A Phase 1 Study of TJ033721 in Subjects With Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 330
- 试验地点
- 21
- 主要终点
- Maximum tolerated or administered dose (MTD, MAD)
研究概览
简要总结
This is an open label, multi-center, multiple dose Phase 1 study to evaluate the safety, tolerability, MTD PK, and PD of TJ033721 (givastomig) in subjects with advanced or metastatic solid tumors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Care Provider)
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
- •Part 1 - Monotherapy Subjects with advanced or metastatic solid tumor in subjects whose disease has progressed despite standard therapy, or who has no further standard therapy, or who is unsuitable for available standard treatment options.
- •Part 2 - Combination Therapy Subjects with treatment naïve locally advanced, unresectable or metastatic gastric, GEJ, esophageal adenocarcinoma;
- •Part 3: Combination Therapy Subjects with unresectable, locally advanced or metastatic histologically confirmed pancreatic adenocarcinoma;
- •Part 4: Combination Therapy Subjects with unresectable, locally advanced or metastatic histologically confirmed biliary tract cancer.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 with adequate organ function
- •Have known PD-L1 status with prior testing by immunohistochemistry and a corresponding combined positive score (CPS)
- •For dose expansion and Part 2, Part 3, Part 4 Combination subjects:
- •Must have CLDN18.2-positive tumor expression
排除标准
- •Prior exposure to CLDN18.2 -targeted therapy
- •Prior exposure to 4-1BB agonists
- •Second malignancy within the last 3 years with the exception of cutaneous squamous cell carcinoma or cutaneous basal cell carcinoma or cervical carcinoma in situ
- •Known active or chronic Hepatitis B or Hepatitis C, other hepatitides
- •Unstable/active ulcer or digestive tract bleeding within 6 weeks
- •Active autoimmune disease requiring systemic treatment within the past 2 years
- •Active interstitial lung disease (ILD) or pneumonitis or a history of ILD or pneumonitis requiring treatment
- •Known active CNS metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment;
- •New York Heart Association (NYHA) Class 3 or 4 congestive heart failure, severe/unstable angina, myocardial infarction (MI), symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack (TIA), arterial embolism, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass grafting (CABG) in the previous 6 months
- •Diagnosis of immunodeficiency such as known active HIV
- •Any active infection requiring parenteral treatment
- •For Part 2, 3, 4 Combination subjects:
- •Prior treatment with anti-PD-1 or PD-L1 agent
研究组 & 干预措施
TJ033721 (givastomig)
Dose Escalation: TJ033721 will be administered at up to 8 dose levels (0.1, 0.3, 1, 3, 5, 8, 12 and 15 mg/kg) bi weekly (Q2W) and 1 dose level (18 mg/kg) every 3 weeks (Q3W)
During dose expansion, TJ033721 will be administered Q2W, starting at the RP2D or MTD in dose escalation.
干预措施: TJ033721 (givastomig) (Drug)
TJ033721 (givastomig) in combination with nivolumab and chemotherapy
TJ033721 will be administered in combination with nivolumab and chemotherapy
干预措施: TJ033721 (givastomig) , nivolumab, chemotherapy (Drug)
TJ033721 (givastomig) in combination chemotherapy
TJ033721 (givastomig) will be administered in combination chemotherapy
干预措施: TJ033721 (givastomig), chemotherapy (Drug)
TJ033721 (givastomig) in combination with durvalumab and chemotherapy
TJ033721 (givastomig) will be administered in combination with durvalumab and chemotherapy
干预措施: TJ033721 (givastomig), durvalumab, chemotherapy (Drug)
结局指标
主要结局
Maximum tolerated or administered dose (MTD, MAD)
时间窗: 28 Days
Based on DLT definitions
Incidence and severity of AEs
时间窗: Up to 100 days post last dose
The CTCAE criteria will be used to assess adverse events on this trial.
Dose-limiting toxicities (DLTs)
时间窗: 28 days
次要结局
- Pharmacokinetic (PK) Parameters: Cmax(up to 100 days post last dose)
- Pharmacokinetic Parameters: T1/2(up to 100 days post last dose)
- Pharmacokinetic (PK) Parameters: AUC∞(Up to 100 days post last dose)
- Pharmacokinetic (PK) Parameters: AUCt(up to 100 days post last dose)
- Pharmacokinetic Parameters: Tmax(up to 100 days post last dose)