A Study of a Mutant-Selective Inhibitor, CGT6297, in Patients With Advanced Solid Tumors Harboring PIK3CA Mutations
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 90
- 试验地点
- 4
- 主要终点
- Incidence and grade of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Phase 1a]
研究概览
简要总结
This is a Phase 1, two-part, open-label, nonrandomized, dose-escalation and signal-seeking study of CGT6297, evaluating the safety, tolerability, PK, pharmacodynamic (what the drug does to the body), and antitumor activity of CGT6297 in adult participants with advanced solid tumors harboring PIK3CA mutations
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
- •Histologically confirmed advanced solid tumor harboring oncogenic PIK3CA mutations in blood and/or tumor:
- •Phase 1b Cohort 1, participants must have PIK3CA endometrial cancer
- •Phase 1b Cohort 2, participants must have HR-positive/HER2-negative or HER2-low breast cancer (immunohistochemistry [IHC] and in-situ hybridization results must meet ASCO-College of American Pathology guidelines for breast cancer or criteria)
- •Phase 1b Cohort 3 will allow all solid tumors that do not meet criteria for Phase 1b Cohorts 1 or 2, including head and neck cancers, other gynecological cancers, colorectal cancers harboring PIK3CA mutations
- •Meet prior treatment requirement of:
- •Phase 1a: previously treated with and refractory to or intolerant of existing therapy(ies) known to provide clinical benefit for their condition.
- •Phase 1b: previously treated with or considered not appropriate for SOC first-line treatment for their condition
- •Have at least one measurable lesion according to RECIST v1.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1
- •Have clinically acceptable local laboratory screening results (clinical chemistry and hematology) within certain limits
- •Resolution of acute toxicities from prior anticancer therapy to ≤Grade 1 (or baseline), including resolution of clinically significant laboratory abnormalities (other than parameters specified in screening testing as outlined below), as determined by the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCICTCAE) v5.
- •Have an ejection fraction ≥50%
排除标准
- •Received small molecule chemotherapy or anticancer therapies or radiotherapy within certain timeframes before first dose of study drug.
- •Major surgeries (eg, abdominal laparotomy) within 4 weeks of the first dose of study drug
- •Treatment with radiotherapy ≤2 weeks before the first dose of study drug.
- •Clinically significant cardiac disease
- •Ongoing or planned long-term (≥4 consecutive weeks) treatment with glucocorticoid steroids at greater than physiologic dosing (defined as equivalent to >20 mg/day prednisone)
- •Diagnosis of diabetes mellitus type 1 or uncontrolled diabetes mellitus type 2 (defined as fasting glucose ≥140 mg/dL and HbA1c ≥7.0%; antihyperglycemic medical management permitted with the exception of insulin)
- •Previous molecular testing (NGS or PCR) showed tumor with the following mutations: mutations/deletions in PTEN or activating mutations in AKT, HRAS/KRAS/NRAS, EGFR, and BRAF
研究组 & 干预措施
Dose Escalation
Part 1a: Dose Escalation of Multiple doses of CGT6297 for oral administration
干预措施: CGT6297 (Drug)
Signal Seeking
Phase 1b: Participants will receive CGT6297 at a dose level selected based on data from Phase 1a
干预措施: CGT6297 (Drug)
结局指标
主要结局
Incidence and grade of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Phase 1a]
时间窗: Approximately 12 months
Incidence and grade of Adverse Events (AEs) and Serious Adverse Events (SAEs) and AEs leading to dose modifications and dose limiting toxicities (DLTs) to determine the maximum tolerated dose (MTD) or the maximum evaluated dose (MED) of CGT6297 in participants with advanced solid tumors harboring PIK3CA mutations
Overall Response Rate [Phase 1b]
时间窗: Approximately 8 months
Overall Response Rate (ORR), as determined by CR + PR based on Investigator assessment using RECIST v1.1
次要结局
- Incidence and grade of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Phase 1b](Approximately 12 months)
- Pharmacokinetics (Part 1a)(Approximately 28 days)
- Disease Response (Part 1b)(Approximately 8 months)
- Disease Response (Part 1b)(Approximately 28 days)