An Open-Label, Phase 1 Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of ACC-1898 (Tyrosine Kinase Inhibitor) in Adult Participants With Advanced Solid Tumors.
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 40
- 主要终点
- Incidence of Dose-Limiting Toxicities (DLTs) Part 1 (Dose Escalation)
研究概览
简要总结
This is a research study of an experimental drug called ACC-1898. ACC-1898 is an oral tyrosine kinase inhibitor (TKI) that blocks several proteins kinases which may help cancer cells grow and spread.
The purpose of this Phase 1 clinical trial is to find a safe dose of ACC-1898 and to understand how the body absorbs, distributes, and eliminates the drug (pharmacokinetics / PK). The study will also look for early signs that ACC-1898 may slow or shrink tumors and explore possible biological markers related to drug activity.
Adults with advanced or metastatic solid tumors who have no remaining standard treatment options may take part.
All participants will receive ACC-1898 tablets by mouth once daily in repeating 21-day cycles. Treatment may continue for up to two years if the cancer does not worsen and side effects are manageable.
Safety information, laboratory results and imaging scans (CT or MRI) will be collected regularly.
The study will first test different dose levels (dose-escalation phase) and may later expand enrollment in selected tumor types once a recommended dose is found.
详细描述
Study Design:
ACC-1898-101 is an open-label, multicenter, interventional Phase 1 study sponsored by AccSalus Biosciences Inc. (IND #177222). The trial evaluates the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity of ACC-1898 in adults with advanced solid tumors that are unresponsive to or ineligible for standard therapies.
Rationale:
Aberrant activation of receptor tyrosine kinases (RTKs) drives tumor proliferation, angiogenesis, and resistance to therapy.
ACC-1898 (also known as ST-1898) is a small-molecule inhibitor designed to block several RTK pathways simultaneously. Nonclinical studies demonstrated broad antitumor activity and favorable oral bioavailability, while early clinical experience (≈ 100 patients in prior Asian trials) showed a manageable safety profile with preliminary efficacy.
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
盲法说明
This is an open-label study; no masking or blinding procedures are applied.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Participants receive ACC-1898 tablets orally once daily (QD) in 21-day cycles
Dose-Escalation (Part 1): Determine the maximum tolerated dose (MTD) and/or optimal biologic dose (OBD) using an Accelerated Titration → Bayesian Optimal Interval (ATD-BOIN) design.
Treatment continues until disease progression, unacceptable toxicity, withdrawal, or study completion
干预措施: ACC-1898 (Drug)
ACC-1898 Dose Expansion Cohorts
Participants will receive ACC-1898 tablets orally once daily (QD) in repeating 21-day cycles at dose levels determined from Part 1 (dose escalation).
This Phase 1b dose-expansion phase will enroll patients with selected advanced or metastatic solid tumors to further characterize the safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of ACC-1898 at the recommended Part 2 dose(s).
Up to three tumor-specific expansion cohorts may be opened. Within each indication, participants may be randomized between two ACC-1898 dose levels that demonstrated acceptable safety and evidence of activity in Part 1.
Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or study completion.
Paired tumor biopsies and optional blood samples will be collected to explore biomarker and PK/PD correlations.
干预措施: ACC-1898 (Drug)
结局指标
主要结局
Incidence of Dose-Limiting Toxicities (DLTs) Part 1 (Dose Escalation)
时间窗: Cycle 1 (each cycle = 21 days)
Occurrence of DLTs within the first treatment cycle to determine the maximum tolerated dose (MTD) and/or recommended Part 2 dose (OBD).
Treatment-Emergent Adverse Events (TEAEs)
时间窗: From first dose through 28 days after last dose (up to 2 years)
Incidence, severity, and relationship of TEAEs graded per CTCAE v5.0.
次要结局
- Maximum Observed Plasma Concentration (Cmax) Part 1 (Pharmacokinetics)(Cycle 1 Day 1 and Day 15 (Cycle length = 21 days))
- Area Under the Concentration-Time Curve (AUC₀-last) Part 1 (Pharmacokinetics)(Cycle 1 Day 1 and Day 15 (Cycle length = 21 days))
- AUC₀-τ (steady-state interval) Part 1 (Pharmacokinetics)(Cycle 1 Day 15 (Cycle length = 21 days))
- AUC₀-∞ Part 1 (Pharmacokinetics)(Cycle 1 Day 1 (Cycle length = 21 days))
- Terminal Half-Life (t½) Part 1 (Pharmacokinetics)(Cycle 1 Day 1 and Day 15 (Cycle length = 21 days))
- Apparent Oral Clearance (CL/F) Part 1 (Pharmacokinetics)(Cycle 1 Day 15 (Cycle length = 21 days))
- Apparent Volume of Distribution (Vz/F) Part 1 (Pharmacokinetics)(Cycle 1 Day 15 (Cycle length = 21 days))
- Minimum Observed Plasma Concentration (Cmin) Part 1 (Pharmacokinetics)(Cycle 1 Day 15 (Cycle length = 21 days))
- Accumulation Ratio for AUC (AR-AUC) Part 1 (Pharmacokinetics)(Cycle 1 Day 15 vs Day 1 (Cycle length = 21 days))
- Accumulation Ratio for Cmax (AR-Cmax) Part 1 (Pharmacokinetics)(Cycle 1 Day 15 vs Day 1 (Cycle length = 21 days))