A Multicentre, Phase Ib/II Clinical Study of AK109 and AK104 With or Without Chemotherapy in Second-line Treatment of Advanced Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 138
- 试验地点
- 1
- 主要终点
- Objective response rate (ORR)
研究概览
简要总结
This is a multicentre, Phase Ib/II Clinical Study of AK109 and AK104 With or Without Chemotherapy in Second-line Treatment of Advanced Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma .
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Written and signed informed consent
- •Age ≥ 18 years but ≤ 75 years
- •ECOG of 0 or
- •Estimated life expectancy of ≥3 months.
- •Histologically or cytologically documented advanced unresectable or metastatic gastric adenocarcinoma or gastroesophageal Junction (GEJ) adenocarcinoma.
- •At least one measurable lesion per RECIST v1.
- •Gastric adenocarcinoma or gastroesophageal junction (GEJ) adenocarcinoma with failure of first-line treatment with anti-PD-1/L1 and chemotherapy
- •Adequate organ function.
- •Have agreed to take effective contraception from the date of signing the informed consent form until 120 days after the last administration.
排除标准
- •Other invasive malignancies within 3 years, except for locally treatable (manifested as cured) malignancies, such as basal or skin squamous cell carcinoma, superficial bladder cancer, cervical or breast carcinoma in situ.
- •Any previous systemic therapy targeting VEGF or anti-VEGFR signaling pathways.
- •In addition to PD1 or PD-L1,Prior exposure to anti-CTLA-4 antibody, or any other antibody or drug therapy for T cell co-stimulatory or checkpoint pathways, such as ICOS or agonists (e.g. CD40, CD137, GITR and OX40 etc).
- •Known history of primary immunodeficiency virus infection.
- •Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
- •Known history of interstitial lung disease.
- •Known history of active tuberculosis (TB).
- •Central nervous system (CNS) metastasis, meningeal metastasis, spinal cord compression, or leptomeningeal disease.
- •Patients with untreated chronic hepatitis B or HBV DNA exceeding 500IU/mL or active hepatitis C should be excluded. Patients with HCV antibody positive are eligible to participate in the study if the results of HCV RNA test show negative.
- •Known history of testing positive for human immunodeficiency virus (HIV).
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
- •Subjects with active, known or suspected autoimmune disease, or a medical history of autoimmune disease, with the exceptions of the following: vitiligo, alopecia, Grave disease, psoriasis or eczema not requiring systemic treatment within the last 2 years, hypothyroidism (caused by autoimmune thyroiditis) only requiring steady doses of hormone replacement therapy and type I diabetes only requiring steady doses of insulin replacement therapy, or completely relieved childhood asthma that requires no intervention in adulthood, or primary diseases that will not relapse unless triggered by external factors.
- •Pregnant or lactating women.
研究组 & 干预措施
AK109 combined with chemotherapy
AK109 combined with paclitaxel, iv, every 3 weeks
干预措施: AK109 (Biological)
AK109 combined with chemotherapy
AK109 combined with paclitaxel, iv, every 3 weeks
干预措施: paclitaxel (Drug)
AK104 and AK109 combined with chemotherapy
AK104 combined with AK109 and paclitaxel, iv, every 3 weeks
干预措施: AK109 (Biological)
AK104 and AK109 combined with chemotherapy
AK104 combined with AK109 and paclitaxel, iv, every 3 weeks
干预措施: paclitaxel (Drug)
AK104 and AK109 combined with chemotherapy
AK104 combined with AK109 and paclitaxel, iv, every 3 weeks
干预措施: AK104 (Biological)
结局指标
主要结局
Objective response rate (ORR)
时间窗: up to 2 years
The ORR is defined as the proportion of subjects with CR or PR, based on RECIST Version 1.1.
Adverse events (AEs)
时间窗: up to 2 years
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Number of subjects experiencing dose-limiting toxicities (DLTs)
时间窗: During the first 4 weeks
DLTs will be assessed during the first 28 days of treatment and are defined as toxicities that meet pre-defined severity criteria, and assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications .
次要结局
- Duration of response (DoR)(Up to 2 years)
- Number of subjects who develop detectable anti-drug antibodies (ADAs)(From first dose of AK109 and AK104 through 90 days after last dose of AK109 and AK104)
- Observed pharmacokinetics (PK) exposure of AK109 and AK104(From first dose of AK109 and AK104 through 90 days after last dose of AK109 and AK104)
- Progression-free survival (PFS)(Up to 2 years)
- Disease control rate (DCR)(Up to 2 years)
- Overall survival (OS)(up to 2 years)