A Phase Ib/II Open Label,Dose Escalation and Dose Extension Study Evaluating the Safety, Tolerability, and Initial Antitumor Efficacy of Anti-PD-1 and Lymphocyte Activation Gene 3(LAG-3) Bispecific Antibody AK129 Combined With Chemotherapy With or Without Cadonilimab in Patients With Human Epidermal Growth Factor Receptor 2 (HER2) Negative Unresectable Locally Advanced or Metastatic G/GEJ Adenocarcinoma
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 294
- 试验地点
- 1
- 主要终点
- Incidence and severity of adverse events(AE)
研究概览
简要总结
Phase Ib/II clinical study of AK129 combined with chemotherapy with or without cadonilimab in first-line treatment of advanced HER2 negative gastric cancer or gastroesophageal junction adenocarcinoma
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The subject must sign the written informed consent form(ICF) voluntarily.
- •Aged ≥ 18 to ≤ 75 years,male and female at the time of signing the ICF.
- •Histologically confirmed adenocarcinoma of the gastric or gastroesophageal junction (GEJ).
- •Inoperable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma.
- •Participants had not previously received systemic therapy for locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma.
- •According to RECIST v1.1 criteria, subjects had at least one measurable tumor target.
排除标准
- •Subjects with known HER2 positive gastric or gastroesophageal junction adenocarcinoma.
- •Histopathological examination confirmed other pathological types.
- •Had received palliative local therapy for non-target lesions within 2 weeks before the first administration.
- •Past treatment with immune checkpoint inhibitors,immune checkpoint agonists,immune cell therapy and any treatment targeting the immune mechanism of tumor action.
- •History of gastrointestinal perforation and fistula within 6 months before the first dose.
- •Active or previously documented inflammatory bowel disease,inability to swallow, malabsorption syndrome.
- •Active malignancy within the last 3 years.
- •Active or untreated brain metastases, meningeal metastases, spinal cord compression, or pia meningeal disease are known to exist.
- •The presence of clinical symptoms of pleural effusion, pericardial effusion, or abdominal effusion, or the need for frequent drainage.
- •There was an active autoimmune disease that required systemic treatment within 2 years prior to the start of the study.
结局指标
主要结局
Incidence and severity of adverse events(AE)
时间窗: Up to approximately 2 years
Incidence and severity of AEs is aim to evaluate the safety of AK129 combined with chemotherapy with or without cadonilimab
Incidence of serious adverse events(SAE) and suspected unexpected serious adverse reactions(SUSAR)
时间窗: Up to approximately 2 years
Incidence of SAE and SUSAR is aim to evaluate the safety of AK129 combined with chemotherapy with or without cadonilimab
Incidence of dose-limiting toxicity(DLT)
时间窗: Up to approximately 2 years
The purpose of DLT is to find the Phase II recommended dose(RP2D) or Maximum Tolerated Dose(MTD)
Clinically significant changes in safety/laboratory evaluation parameters and AEs that led to treatment termination or suspension
时间窗: Up to approximately 2 years
Clinically significant changes in safety/laboratory evaluation parameters and AEs that led to treatment termination or suspension is aim to evaluate the safety of AK129 combined with chemotherapy with or without cadonilimab
Objective Solution Rate (ORR) based on RECIST v1.1
时间窗: Up to approximately 2 years
The purpose of ORR is aim to evaluate the antitumor effect,and ORR is proportion of subjects with complete response(CR) or partial response(PR), based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1.
次要结局
- Disease control rate(DCR)(Up to approximately 2 years)
- duration of response(DoR)(Up to approximately 2 years)
- time to response(TTR)(Up to approximately 2 years)
- progression-free survival(PFS)(Up to approximately 2 years)
- overall survival(OS)(Up to approximately 2 years)
- Serum AK129, cadonilimab concentration, blood concentration-time curve and derived PK argument(Up to approximately 2 years)
- Number and percentage of subjects with anti-drug antibodies (ADA) for AK129 and cadonilimab(Up to approximately 2 years)