A Phase 1/2 Study of CLIO-8221 in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 306
- 试验地点
- 11
- 主要终点
- Type, incidence, severity, and seriousness of adverse events (AEs)
研究概览
简要总结
The study will be conducted in 2 phases: Phase 1: Dose-escalation and Dose Level Expansion, Phase 1 will determine the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE). Phase 2: Tumor-Specific Expansions with Dose Optimization, Phase 2 will further evaluate CLIO-8221 in tumor-specific expansion cohorts to optimize dosing and assess preliminary efficacy.
详细描述
Phase 1: Dose-escalation and Dose Level Expansion. Dose escalation safety data will be reviewed by a Safety Monitoring Committee (SMC) to guide dosing decisions. Backfill enrollment may be used to further characterize safety, PK/PD, and antitumor activity.
Phase 2: Tumor-Specific Expansions with Dose Optimization. Phase 2 will further evaluate CLIO-8221 in tumor-specific expansion cohorts to optimize dosing and assess preliminary efficacy. Safety, tolerability, PK/PD, and response data will support selection of the recommended Phase 2 dose (RP2D) for further development.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
盲法说明
No, this is an open-label trial
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
- •Patients with advanced solid tumors
- •Patients must have metastatic or unresectable disease not suitable for further local treatment and should have received prior beneficial therapies unless ineligible, unwilling, or lacking access.
- •LVEF ≥50% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan.
- •An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
- •Measurable disease per RECIST version 1.1 at baseline
排除标准
- •Prior anti-tumor treatment with an ATRi.
- •Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Exceptions are malignancies with a negligible risk of metastasis or death (e.g., 5-year OS ≥90%), including, but not limited to, adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, and Stage I uterine cancer.
- •History of uncontrolled seizure disorders or clinically significant neurodegenerative disorders, including progressive peripheral neuropathy. Stable Grade ≤ 2 peripheral neuropathy is allowed.
- •Clinically significant autoimmune disease, either currently present or present within the previous 2 years, including a current requirement for systemic immunosuppressive therapy equivalent to >10 mg/prednisone daily (local immunosuppressive therapy such as inhaled or topical corticosteroids is allowed).
- •Any uncontrolled Grade ≥ 3 (per NCI CTCAE version 6.0) viral, bacterial, or fungal infection within 2 weeks prior to Cycle 1 Day
- •Routine antimicrobial prophylaxis is permitted.
- •History of hepatic cirrhosis, autoimmune hepatitis, or drug-associated hepatitis within the past 12 months.
- •Uncontrolled diabetes mellitus, defined as Hgb A1c ≥8% or Hgb A1c between 7% and <8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained.
- •Any other medical, social, or psychosocial factors that, in the opinion of the investigator, could impact safety or compliance with study procedures.
- •Additional protocol defined inclusion/exclusion criteria may apply
研究组 & 干预措施
Dose escalation and dose level expansion
Phase 1: CLIO-8221 monotherapy in escalating doses. Phase 2: Phase 2 will be initiated in tumor-specific expansion cohorts at selected doses.
干预措施: CLIO-8221 (Drug)
结局指标
主要结局
Type, incidence, severity, and seriousness of adverse events (AEs)
时间窗: Through end of treatment, up to approximately 2 years.
Type, incidence, severity, and seriousness of AEs occurred
Type, incidence, severity, and seriousness of adverse events (AEs)
时间窗: Through end of treatment, up to approximately 2 years.
Type, incidence, severity, and seriousness of AEs occurred
Type, incidence, and severity of laboratory abnormalities
时间窗: Through end of treatment, up to approximately 2 years.
Type, incidence, and severity of laboratory abnormalities occurred
Incidence of dose limiting toxicities dose (RP2D) of CLIO-8221
时间窗: From first dose through study day 21.
Incidence of dose limiting toxicities occurred
次要结局
- Progression-free survival(Up to approximately 2 years.)
- Objective Response Rate(Through disease progression, up to approximately 2 years.)
- Disease control rate(Through disease progression, up to approximately 2 years.)
- Duration of objective response(From the date of enrollment until a confirmed partial or complete response is achieved, assessed up to 2 years.)
- Pharmacokinetic Parameter Area Under the Curve (AUC) for CLIO-8221(Varying timepoints through end of treatment, up to approximately 2 years.)
- Pharmacokinetic Parameter Maximum Concentration (Cmax) for CLIO-8221(Varying timepoints through end of treatment, up to approximately 2 years.)
- Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) for CLIO-8221(Varying timepoints through end of treatment, up to approximately 2 years.)
- Pharmacokinetic Parameter Total Clearance (CL) for CLIO-8221(Varying timepoints through end of treatment, up to approximately 2 years.)
- Pharmacokinetic Parameter Volume of distribution at steady state (Vd) for CLIO-8221(Varying timepoints through end of treatment, up to approximately 2 years.)
- Pharmacokinetic Parameter Apparent Terminal Half-life (t1/2) for CLIO-8221(Varying timepoints through end of treatment, up to approximately 2 years.)