An Open-Label, Multicenter, Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of KJ015 Injection (Subcutaneous Injection) in Patients With HER2-Expressing Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 66
- 试验地点
- 1
- 主要终点
- Dose Escalation Part: Adverse Event collection and assessment
研究概览
简要总结
This is an open-label, multicenter, Phase 1 study to evaluate the safety, tolerability, PK, and preliminary efficacy of KJ015 administered subcutaneously in participants with HER2-expressing solid tumors.
详细描述
This is an open-label, multicenter, Phase 1 study to evaluate the safety, tolerability, PK, and preliminary efficacy of KJ015 administered subcutaneously in participants with HER2-expressing solid tumors. The study will be conducted in 2 parts: the first part is the dose escalation part, and the second part is the Backfill part (as determined by the Sponsor). The dose escalation part will evaluate the safety and tolerability of KJ015 in participants with HER2-expressing locally advanced or metastatic solid tumors who have no standard therapy, are ineligible for surgical resection, or are not suitable for standard therapy or other approved therapies but have an inadequate clinical response. The Backfill part will further characterize the preliminary efficacy and safety of KJ015 in selected participants with solid tumors (including but not limited to G/GEJ, BC, CRC, BDC, HNSCC, NSCLC, etc.) at a minimum of two safe and tolerable dose levels, explore the relationship between the expression levels of HER2 protein and its mRNA and efficacy, as well as the HER 2 protein expression levels, transcription levels, and the correlation with efficacy in antitumor activity after KJ015 treatment.
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
- •Aged ≥ 18 years (at time of free and informed consent).
- •Participants must have radiographically confirmed progressive disease (PD) during the last treatment prior to the first dose of enrollment.
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) Dose Escalation Part: ECOG performance status 0 to 1;Backfill Part: ECOG performance status0 to
- •Participants must be have HER 2 positive or HER 2 expressing tumors determined by a certified local or central clinical laboratory or hospital
- •Organ function must meet the following criteria:
- •i.Hemoglobin (Hb) ≥ 9.0 g/dL ii.Absolute neutrophil count (ANC) ≥ 1.0 × 109/L iii.Platelet count (PLT) ≥ 80 × 109/L v.Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN if no liver lesions (primary or metastatic); ALT and AST ≤ 5 × ULN if liver lesions are present vi.Creatinine clearance ≥ 30 mL/min vii.Activated partial thromboplastin time (APTT) and international normalized ratio (INR) ≤ 1.5 × ULN viii. Serum albumin ≥ 25 g/L (2.5 g/dL).
- •Expected survival ≥ 3 months.
- •Participants must be capable of and willing to comply with the visit and procedure requirements outlined in the protocol.
排除标准
- •Concurrent participation in another clinical study.
- •Received radiotherapy within 2 weeks prior to the first dose.
- •Underwent major surgery (excluding diagnostic surgery) within 4 weeks prior to the first dose or plan to undergo major surgery during the study. Underwent interventional or ablation surgery aimed at treating the tumor within 2 weeks before the first dose.
- •Prior allogeneic bone marrow transplant or prior solid organ transplant.
- •Received systemic corticosteroids or other immunosuppressive treatments within 2 weeks prior to the first dose.
- •Received an anthracycline cumulative dose of doxorubicin exceeding 500 mg/m2 or an equivalent dose of other anthracyclines prior to the first dose.
- •History of leptomeningeal carcinomatosis or carcinomatous meningitis.
- •Brain metastasis or spinal cord compression.
- •Uncontrolled or clinically significant cardiovascular or cerebrovascular disease.
- •History of a serious allergic reaction to the investigational product, an inactive ingredient in the investigational product, or other monoclonal antibody.
- •Women who are pregnant or breastfeeding as confirmed by pregnancy testing within 3 days prior to first dose.
研究组 & 干预措施
KJ015 Injection (Subcutaneous Injection)
KJ015 is administered via subcutaneous injection.
干预措施: KJ015 Injection (Subcutaneous Injection) (Drug)
结局指标
主要结局
Dose Escalation Part: Adverse Event collection and assessment
时间窗: at least 21 days or up to 24 weeks
Adverse Event collection and assessment will be done for all potentially treated subjects to assess the safety, tolerability, and determine the DLTs, maximum tolerated dose (MTD).
Dose Escalation Part: Backfill part recommended extension dose (RED)
时间窗: at least 21 days or up to 24 weeks
Backfill recommended extension dose
Backfill Part: Adverse Event
时间窗: at least 21 days or up to 24 weeks
Adverse Event collection and assessment will be done for all potentially treated subjects to assess the safety, tolerability.
次要结局
- Immunogenicity(day 1, day 15, every 3 weeks)
- Objective Response Rate (ORR)(at least 12 weeks)
- Disease Control Rate (DCR)(at least 12 weeks)
- Progression-Free Survival（PFS）(at least 12 weeks)
- Overall Survival (OS)(at least 12 weeks)
- Maximum Observed Plasma Concentration (Cmax)(Pre-dose, 2-24, 48, 72, 96, 144-480 hours post-dose)
- Terminal Half-life (t½)(Pre-dose, 2-24, 48, 72, 96, 144-480 hours post-dose)
- Area under the serum concentration versustime curve (AUC)(Pre-dose, 2-24, 48, 72, 96, 144-480 hours post-dose)
- Apparent Volume of Distribution (Vz)(Pre-dose, 2-24, 48, 72, 96, 144-480 hours post-dose)
- Clearance(CL)(Pre-dose, 2-24, 48, 72, 96, 144-480 hours post-dose)