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

Ki vehet részt

• 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

Ki nem vehet részt

• 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