Safety and Preliminary Anti-Tumor Activity of TYRA-430 in Advanced Hepatocellular Carcinoma and Other Solid Tumors With Activating FGF/FGFR Pathway Aberrations

A vizsgálat adatai

Ki végzi

Tyra Biosciences, Inc

Azonosító

NCT06915753

A regiszteradat frissítve

2026. október 14.

Eredeti leírás

A Phase 1 study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamic (PD), and preliminary antitumor activity of TYRA-430 in cancers with FGF/FGFR pathway aberrations, including locally advanced/metastatic hepatocellular carcinoma and other advanced solid tumors.A teljes eredeti leírásKevesebb

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

A Phase 1 study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamic (PD), and preliminary antitumor activity of TYRA-430 in cancers with FGF/FGFR pathway aberrations, including locally advanced/metastatic hepatocellular carcinoma and other advanced solid tumors.

Bevonási feltételek: All Patients:; Age ≥ 18 years; Eastern Cooperative Oncology Group (ECOG) performance status of ≤1; Adequate end organ function; Ability to swallow oral formulations; Ability to understand and willingness to sign the ICF; Part A:; Histologically confirmed locally advanced unresectable/metastatic HCC or histologically confirmed advanced solid tumor with documented FGF/FGFR pathway alterations; For participants with histologically confirmed locally advanced or metastatic HCC:; Barcelona Clinic Liver Cancer (BCLC) stage B that is not eligible for locoregional therapy, or stage C; Child-Pugh Score class A; Must have previously received SOC appropriate for their tumor type. Any number of prior therapies, including FGFR inhibitors, are permitted; Agree to provide archival tumor tissue, if available. If an archived specimen is not available, a biopsy is not required; Part B, Cohort 1:; Histologically confirmed locally advanced/metastatic HCC who have previously received standard of care; Barcelona Clinic Liver Cancer (BCLC) stage B that is not eligible for locoregional therapy, or stage C; Child-Pugh Score class A; Availability of an archival formalin-fixed paraffin-embedded (FFPE) tumor tissue specimen for submission to sponsor-designated central laboratory for FGF19 IHC testing; At least 1 measurable lesion by RECIST v1.1; Part B, Cohort 2:; Histologically confirmed advanced solid tumor except FGFR3-altered urothelial carcinoma and primary central nervous system tumors who have previously received standard of care. Note: Participants with confirmed diagnosis of locally advanced or metastatic HCC are not eligible for Cohort 2; Must have an eligible activating gain-of-function alteration in the FGFR4 gene, or focal amplifications of FGF19; Archival tumor tissue biopsy specimen , if available. If a tissue biopsy specimen is not available, a biopsy is not required; At least 1 measurable lesion by RECIST v1.1.

Kizáró feltételek: Have not recovered from reversible toxicity of prior anticancer therapy to < Grade 1 or baseline (except toxicities that are not clinically significant or not expected to resolve, including but not limited to, alopecia, fatigue, skin discoloration, or Grade 1 neuropathy); Have received the following anticancer therapy:; Any immunotherapy or other antibody therapy within 28 days prior to the first dose of the study drug; A TKI < 5 days or 5X the terminal Phase elimination half-lives, whichever is longer, prior to the first dose of TYRA-430; Other systemic therapy not listed above < 14 days prior to the first dose of the study drug; Participant discontinued a prior anti-FGFR therapy due to significant toxicity; Prior treatment with pan-FGFR inhibitors or FGFR4-selective inhibitors; Part B, Cohort 2:; Have disease that is suitable for local therapy administered with curative intent; History of or current uncontrolled cardiovascular disease; Have a diagnosis of primary CNS malignancies; Gastrointestinal disorders that will affect oral administration or absorption of TYRA-430; Histologically confirmed urothelial cancer; Has a serum phosphorus level > upper limit of normal (ULN) during screening that remains >ULN despite medical management; All Patients:; Active, symptomatic, or untreated brain metastases; Females who are pregnant, breastfeeding, or planning to become pregnant and males who plan to father a child while enrolled in this study; Any reason that, in the view of investigator, would substantially impair the ability of the participant to comply with study procedures and increase the risk to the participant; Part B, Cohort 1:; Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC; Histologically confirmed locally advanced/metastatic HCC.

ClinicalTrials.gov NCT06915753