Open Label, Non-randomized, Phase 1b/2 Trial Investigating the Safety, Tolerability, and Antitumor Activity of S095029 (Anti-NKG2A Antibody) as a Part of Combination Therapy in Participants With Locally Advanced and Unresectable or Metastatic MSI-H/dMMR Gastro-esophageal Junction /Gastric Cancer
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 48
- 试验地点
- 49
- 主要终点
- Number of Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
This study will investigate the safety, tolerability, and antitumor activity of S095029 (anti-NKG2A antibody) in combination with pembrolizumab in in microsatellite instability-high/Defective mismatch repair (MSI-H/dMMR) locally advanced unresectable or metastatic gastric /GEJ adenocarcinomas.
详细描述
This Phase 1b/2 study will be conducted in two parts; a safety lead-in part (Phase 1b) to identify the RP2D of S095029 in combination with pembrolizumab and an expansion part (Phase 2) to evaluate anti-tumor activity and safety in participants with locally advanced unresectable or metastatic MSI-H/dMMR gastric /GEJ adenocarcinomas.
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
- •Have a confirmed diagnosis of locally advanced and unresectable or metastatic gastric or gastro-esophageal junction adenocarcinoma
- •Participants' tumor must have an MSI-H/dMMR status according to institutional guidelines and/or according to the College of American Pathologists, determined at any time prior to enrolment.
排除标准
- •Has received more than one previous line of treatment in the locally advanced and unresectable or metastatic setting.
- •Has received prior therapy with any checkpoint inhibitor (anti-PD-1, anti-programmed cell death ligand 1 (PDL1), anti-CTLA4).
- •Participants who have received prior systemic anti-cancer therapy including investigational agents within 4 weeks (shorter interval, at least 5 half-lives, for kinase inhibitors or other short half-life drugs) prior to first study treatment.
- •Prior radiotherapy if completed less than 2 weeks before first study treatment
- •Major surgery less than 4 weeks prior to the first study treatment or participants who have not recovered from the side effects of the surgery.
研究组 & 干预措施
S095029 and pembrolizumab
Participants diagnosed with gastric cancer (GC) or gastroesophageal junction cancer (GEJ), not previously treated with checkpoint inhibitors (CPIs) may first be enrolled into a Phase 1b safety lead-in part which will be used to identify the recommended Phase 2 dose (RP2D) of S095029 in combination with pembrolizumab. During the Phase 2 part, participants will receive the recommended Phase 2 dose (RP2D) of S095029, along with pembrolizumab.
干预措施: S095029 (Drug)
S095029 and pembrolizumab
Participants diagnosed with gastric cancer (GC) or gastroesophageal junction cancer (GEJ), not previously treated with checkpoint inhibitors (CPIs) may first be enrolled into a Phase 1b safety lead-in part which will be used to identify the recommended Phase 2 dose (RP2D) of S095029 in combination with pembrolizumab. During the Phase 2 part, participants will receive the recommended Phase 2 dose (RP2D) of S095029, along with pembrolizumab.
干预措施: pembrolizumab 200 mg (KEYTRUDA ®) (Drug)
结局指标
主要结局
Number of Dose-Limiting Toxicities (DLTs)
时间窗: At the end of Cycle 1 (each cycle is 21 days)
Phase 1b and Phase 2
Total Number of Adverse Events (AEs)
时间窗: From screening to 90 days after the last dose
Phase 1b and Phase 2
Adverse Events (AEs) Leading to Dose Interruption, Modification, or Delays
时间窗: From screening to 90 days after the last dose
Phase 1b and Phase 2
Adverse Events (AEs) Leading to Dose Discontinuation
时间窗: From screening to 90 days after the last dose
Phase 1b and Phase 2
Objective Response Rate (ORR)
时间窗: Approximately 2 years
Phase 2 ONLY. The Proportion of participants who achieve complete response (CR) or partial response (PR), as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
次要结局
- Trough Concentrations of S095029 (Ctrough)(From first dose to 30 days after the last dose)
- Duration of Response (DoR)(Approximately 2 years)
- Overall Survival (OS)(Approximately 2 years)
- Progression-Free Survival (PFS)(Approximately 2 years)
- Disease Control Rate (DCR)(Approximately 2 years)
- Concentration of potential antibodies directed against S095029(From screening to 30 days after the last dose, or end of study if clinically indicated)
- Objective Response Rate (ORR)(Approximately 2 years)