A Phase 1 Dose Escalation Trial to Determine the Safety, Tolerance, Maximum Tolerated Dose, and Preliminary Antineoplastic Activity of the IKS04 Regimen Targeting CA242
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 120
- 试验地点
- 4
- 主要终点
- Recommended Phase 2 Dose (Part I)
研究概览
简要总结
This study will evaluate the safety, tolerability, anti-tumor activity, immunogenicity, pharmacokinetics and pharmacodynamics of the IKS04 Regimen and identify a recommended phase 2 dose (RP2D) or recommended dose for further evaluation in expansion (RDE). The regimen includes Isumab04 (unconjugated antibody) followed by the IKS04 antibody-drug conjugate, both directed against the CA242 (CanAg) tumor-associated antigen and administered intravenously (IV) in patients with advanced solid cancers.
详细描述
The study will consist of 2 parts: dose-escalation (Part I) and dose-expansion (Part II). The dose-escalation part (Part I) will evaluate the safety and tolerability of increasing dose levels of the IKS04 Regimen and to establish a RP2D and/or a RDE; and the dose-expansion portion (Part II) of the study will further characterize the safety, pharmacokinetics/pharmacodynamics, and efficacy of the IKS04 Regimen at the RP2D or RDE. Participants may continue on study until disease progression, unacceptable toxicity, or other withdrawal criteria is met.
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
- 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
- •Advanced or metastatic CRC, BTCs, GEA, and PDAC that is histologically or cytologically confirmed
- •Disease that has progressed despite prior treatment, for which additional effective therapy is not available, not tolerable, is contraindicated, or the participant refuses standard therapy.
- •Platelets ≥ 100,000 /mcL
- •Hemoglobin ≥ 9.0 g/dL., no transfusions with RBCs are allowed within 2 weeks prior to first trial drug administration
- •ANC ≥ 1500/mcL
- •Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 3 x institutional upper limit of normal (ULN) ≤ 5 x ULN if liver metastases present
- •Total bilirubin ≤ 1.5 x ULN, unless participant has Gilbert's Syndrome
- •Albumin > 2.5 g/dL
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
- •Fresh biopsy tissue or formalin-fixed paraffin-embedded (FFPE) tumor tissue block or slides available for retrospective assessment of CA242 positivity in a central laboratory.
- •Measurable and non-measurable disease
- •Fresh biopsy tissue or FFPE tumor tissue block or slides for assessment of CA242 positivity in a central laboratory prior to administration of first dose of study drug.
- •Measurable disease only
排除标准
- •Participants with a significant pulmonary disease or condition, including:
- •Significant symptomatic chronic obstructive pulmonary disease (COPD), as assessed by the Investigator.
- •History or any current evidence on imaging studies of interstitial lung disease (ILD), pulmonary fibrosis.
- •History of pulmonary inflammatory disease, pneumonitis, acute respiratory distress syndrome (ARDS).
- •History of pneumonia within 3 months prior to the first trial drug administration.
- •Participants who have received previous treatment with any CA242 directed ADC or any ADC containing a PBD payload for their current tumor indication.
- •Participant may not have received more than 5 prior lines of systemic therapy.
- •Received treatment with a strong cytochrome P450 (CYP) 3A4 inhibitor within 7 days or 5 half-lives (whichever is longer) prior to the first trial drug administration
- •Central nervous system metastatic disease unless treated prior to first dose of trial drug.
- •Active second malignancy or history of another malignancy within the last 2 years with specific exceptions as per protocol
- •Active, known or suspected autoimmune disease, or a documented history of autoimmune disease or syndrome requiring systemic steroids or other immunosuppressive medications, such as:
- •Myocarditis, pneumonitis, glomerulonephritis.
- •Autoimmune hepatitis, inflammatory bowel disease (IBD)
- •Sjogren's syndrome
- •Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE)
- •Myasthenia gravis
- •Guillain-Barré Syndrome
- •Multiple sclerosis
- •Granulomatosis with polyangiitis (Wegner's granulomatosis)
- •Vasculitis
结局指标
主要结局
Recommended Phase 2 Dose (Part I)
时间窗: Up to 24 months
Based on tolerability, preliminary anti-tumor activity, and pharmacokinetics
Objective Response Rate (Part II)
时间窗: Up to 24 months
Anti-tumor activity will be assessed by RECIST 1.1
次要结局
- Objective Response Rate(Up to 24 months)
- Maximum Concentration (Cmax) (Part I and II)(Up to 48 months)
- Area under the plasma concentration versus time curve (AUC) (Part I and II)(48 months)
- Half-life (T1/2) (Part I and II)(48 months)
- Evaluation of Immunogenicity of IKS04 Regimen (Part I and II)(Up to 48 months)