NCT06915753招募中1 期
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
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 32
- 主要终点
- Maximum tolerated dose (MTD)
研究概览
简要总结
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.
详细描述
This is an open-label, multi-center, first-in-human, Phase 1 global study of TYRA-430, a first-in-class, selective, reversible fibroblast growth factor receptor (FGFR) 4 and 3 inhibitor, in locally advanced/metastatic hepatocellular carcinoma and other advanced solid tumors that contain FGF/FGFR pathway aberrations.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All Patients:
- •Age ≥ 18 years
- •Eastern Cooperative Oncology Group (ECOG) performance status of ≤
- •Adequate end organ function.
- •Ability to swallow oral formulations.
- •Ability to understand and willingness to sign the ICF.
- •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 no older than 2 years from the time of enrollment, 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 obtained ≤2 years prior to screening for submission to sponsor-designated central laboratory for FGF19 IHC testing.
- •At least 1 measurable lesion by RECIST v1.
- •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
- •Must have an eligible activating gain-of-function alteration in the FGFR3 or FGFR4 gene, or focal amplifications of FGF19
- •Archival tumor tissue biopsy specimen no older than 2 years from the time of enrollment, if available. If a tissue biopsy specimen is not available, a biopsy is not required.
- •At least 1 measurable lesion by RECIST v1.
排除标准
- •All Patients:
- •Have disease that is suitable for local therapy administered with curative intent.
- •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-
- •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, defined as hepatotoxicity ≥ Grade 3 or any Grade 4 toxicity according to CTCAE v5.
- •Has a serum phosphorus level > upper limit of normal (ULN) during screening that remains >ULN despite medical management.
- •History of or current uncontrolled cardiovascular disease.
- •Active, symptomatic, or untreated brain metastases.
- •Have a diagnosis of primary CNS malignancies.
- •Gastrointestinal disorders that will affect oral administration or absorption of TYRA-
- •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.
- •Prior treatment with pan-FGFR inhibitors or FGFR4-selective inhibitors.
- •Part B, Cohort 2:
- •Histologically confirmed locally advanced/metastatic HCC.
- •Histologically confirmed urothelial cancer.
研究组 & 干预措施
Part B - Cohort 2 Dose Expansion
Experimental
Dose expansion group for TYRA-430 monotherapy in advanced solid tumors at a dose(s) determined in Part A.
干预措施: TYRA-430 (Drug)
Part A - Dose Escalation
Experimental
Dose escalation of TYRA-430 as monotherapy at various dose levels.
干预措施: TYRA-430 (Drug)
Part B - Cohort 1 Dose Expansion
Experimental
Dose expansion group for TYRA-430 monotherapy in advanced HCC at a dose(s) determined in Part A.
干预措施: TYRA-430 (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD)
时间窗: Up to 1 year
MTD determination: dose limiting toxicity (DLT) rate in the first 28-day cycle
Rate and severity of adverse events of TYRA-430 as monotherapy
时间窗: First dose of study drug through 28 days after the last dose of study drug
Number of participants with TEAEs as assessed by CTCAE, v5.0
Recommended Phase 2 dose(s) of TYRA-430
时间窗: Up to 2 years
To determine recommended Phase 2 dose(s) of TYRA-430
次要结局
- Cmax(Up to 2 years)
- Tmax(Up to 2 years)
- AUC0-last(Up to 2 years)
- AUCTau(Up to 2 years)
- AUC0-∞(Up to 2 years)
- Vd/F(Up to 2 years)
- t1/2(Up to 2 years)
- CL/F(Up to 2 years)
- Overall Response Rate (ORR)(Up to 3.5 years)
- Duration of Response (DOR)(Up to 3.5 years)
- Disease Control Rate (DCR)(Up to 3.5 years)
- Time to Response (TTR)(Up to 3.5 years)
研究者
研究点 (32)
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