Undisclosed FGFR4 inhibitor / Tyra Biosci - LARVOL DELTA

A multicenter, open-label, first-in-human study of TYRA-430 in advanced hepatocellular carcinoma and other solid tumors with activating FGF/FGFR pathway aberrations (SURF431) (ESMO 2025) - P1 | "FGF19 signals through FGF receptor 4 (FGFR4), however, selective investigational FGFR4 inhibitors, such as fisogatinib and roblitinib have shown limited clinical efficacy. Part B Cohort 1 dose expansion will enroll approximately 40 patients with advanced HCC at RP2D(s), focusing on FGF19-positive patients; approximately 20 patients with FGFR3/4 altered solid tumors will be enrolled in Part B Cohort 2. The study is planned for approximately 25 centers in North America, Asia, and Europe."

Clinical • First-in-human • Metastases • P1 data • Brain Cancer • Hepatocellular Cancer • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • FGF19 • FGFR3 • FGFR4

TYRA-430: First reversible FGFR4/3 inhibitor designed to overcome current challenges in FGF19-driven hepatocellular carcinoma treatment. (ASCO-GI 2025) - "In vitro data showed that TYRA-430 displayed superior potency over the reversible multi-kinase inhibitors sorafenib and lenvatinib, and the covalent FGFR4 inhibitors fisogatinib (BLU-554) and roblitinib (FGF401) in KLB/FGF-19/FGFR3/4 driven models of HCC (Hep3B, HuH-7, and JHH-7 cells). TYRA-430 was active and potent in multiple KLB/FGF-19/FGFR3/4 models of human hepatocellular carcinoma in vitro and in vivo. Moreover, TYRA-430 displayed potent activity against known FGFR4 resistance mutations compared to covalent FGFR4-specific inhibitors in the clinic. TYRA-430 will be investigated in a Phase 1 clinical trial in hepatocellular carcinoma and other advanced solid tumors."

Gastric Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • FGF19 • FGFR3 • FGFR4

Roundtable Discussion: Abou-Alfa Evaluates Choice of Therapy for HCC Based on Patient Factors (Targeted Oncology) - "During a Targeted Oncology case-based roundtable event, Ghassan K. Abou-Alfa, MD, MBA, discussed the case of a patient with hepatocellular carcinoma whose comorbidities impacted the choice of treatment....ABOU-ALFA: That is a great point that you bring up. [There are] a few points [to consider] about the biopsy. [Concerning] LI-RADS...I spoke with the radiologist who wrote the final LI-RADS radiologic assessments....ABOU-ALFA: [The patient] had Crohn disease, and she [also] bled from varices and she had banding 2 months ago. My question is, with varices, what's your comfort zone? [At what point do] you think you can give bevacizumab [Avastin]? [Do you not wait] at all, wait 2 months, 4 months, 6 months, or 1 year?"

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