A Phase 1 Study of EP31670, a Dual BET and CBP/p300 Inhibitor in Patients With Targeted Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 6
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
A Phase 1, first-in-human study of EP31670, a dual BET and CBP/p300 inhibitor in patients with targeted advanced solid tumors.
详细描述
EP31670 (also known as NEO2734) is a first-in-class dual BET and CBP/p300 inhibitor which has demonstrated antitumor activity in in vitro and in vivo models of human cancer. This Phase I open-label, multi-center, dose-escalation study will assess the safety and determine the maximum tolerated dose of EP31670 administered orally in patients with castration-resistant prostate cancer, NUT midline carcinoma and other targeted advanced solid tumors.
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
- •Relapse or refractory castration-resistant prostate cancer (CRPC) following at least one anti-androgen regimen and a docetaxel-containing regimen OR
- •metastatic or unresectable NUT midline carcinoma for which standard curative or palliative measures do not exist; OR
- •patients who have other types of relapsed or refractory solid tumors with pathological and/or biological features suggesting a potential benefit from dual BET and CBP/p300 inhibition may be enrolled after discussion with and approval from medical monitor and sponsor
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •Life expectancy ≥ 3 months
- •Evaluable disease
- •Adequate bone marrow function:
- •Hemoglobin ≥ 9.0 g/dL Absolute neutrophil count (ANC) ≥ 1,500/dL Platelet count ≥100,000/μL
- •Adequate renal function:
- •Creatinine clearance (CLcr) estimated by Cockcroft-Gault Equation to be ≥ 60 mL/min. Estimated glomeruli filtration rate (eGRF) ≥ 60 mL/min may be used if provided by the testing laboratory
- •Adequate liver function
- •Total bilirubin ≤ 1.5 x ULN except in patients diagnosed with Gilbert's disease for which direct bilirubin must be ≤ 1.5 x ULN
- •Alanine aminotransferase (ALT) or aspartate Aminotransferase (AST) ≤ 2.5 x ULN or ≤ 5 x ULN in patients with liver metastases
- •Internal normalized ratio for prothrombin time (INR) ≤ 1.2 in patients not receiving chronic anticoagulation
- •Four weeks from prior anti-cancer therapy including chemotherapy, immunotherapy, investigational anti-cancer therapy or 5 half-lives from targeted agents, radiation and have recovered from prior treatment toxicities to grade 1 or less. Prostate cancer patients may continue androgen-deprivation therapy by luteinizing hormone-releasing hormone (LHRH) agonists.
- •Four weeks from major surgery.
- •For fertile men and women, agreement to use effective contraceptive methods duration of study participation and 4 weeks after the last dose of study drug.
- •Ability to understand and willingness to sign the informed consent form.
排除标准
- •New and progressive central nervous system (CNS) metastasis; patients with treated brain metastases are eligible if follow-up brain imaging at least 4 weeks after CNS-directed therapy shows no evidence of progression and the patient is neurologically stable
- •Corrected QT interval ≥470 msec
- •Uncontrolled concurrent illnesses including, but not limited to, ongoing active infection requiring intravenous antibiotics or antifungal agents, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness/social situations that would affect compliance with study requirements; patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of EP31670 are eligible for this trial
- •Pregnant or lactating women
- •Known history of hepatitis B, hepatitis C requiring antiviral treatment
- •Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
研究组 & 干预措施
Part 1
Patients will be assigned escalated dose according to BOIN design. The starting dose is 5 mg orally once a day for 7 consecutive days followed by 14 days of rest.
干预措施: EP31670 (Drug)
Part 2
Patients will be assigned escalated dose according to BOIN design. The starting dose is 20 mg orally once a day for 14 consecutive days followed by 14 days of rest.
干预措施: EP31670 (Drug)
Part 3
Patients will be assigned escalated dose according to BOIN design. The starting dose is 10 mg orally once a day for 14 consecutive days in combination with ruxolitinib or momelotinib followed by 14 days of rest according to the traditional 3 + 3 design by the modified Fibonacci sequence
干预措施: EP31670 (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: Within 3 weeks (one cycle) of treatment
MTD is the highest dose level at which ≤30% of patients experienced DLTs during cycle 1.
Dose Limiting Toxicities (DLT)
时间窗: Within 3 weeks (one cycle) of treatment
DLT is any of the following adverse events (AEs) that occur during cycle 1.
Recommended Phase 2 Dose (RP2D)
时间窗: through study completion, an average of 1 year
RP2D will be the MTD
次要结局
未报告次要终点