Phase Ib Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of HSK41959 Tablets in Combination With Standard Therapy in Patients With MTAP Deletion Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 258
- 试验地点
- 1
- 主要终点
- DLTs
研究概览
简要总结
This is a Phase Ib, open-label, multicenter study of HSK41959 tablets in combination with standard therapy in patients with MTAP-deficient advanced solid tumors. The study consists of dose-escalation and dose-expansion parts and is intended to evaluate the safety, tolerability, dose-limiting toxicity, maximum tolerated dose, pharmacokinetics, pharmacodynamics, and preliminary efficacy of HSK41959 tablets when used together with standard therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Factorial
- 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
- •Adult participants aged 18 years or older.
- •ECOG performance status of 0 to
- •Life expectancy of at least 3 months.
- •Histologically or cytologically confirmed advanced malignant tumor with MTAP deficiency identified by a validated assay.
- •At least one measurable lesion according to RECIST version 1.
- •For NSCLC cohorts: advanced or metastatic NSCLC meeting protocol-specified disease characteristics and prior treatment requirements.
- •For PDAC cohorts: advanced or metastatic PDAC meeting protocol-specified disease characteristics and prior treatment requirements.
- •Adequate bone marrow, hepatic, renal, and coagulation function.
- •Willingness to provide tumor tissue and/or undergo protocol-required biomarker testing, if applicable.
排除标准
- •Prior exposure to agents targeting the MAT2A or PRMT5 pathway.
- •Prior antitumor therapy or unresolved toxicities not meeting protocol-defined washout/recovery requirements.
- •Known actionable driver alterations or prior therapies excluded by the protocol for specific NSCLC cohorts (for example EGFR, ALK, ROS1, BRAF, NTRK, MET, RET, KRAS G12C, HER2, as applicable).
- •Significant gastrointestinal disorders that may affect drug absorption.
- •Clinically significant cardiovascular disease, including clinically relevant QTc prolongation, reduced left ventricular ejection fraction, or severe heart failure.
- •Uncontrolled metabolic disease, uncontrolled hypertension, or active infection.
- •Known HIV infection, active hepatitis B with significant viral replication, or active hepatitis C infection.
- •Use of prohibited concomitant medications, including strong inhibitors or inducers of CYP3A4, P-gp, BCRP, or other protocol-specified transporters/enzymes within the required washout period.
- •Other serious medical or psychiatric conditions that, in the investigator's judgment, would make study participation inappropriate.
研究组 & 干预措施
Dose-Escalation Arm
干预措施: Sintilimab (Drug)
Dose-Expansion First-line PDAC cohort
干预措施: Nab-paclitaxel + Gemcitabine (Drug)
Dose-Escalation Arm
干预措施: HSK41959 (Drug)
Dose-Escalation Arm
干预措施: Pemetrexed + Cisplatin /Carboplatin (Drug)
Dose-Escalation Arm
干预措施: Paclitaxel + Carboplatin (Drug)
Dose-Escalation Arm
干预措施: Nab-paclitaxel + Carboplatin (Drug)
Dose-Expansion：First-line NSCLC cohort
干预措施: Nab-paclitaxel + Carboplatin (Drug)
Dose-Expansion：First-line NSCLC cohort
干预措施: Sintilimab (Drug)
Dose-Expansion：First-line NSCLC cohort
干预措施: Pemetrexed + Cisplatin /Carboplatin (Drug)
Dose-Expansion：First-line NSCLC cohort
干预措施: Paclitaxel + Carboplatin (Drug)
Dose-Expansion Second-line NSCLC cohort
干预措施: HSK41959 (Drug)
Dose-Expansion Second-line NSCLC cohort
干预措施: Docetaxel (Drug)
Dose-Expansion：First-line NSCLC cohort
干预措施: HSK41959 (Drug)
Dose-Expansion First-line PDAC cohort
干预措施: HSK41959 (Drug)
结局指标
主要结局
DLTs
时间窗: 21 days for NSCLC cohorts; 28 days for PDAC cohorts
DLTs assessed during the protocol-defined DLT evaluation period.
AEs
时间窗: Up to approximately 3 years
Rate and severity of adverse events of HSK41959 Tablets in Combination With Standard Therapy
次要结局
- Overall response rate (ORR)(Up to approximately 3 years)
- Disease control rate (DCR)(Up to approximately 3 years)
- Progression free survival (PFS)(Up to approximately 3 years)
- Overall survival (OS)(Up to approximately 3 years)
- Area under the curve (AUC) of HSK41959 Tablets in Combination With Standard Therapy(Up to approximately 6 months)
- maximum plasma concentration (Cmax) of HSK41959 Tablets in Combination With Standard Therapy(Up to approximately 6 months)
- Tmax(Time to maximum plasma concentration) of HSK41959 Tablets in Combination With Standard Therapy(Up to approximately 6 months)