A Phase 1, Open-Label, Multicenter, Dose Escalation Study of PRT1419 in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 6
- 主要终点
- Dose limiting toxicities (DLT) of PRT1419
研究概览
简要总结
This is a Phase 1 dose-escalation study of PRT1419, a myeloid cell leukemia 1 (MCL1) inhibitor, in patients with advanced solid tumors. The purpose of this study is to define the dosing schedule, maximally tolerated dose and/or estimate the optimal biological dose to be used in subsequent development of PRT1419.
详细描述
This is a multicenter, open-label, dose-escalation Phase 1 study of PRT1419, a MCL1 inhibitor, evaluating patients with relapsed or refractory solid tumors, including breast, lung, sarcoma and melanoma as part of a 28-day treatment cycle. The study will employ a "3+3" dose escalation design. The dose may be escalated until a dose limiting toxicity is identified.
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
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
- •Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
- •Adequate organ function (bone marrow, hepatic, renal, cardiovascular)
- •Left ventricular ejection fraction of ≥ 50%
- •Female patients of childbearing potential must have a negative pregnancy test within 7 days of the start of treatment and must agree to use a highly effective method of contraception during the trial
- •Patients must have recovered from the effects of any prior cancer related therapy, radiotherapy or surgery (toxicity ≤ Grade 1)
- •All patients on prior investigational agents must wait at least 5 half-lives of the agent in question, or 28 days, whichever is longer before study entry
- •Most recent lab values meet the following criteria:
- •Absolute neutrophil count > 1.0 x 10^3/μL;
- •Platelet count > 75,000/μL;
- •Hemoglobin > 9.0 g/dL
- •Histologically confirmed advanced or metastatic solid tumor indicated below that is relapsed, refractory, or intolerant to available therapies with known benefit:
- •Sarcoma not amendable to curative treatment with surgery or radiotherapy;
- •Melanoma (non-resectable or metastatic);
- •Small cell lung cancer (extensive-stage);
- •Non-small cell lung cancer;
- •Triple negative breast cancer (histopathologically or cytologically confirmed).
- •Esophageal cancer
- •Cervical cancer
- •Head and neck cancer
排除标准
- •Known hypersensitivity to any of the components of PRT1419
- •Primary malignancies of the CNS, or uncontrolled CNS metastases, including impending spinal cord compression
- •Female patients who are pregnant or lactating
- •Inflammatory disorders of the gastrointestinal tract, or subjects with GI malabsorption
- •Mean QTcF interval of >480 msec
- •History of heart failure, additional risk factors for arrhythmias or requiring concomitant medications that prolong the QT/QTc interval
- •HIV positive; known active hepatitis B or C
- •Uncontrolled intercurrent illnesses
- •Treatment with strong inhibitors of CYP2C8
- •Prior exposure to an MCL1 inhibitor
- •History of another malignancy except:
- •Malignancy treated with curative intent with no known active disease for >2 years at study entry;
- •Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease;
- •Adequately treated carcinoma in situ without evidence of disease;
- •Other concurrent low-grade malignancies (i.e chronic lymphocytic leukemia (Rai 0)) may be considered after consultation with Sponsor.
研究组 & 干预措施
PRT1419
PRT1419 will be administered by intravenous infusion
干预措施: PRT1419 (Drug)
结局指标
主要结局
Dose limiting toxicities (DLT) of PRT1419
时间窗: Baseline through Day 28
Dose limiting toxicities will be evaluated through the first cycle
Maximally tolerated dose (MTD) and/or optimal biological dose (OBD)
时间窗: Baseline through approximately 2 years
The MTD and/or OBD will be established for further investigation in participants with advanced solid tumors.
Recommended phase 2 dose (RP2D) and schedule of PRT1419
时间窗: Baseline through approximately 2 years
The RP2D will be established for further investigation in participants with advanced solid tumors.
次要结局
- Safety and tolerability of PRT1419: AEs, SAEs, CTCAE assessments(Baseline through approximately 2 years)
- Pharmacokinetic profile of PRT1419: maximum observed plasma concentration(Baseline through approximately 2 years)
- Anti-tumor activity of PRT1419: measurement of objective responses(Baseline through approximately 2 years)
- Progression-free survival(Baseline through approximately 2 years)