecitabine (1,000 mg/m(2) twice daily, day 1-14) and is the recommended schedule for further phase II studies. Tumor shrinkage and disease stabilization was observed

ACT Biotech receives orphan drug designation for Telatinib, an orally available and highly selective kinase inhibitor, in Gastric Cancer (Businesswire) -

[ACT Biotech anticipates initiation of P3 trial of telatinib for 1st line gastric cancer by the end of 2010, with NDA filing targeted for 2013; Anticipates launch of drug in 2014; Similar process for filing for orphan designation is initiated in Europe; Orphan drug designation; Anticipated P3 trial initiation; Anticipated NDA filing]

Anticipated P3 trial initiated • Orphan drug

Telatinib is an effective targeted therapy for pseudomyogenic hemangioendothelioma. (PubMed, Clin Cancer Res) - "We provide a biological substantiation of a complete clinical remission that was seen in a patient with PHE, showing that telatinib indirectly interferes with the self-regulated expression of the fusion product. Thus, telatinib or any other currently available VEGFR1-4/PDGFRA inhibitor, could be a highly specific treatment option for patients with multifocal unresectable PHE."

Journal

Phase I study of telatinib (BAY 57-9352): analysis of safety, pharmacokinetics, tumor efficacy, and biomarkers in patients with colorectal cancer (Vasc Cell) - P1; N=39; No clear relationship between telatinib dose & individual Cmax & AUC in the 600 mg bid to 1500 mg bid dose range; No partial remission according to RECIST reached, but 41% of the pts reached some tumour shrinkage

P1 data

Telatinib Safety and Pharmacokinetics Study in China Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=15; Completed; Sponsor: EddingPharm Oncology Co., LTD.; Recruiting ➔ Completed; N=24 ➔ 15; Trial primary completion date: Mar 2018 ➔ Aug 2018

Clinical • Enrollment change • Trial completion • Trial primary completion date

Telatinib in Combination With Capecitabine/ Oxaliplatin in 1st Line Gastric or GEJ Cancer (clinicaltrials.gov) - P2; N=90; Recruiting; Sponsor: EddingPharm Oncology Co., LTD.; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open

Telatinib in Combination With Capecitabine/ Oxaliplatin in 1st Line Gastric or GEJ Cancer (clinicaltrials.gov) - P2; N=90; Not yet recruiting; Sponsor: EddingPharm Oncology Co., LTD.

Clinical • Combination therapy • New P2 trial