A Phase 1/2, Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Chaperone-mediated Protein Degrader RNK05047 in Subjects With Advanced Solid Tumors (CHAMP-1)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 32
- 试验地点
- 5
- 主要终点
- Part 1: Incidence of DLTs
研究概览
简要总结
This is a first in human, Phase 1/2 open-label multi-center, dose escalation and expansion study to evaluate the safety, tolerability, PK, PD and efficacy of RNK05047 when administered an intravenous (IV) infusion to subjects with advanced solid tumors, including diffuse large B-cell lymphoma (DLBCL).
This is a 2-part study (dose escalation, cohort expansion) with sequential enrollment.
详细描述
In Part 1, enrolled subjects will receive IV RNK05047 once weekly for 3 consecutive weeks in a 4-week cycle (no treatment in the fourth week). The dose-escalation phase will follow a standard 3+3 design, with 3 subjects enrolled into the first dosing cohort to receive RNK05047 at the starting dose of 0.75 mg/kg.
In Part 2, once RP2D has been established, additional subjects (3 to 5 cohorts of approximately 15 subjects per cohort) will be enrolled in the cohort-expansion phase of the study. Tumor types for these cohorts will be determined based on data from the dose-escalation phase of the study and emerging results from preclinical studies or other scientific data. These dose expansion cohorts in all groups may be done concurrently.
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
- •Pathologically documented locally advanced or metastatic solid tumor
- •Refractory or intolerant to all available standard-of-care therapies for advanced disease
- •Measurable disease
- •Archived tumor tissue collected
- •ECOG Performance Status of 0 or 1
- •BMI ≥ 18 kg/m2
- •Adequate liver, renal, hematologic, and coagulation parameters
- •Negative serum pregnancy test (for women of childbearing potential) at Screening and a negative urine or serum pregnancy test on Day 1 prior to the first infusion
- •Males and females of childbearing potential must agree to use a highly effective method of contraception during treatment and for at least 4 months after the last dose of study treatment.
- •Must be able to understand and comply with the conditions of the protocol and must have read and understood the consent form and provided written informed consent.
排除标准
- •Concurrent anticancer therapy: Radiotherapy, chemotherapy, biological therapy, or other anticancer investigational agents NOTE: at least 5 half-lives must have been ensued for any prior systemic cancer therapy agent before subject received the study drug on Day 1
- •Unresolved toxicities from prior anticancer therapy, defined as not having resolved according to CTCAE version 5.0 Grade ≤ 1, excluding Grade 1 alopecia
- •Presence or suspicion of active central nervous system (CNS) metastases and/or leptomeningeal carcinomatosis
- •Peripheral neurotoxicity ≥ Grade 2 according to CTCAE v5.0
- •Known active infection with HIV, HTLV-1, hepatitis B or C
- •Women who are pregnant or breastfeeding
- •History of another malignancy unless the subject has been treated with curative intent for this malignancy
研究组 & 干预措施
RNK05047
Dose-escalation of RNK05047 IV infusion
干预措施: RNK05047 (Drug)
结局指标
主要结局
Part 1: Incidence of DLTs
时间窗: through 1 cycle/4 weeks
Part 2: Incidence of TEAEs
时间窗: through study completion, an average of 1 year
Part 1: Incidence of TEAEs
时间窗: through study completion, an average of 1 year
Part 2: Objective response rate (ORR) based on RECIST 1.1/RECIL 2017
时间窗: through study completion, an average of 1 year
Part 2: Duration of response (DoR) based on RECIST 1.1/RECIL 2017
时间窗: through study completion, an average of 1 year
Part 2: Disease Control Rate (DCR) based on RECIST 1.1/RECIL 2017
时间窗: through study completion, an average of 1 year
Part 2: Progression-free Survival (PFS) based on RECIST 1.1/RECIL 2017
时间窗: through study completion, an average of 1 year
次要结局
- Part 1: ORR based on RECIST 1.1/RECIL 2017(through study completion, an average of 1 year)
- Part 2: Overall Survival (OS)(through study completion, an average of 1 year)
- Part 2: Plasma concentration RNK05047(Through Cycle 3/approximately 12 weeks)
- Part 1: PFS based on RECIST 1.1/RECIL 2017(through study completion, an average of 1 year)
- Part 1: Plasma concentration RNK05047(Through Cycle 3/approximately 12 weeks)
- Part 1: DoR based on RECIST 1.1/RECIL 2017(through study completion, an average of 1 year)
- Part 1: DCR based on RECIST 1.1/RECIL 2017(through study completion, an average of 1 year)