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
- 2 期
- 状态
- 招募中
- 入组人数
- 31
- 试验地点
- 27
- 主要终点
- Phase 1b and Phase 2: Frequency and severity of adverse events (AEs) and laboratory abnormalities according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v5.0).
研究概览
简要总结
Phase 1b (safety lead in part): To evaluate the safety and tolerability of the combination and to identify the recommended Phase 2 dose (RP2D) of S095029 in combination therapy.
Phase 2:
- To evaluate the antitumor activity of S095029 in combination therapy
- To evaluate the safety and tolerability profile of S095029 in combination therapy
研究设计
- 分配方式
- Na
- 主要目的
- Phase 2
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Participants must have a histologically or cytologically confirmed diagnosis of a locally advanced and unresectable or metastatic gastric or gastroesophageal 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. This status may be documented in a report in the participant’s medical history or the MSI-H/dMMR status may be documented by testing archival tumor tissue or tissue from a newly collected tumor biopsy (if no appropriate archived specimen is available).
排除标准
- •Has received prior therapy with any checkpoint inhibitor (anti-PD-1, anti-programmed cell death ligand 1 (PDL1), anti-CTLA4).
- •Has received more than one previous line of treatment in the locally advanced and unresectable or metastatic setting. Previous treatment line may include trastuzumab and chemotherapy, or doublet/triplet chemotherapy regimens. Note: participants who have received only one cycle of chemotherapy prior to determination of their tumor’s MSI-H status, and who have not yet been treated with an anti-PD-1/L1 agent are not considered to have had one prior line of treatment. Previous treatment with chemotherapy in the neoadjuvant or adjuvant setting is permitted and is not counted as a previous line of therapy for the purpose of determining a patient’s eligibility.
- •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 or have had a history of radiation pneumonitis. Participants who have not recovered from all radiation-related toxicities and require corticosteroids. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
- •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
KEYTRUDA 25 mg/mL concentrate for solution for infusion
干预措施: KEYTRUDA 25 mg/mL concentrate for solution for infusion (Drug)
S095029/Sym025
干预措施: S095029/Sym025 (Drug)
结局指标
主要结局
Phase 1b and Phase 2: Frequency and severity of adverse events (AEs) and laboratory abnormalities according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v5.0).
Phase 1b and Phase 2: Frequency and severity of adverse events (AEs) and laboratory abnormalities according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v5.0).
Phase 1b and Phase 2: Incidence of dose-limiting toxicities (DLTs).
Phase 1b and Phase 2: Incidence of dose-limiting toxicities (DLTs).
Phase 1b and Phase 2: Change from baseline to the end of the study in safety laboratory values and vital signs.
Phase 1b and Phase 2: Change from baseline to the end of the study in safety laboratory values and vital signs.
Phase 1b and Phase 2: Incidence of AEs leading to dose interruption, modification, delays and permanent treatment discontinuation.
Phase 1b and Phase 2: Incidence of AEs leading to dose interruption, modification, delays and permanent treatment discontinuation.
Phase 2: Objective response (OR) per investigator assessment using RECIST v1.1.
Phase 2: Objective response (OR) per investigator assessment using RECIST v1.1.
次要结局
- Phase 2: DoR, PFS, and DC according to RECIST v1.1 as assessed by investigator.
- Phase 2: OR, DoR, PFS, and DC according to iRECIST criteria as per investigator assessment.
- Phase 1b: Objective response (OR), duration of response (DoR), progression-free survival (PFS), and disease control (DC) according to RECIST v1.1 and iRECIST as assessed by investigator.
- Phase 1b and Phase 2: Overall survival (OS) per investigator assessment.
- Phase 1b and Phase 2: Serum concentrations of S095029
- Phase 1b and Phase 2: Concentration of potential antibodies directed against S095029.
研究者
Clinical Studies Department
Scientific
Institut De Recherches Internationales Servier IRIS