A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of CS23546 in Subjects With Advanced Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 156
- 试验地点
- 1
- 主要终点
- Dose Limiting Toxicities (DLTs)
研究概览
简要总结
The primary objectives of this study are to characterize the safety and tolerability of CS23546 and to evaluate the pharmacokinetic (PK) characteristics and recommended phase 2 dose (RP2D) of CS23546 in subjects with advanced tumors.
详细描述
This study is a single arm, open phase I trial, consisting of a dose escalation phase (single dose+multiple doses) and a dose expansion phase, accompanied by pharmacokinetic and pharmacokinetic studies. The first visit period (21 days) of single dose and multiple doses during the dose-increasing phase is the DLT observation period.
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
- •Male or female and ≥18 years of age on day of signing informed consent.
- •Histologically or cytologically confirmed unresectable advanced recurrent/refractory solid tumor or lymphoma that is failure or or intolerant of all standard therapy or for which no standard therapy is available.
- •Individuals are required to provide tumor tissue samples for prospective detection of Programmed cell death 1 ligand 1 (PD-L1) expression and/or Microsatellite instability (MSI) / the DNA mismatch repair (MMR) status. Subjects who cannot be provided during the dose escalation phase will be evaluated by the researchers and sponsors before deciding whether to enroll.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or
- •Adequate organ function.
- •Life expectancy ≥12 weeks.
- •Dose expansion phase: Cohort 1, Subjects with urothelial carcinoma. Cohort 2, Subjects with Extranodal NK/T-cell lymphoma (NKTCL). Cohort 3, Subjects with soft tissue sarcoma. Cohort 4, Subjects with PD-L1 expression positive and/or microsatellite-instability-high (MSI-H) / mismatch-repair-deficient (dMMR) advanced solid tumors or lymphoma
排除标准
- •Received anti-tumor therapy (including but not limited to chemotherapy, targeted therapy, anti angiogenic therapy, immunotherapy, cell therapy, radiotherapy, tumor embolization, etc.) or experimental drugs/devices that have not been approved for marketing within 28 days before the first medication.
- •History of ≥ Grade 3 immune related Adverse Events (irAEs) or termination of treatment due to irAEs during prior treatment with Programmed death 1 (PD-1) /PD-L1 antibody.
- •Active autoimmune diseases present during the screening period and systemic treatment was received within 2 years before the first medication. Individuals who only require hormone replacement therapy (such as thyroxine, insulin, or physiological corticosteroids used for adrenal or pituitary insufficiency) can be enrolled.
- •Presence of central nervous system metastasis and/or meningeal metastasis.
- •Dose expansion phase: Subjects with solid tumors or lymphoma who have previously received PD-L1 inhibitors and belong to primary resistance.
研究组 & 干预措施
Dose escalation
Single ascending dose (SAD): Participants will receive CS23546 once on the first day (D1).
Multiple ascending dose (MAD): Participants will receive CS23546 once daily from the 7th day (C1D1).
干预措施: CS23546 (Drug)
Dose expansion
Dose expansion is planned to begin when the recommended Phase 2 dose (RP2D) will be determined.
干预措施: CS23546 (Drug)
结局指标
主要结局
Dose Limiting Toxicities (DLTs)
时间窗: Day 1 through Day 27
DLT: Number of patients experienced any dose limited toxicity. MTD: One level lower than the dose level at which dose escalation was terminated due to DLT reasons.
Time to Cmax (Tmax)
时间窗: up to Day 1 of cycle 5 (each cycle is 21 days)
Time to reach the Cmax for CS23546.
Maximum Tolerated Dose (MTD)
时间窗: Day 1 through Day 27
MTD: One level lower than the dose level at which dose escalation was terminated due to DLT reasons.
Maximum plasma concentration (Cmax)
时间窗: up to Day 1 of cycle 5 (each cycle is 21 days)
Maximum observed plasma concentration for CS23546.
Area Under the Curve (AUC)
时间窗: up to Day 1 of cycle 5 (each cycle is 21 days)
Area Under the Plasma Concentration-time Curve From Zero Time to the Last Measurable Point for CS23546.
次要结局
- Disease control rate (DCR)(Until 28 days after the last dose of the study drug)
- Duration of response (DOR)(Until 28 days after the last dose of the study drug)
- Time to progression (TTP)(Until 28 days after the last dose of the study drug)
- time to progressive disease (TTR)(Until 28 days after the last dose of the study drug)
- Progression free survival (PFS)(Until 28 days after the last dose of the study drug)
- The inhibitory activity of Programmed cell death 1 ligand 1 (PD-L1)(up to Day 1 of cycle 5 (each cycle is 21 days))
- Interferon gamma (IFN-γ)(up to Day 1 of cycle 5 (each cycle is 21 days))
- Free PD-L1(up to Day 1 of cycle 5 (each cycle is 21 days))
- C-X-C motif chemokine 9 (CXCL9)(up to Day 1 of cycle 5 (each cycle is 21 days))
- C-X-C motif chemokine 10 (CXCL10)(up to Day 1 of cycle 5 (each cycle is 21 days))
- Objective response rate (ORR)(Until 28 days after the last dose of the study drug)
- Overall survival (OS)(Until 28 days after the last dose of the study drug)
- Safety indicators: adverse events (AE)(Until 28 days after the last dose of the study drug)