A Phase 1 Multicenter, Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of SHY-ONC6 in Participants With Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 4
- 主要终点
- Incidence of Dose-Limiting Toxicities (DLTs), Adverse Events (AEs), and Serious Adverse Events (SAEs)
研究概览
简要总结
This is a Phase 1, first-in-human (FIH), open-label, multicenter study designed to evaluate the safety, tolerability, PK, and preliminary anti-tumor activity of SHY-ONC6 in participants with advanced or metastatic solid tumors who have progressed on or are intolerant to standard therapies. The study will consist of 2 parts: a dose escalation part (Phase 1a) and a dose expansion part (Phase 1b).
详细描述
This is a Phase 1, first-in-human (FIH), open-label, multicenter study designed to evaluate the safety, tolerability, PK, and preliminary anti-tumor activity of SHY-ONC6 in participants with advanced or metastatic solid tumors who have progressed on or are intolerant to standard therapies. The study will consist of 2 parts: a dose escalation part (Phase 1a) and a dose expansion part (Phase 1b).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Male or female ≥18 years of age.
- •Life expectancy >3 months.
- •ECOG performance status 0-
- •Histologically/cytologically confirmed advanced or metastatic solid tumors that have progressed on or are intolerant/unsuitable for standard therapies. Eligible tumor types: TNBC, HR+ breast cancer, colon cancer, gastric cancer, HCC, NSCLC (adeno and squamous), mesothelioma, pancreatic cancer, HRPC, soft tissue sarcoma; other tumor types after Medical Monitor discussion. Stable CNS metastases ≥4 weeks post-radiotherapy and off steroids ≥14 days are permitted.
- •≥1 measurable lesion per RECIST v1.1 (prostate cancer with bone-only disease and elevated PSA assessed by PCWG3).
- •Accessible tumor for biopsy
- •Adequate organ/bone marrow function.
- •Willingness and ability to provide informed consent.
- •Negative serum pregnancy test and use of effective contraception through 90 days after last dose for women of childbearing potential.
- •Male participants must use barrier contraception or abstinence and not donate sperm through 90 days after last dose.
排除标准
- •High-risk cardiovascular disease.
- •Concurrent anti-cancer treatment.
- •Active infection requiring systemic treatment within 2 weeks pre-dose.
- •History of another malignancy (with standard exceptions for in situ disease, non-melanoma skin cancers, and remission ≥2 years).
- •Active HBV (HBV-DNA >ULN), HCV (HCV-RNA >ULN), or HIV (well-controlled HIV with CD4 ≥350 cells/µL and undetectable viral load permitted); AIDS-defining opportunistic infection within 12 months.
- •Compromised pulmonary function within 6 months pre-dose .
- •Pregnancy or breastfeeding.
- •Recent radiotherapy, systemic anti-tumor therapy, other investigational therapy without appropriate washout.
- •Major surgery ≤4 weeks pre-dose.
- •Unable to swallow tablets or conditions affecting GI absorption.
- •Any medical or psychiatric disorders affecting compliance and/or interpretation of study results.
- •Persistent toxicities from prior anti-cancer therapy (exceptions apply)
- •Clinically significant corneal disease.
- •Unable to comply with prohibited concomitant medication restrictions.
研究组 & 干预措施
SHY-ONC6
Participants receive SHY-ONC6 administered orally once daily. Phase 1a, sequential dose levels are evaluated under accelerated titration and BOIN dose-escalation design. In Phase 1b, participants will be evaluated in disease-specific expansion cohorts and receive SHY-ONC6 at the RP2D range identified in Phase 1a.
干预措施: SHY-ONC6 (Drug)
结局指标
主要结局
Incidence of Dose-Limiting Toxicities (DLTs), Adverse Events (AEs), and Serious Adverse Events (SAEs)
时间窗: Dose-limiting toxicities assessed from first dose through Day 21 of Cycle 1 (each cycle is 21 days). Adverse events and serious adverse events collected from first dose through 30 days after last dose.
Adverse events and serious adverse events graded per NCI CTCAE v6.0; supported by laboratory tests, vital signs, physical examinations, and triplicate 12-lead ECG. Dose-limiting toxicities assessed during Cycle 1 (Days 1 through 21).
Maximum Tolerated Dose (MTD)
时间窗: Determined at the end of the Cycle 1 dose-limiting toxicity evaluation period (Cycle 1 is 21 days).
MTD determined using the BOIN (Bayesian Optimal Interval) design, with a target dose-limiting toxicity rate of 0.30, based on dose-limiting toxicity incidence observed during Cycle 1.
Recommended Phase 2 Dose (RP2D)
时间窗: Phase 1a: at the end of Cycle 1 (each cycle is 21 days). Phase 1b: through end of treatment plus a 30-day safety follow-up period.
Phase 1a: RP2D range determined from dose-limiting toxicity, adverse event, and serious adverse event incidence together with the MTD determination. Phase 1b: RP2D defined by integrated safety, efficacy, pharmacodynamic, and pharmacokinetic data.
次要结局
- Terminal Elimination Half-Life (t1/2)(Cycle 1 Day 1; Day 2 (24 hours post-dose); Day 8; and pre-dose on Day 15. Pre-dose and post-dose on Day 1 of subsequent cycles (each cycle is 21 days).)
- Maximum Plasma Concentration (Cmax)(Cycle 1 Day 1; Day 2 (24 hours post-dose); Day 8; and pre-dose on Day 15. Pre-dose and post-dose on Day 1 of subsequent cycles (each cycle is 21 days).)
- Area Under the Plasma Concentration-Time Curve (AUC)(Cycle 1 Day 1; Day 2 (24 hours post-dose); Day 8; and pre-dose on Day 15. Pre-dose and post-dose on Day 1 of subsequent cycles (each cycle is 21 days).)
- Time to Maximum Plasma Concentration (Tmax)(Cycle 1 Day 1; Day 2 (24 hours post-dose); Day 8; and pre-dose on Day 15. Pre-dose and post-dose on Day 1 of subsequent cycles (each cycle is 21 days).)
- Trough Plasma Concentration (Ctrough)(Pre-dose on Day 15 of Cycle 1 and pre-dose on Day 1 of subsequent cycles (each cycle is 21 days).)
- Overall Survival (OS)(From first dose until death, withdrawal, loss to follow-up, or study termination, assessed up to an estimated 12 months after last dose of study drug.)
- Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1b)(From first dose through end of treatment plus a 30-day safety follow-up period.)
- Anti-Tumor Activity - Objective Response Rate(Baseline through study completion, an average of 18 months.)
- Anti-Tumor Activity - Best Overall Response (BOR)(Baseline through study completion, an average of 18 months.)
- Anti-Tumor Activity - Time to Response (TTR)(From baseline until first documented response, assessed up to an estimated 18 months.)
- Anti-Tumor Activity - Duration of Response (DOR)(Baseline through study completion, an average of 18 months.)
- Anti-Tumor Activity - Progression-Free Survival(Baseline through study completion, an average of 18 months.)