A Phase I/II , Open-label, Multi-center, Multi-cohort Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of HYP-6589 Monotherapy in Advanced Solid Tumors and Combination With Tyrosine Kinase Inhibitors in Patients With Advanced NSCLC With Target-driven Gene Positivity
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 115
- 试验地点
- 1
- 主要终点
- Dose Escalation (Part One): Incidence and Nature of Dose-Limiting Toxicity (DLT)
研究概览
简要总结
This is a multi-center , open-label, phase 1/2 study to evaluate the safety, efficacy, and pharmacokinetic (PK) characteristics of HYP-6589 in monotherapy in advanced solid tumors and combination with tyrosine kinase inhibitors in patients with advanced NSCLC with target-driven gene positivity.
详细描述
The study starts with a dose escalation part (Part 1) followed by a dose expansion part (Part 2). The main purpose of this study is to evaluate the safety and tolerability of the drug HYP-6589 and determine the maximum tolerated dose (MTD) (if any) and/or the recommended dose(s) (RD) and preliminary anti-tumor activity. Additional purposes of the study are to evaluate the pharmacokinetics (PK) properties.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntarily sign an informed consent form, understand the study and be willing and able to follow and complete all trial procedures;
- •≥18 years old and ≤80 years old, gender: male or female;
- •Histological or cytological confirmation of unresectable and/or metastatic advanced solid tumors;
- •At least one measurable lesion (according to RECIST 1.1 version);
- •Eastern Cooperative Oncology Group (ECOG) performance status score is 0 or 1;
- •Life expectancy ≥3 months;
- •Participant must have adequate main organ function;
- •Fertile female patients must have a negative serological pregnancy test within 7 days before the first dosing and be willing to use effective birth control/contraception to prevent pregnancy during the study period up to 6 months after the last dosing of the study. Male patients must agree to have no sperm donation plans and to use effective contraceptive methods during the study period until 6 months after the last dose of the study. Postmenopausal women must have amenorrhea for at least 12 months before they are considered infertile.
排除标准
- •Participants who have received other investigational drugs or participated in interventional medical device studies within 4 weeks prior to the first administration of the study drug;
- •Participants who have received (attenuated) live vaccines within 4 weeks prior to the first administration of the study drug;
- •Participants who have undergone major organ surgery (excluding biopsy) within 4 weeks prior to the first administration of the study drug or have experienced significant trauma, or who require elective major organ surgery (excluding biopsy) during the study period;
- •Participants who, based on computerized tomography (CT) or magnetic resonance imaging (MRI) examinations conducted during the screening period and before radiological assessment, have uncontrolled, unstable, or active central nervous system (CNS) metastases;
- •Participants with clinically uncontrollable hypertension (defined in this protocol as having a systolic blood pressure > 150 mmHg and/or a diastolic blood pressure > 100 mmHg despite antihypertensive treatment, and which is considered clinically significant by the investigator);
- •Participants who have received allogenic tissue/organ transplants in the past;
- •Participants with active infections deemed inappropriate for entry into the study by the investigator;
- •Participants with uncontrolled third-space effusion requiring clinical intervention;
- •Participants with a history of drug abuse or medical, psychological, or social conditions that may interfere with study participation or impair the assessment of study outcomes;
- •Participants with known gastrointestinal (GI) dysfunction or GI diseases that are likely to significantly affect the absorption or metabolism of oral medications (e.g., dysphagia, active upper gastrointestinal ulcer, intestinal obstruction, nausea, vomiting, and diarrhea of grade 3 or higher that persist despite optimal supportive care within 3 days);
- •Participant whose toxicities from previous anti-cancer therapy have not resolved, defined as toxicity (hair loss excluded) that has not resolved to grade ≤1 (CTCAE 5.0 version, peripheral neuropathy, ≤grade 2; exclusion criteria specified);
- •Female participants who are breastfeeding or have positive urine or blood pregnancy test results during the screening period; female participants who have a planned pregnancy, sperm donation, or egg donation during the study period or within 6 months after the last study drug administration;
- •Known history of hypersensitivity to any of the components of the test formulation.
- •Participants who have had other malignancies within the past 5 years, excluding cured cervical carcinoma in situ, basal cell carcinoma of the skin or squamous cell carcinoma of the skin;
研究组 & 干预措施
Test product HYP-6589
HYP-6589 should be administered orally at the recommended dosage
干预措施: Test Product HYP-6589 (Drug)
结局指标
主要结局
Dose Escalation (Part One): Incidence and Nature of Dose-Limiting Toxicity (DLT)
时间窗: 24 days during the first 4-week cycle
Dose-Limiting Toxicity (DLT) will be defined using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Dose Escalation (Part One): Percentage of participants experiencing treatment-emergent adverse events (TEAEs)
时间窗: Up to 2 years
Incidence and severity of adverse events (AEs), serious adverse events (SAEs), and lab abnormalities, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
Dose Escalation (Part One): Other safety indicators
时间窗: Up to 2 years
Adverse events (AE), physical examination, vital signs, electrocardiogram (ECG) and laboratory test results that occur during the treatment
Dose Expansion (Part Two): Objective Response Rate (ORR)
时间窗: Up to 2 years
Proportion of participants who have a confirmed Complete Response (CR) or a Partial Response (PR)
次要结局
- Dose Expansion (Part Two): Percentage of participants experiencing treatment-emergent adverse events (TEAEs)(Up to 2 years)
- Dose Expansion (Part Two): Other safety indicators(Up to 2 years)
- Dose Escalation and Expansion: Assessment of HYP-6589 Cmax(Up to 2 years)
- Dose Escalation and Expansion: Assessment of HYP-6589 AUC(Up to 2 years)
- Dose Escalation and Expansion: Assessment of HYP-6589 T1/2(Up to 2 years)
- Dose Escalation (Part One): Objective Response Rate (ORR)(Up to 2 years)
- Dose Escalation and Expansion: Duration Of Response (DOR) assessed by investigator per Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1(Up to 2 years)
- Dose Escalation and Expansion: Disease Control Rate (DCR) assessed by investigator per RECIST Version 1.1(Up to 2 years)
- Dose Escalation and Expansion: Progression-Free Survival (PFS) assessed by investigator per RECIST Version 1.1(Up to 2 years)
- Dose Escalation and Expansion: Overall Survival (OS)(Up to 2 years)