A Phase 1, Uncontrolled, Open-label, Non-randomized, Dose-escalation Study of KK2260 in Patients With Advanced or Metastatic Solid Tumors, Followed by an Uncontrolled, Non-randomized Study and an Uncontrolled, Randomized Study in Patients With Esophageal Squamous Cell Carcinoma or Head and Neck Squamous Cell Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 189
- 试验地点
- 14
- 主要终点
- Dose-limiting toxicity (Only in Part 1a)
研究概览
简要总结
This is the first in human study of KK2260. In Part 1a, the maximum tolerated dose (MTD) will be determined while evaluating the safety and tolerability of KK2260 in patients with advanced or metastatic solid tumors (any cancer type). In Part 1b and Part 2, at least two dosing regimens and two dosing regimens by cancer type, respectively, will be selected, and the safety, tolerability, and efficacy of each regimen will be evaluated.
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
- 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
- •<Common Inclusion Criteria for Part 1a, Part 1b, and Part 2
- •Patients who have given informed written consent.
- •Male or female subjects ≥18 years of age, at time of signing informed consent.
- •Subjects who are refractory to standard treatment, intolerant of standard treatment, for whom standard treatment does not exist, or who have refused standard treatment.
- •Patients with measurable disease according to RECIST version 1.1
- •Patients who have had the certaion periods between the date of completion of prior therapy and the date of enrollment
- •Subjects who agree to have a tumor biopsy as part of the baseline examination. Patients who have difficulty in performing a tumour biopsy and have agreed to submit a previously collected stored specimen.
- •Patients with an ECOG PS of 0 or 1 at baseline.
- •Patients with haematopoietic, hepatic, renal, cardiac and respiratory functions that meet certain criteria in a baseline test.
- •<Additional Inclusion Criteria for Part 1a
- •1) Patients with pathologically diagnosed advanced or metastatic solid tumors.
- •<Additional Inclusion Criteria for Part 1b
- •Patients with pathologically diagnosed with advanced or metastatic esophageal cancer, or advanced or metastatic head and neck cancer whose primary site of origin is the oral cavity, oropharynx, hypopharynx, larynx, nasal cavity, or paranasal sinuses.
- •Patients with pathologically diagnosed squamous cell carcinoma.
- •Patients who agree to undergo tumor biopsy after administration.
- •<Additional Inclusion Criteria for Part 2a
- •Patients with pathologically diagnosed with advanced or metastatic esophageal cancer.
- •Patients with pathologically diagnosed squamous cell carcinoma.
- •Patients who agree to undergo tumor biopsy after administration.
- •<Additional Inclusion Criteria for Part 2b
- •Patients with advanced or metastatic head and neck cancer whose primary site of origin is the oral cavity, oropharynx, hypopharynx, larynx, nasal cavity, or paranasal sinuses.
- •Patients with pathologically diagnosed squamous cell carcinoma.
- •Patients who agree to undergo tumor biopsy after administration.
排除标准
- •\ 1. Patients with central or brain pia mater metastases that are untreated and symptomatic or that require treatment.
- •2. Patients with concurrent multiple or synchronous cancers, or with iatrogenic multiple or synchronous cancers with a disease-free interval of 5 years or less.
- •3. Patients receiving continuous systemic administration of steroids or other immunosuppressive drugs.
- •4. Patients who have had a Grade 3 or higher allergic reaction to an antibody agent or an additive of the study drug.
- •5. Patients who have not recovered to Grade 1 or below from adverse events caused by previously administered anticancer therapy.
- •6. Patients with active interstitial lung disease or a history of active interstitial lung disease.
- •7. Patients with infectious diseases requiring systemic treatment.
- •8. Patients with a fever of 38.0°C or higher at the time of registration.
- •9. Patients who test positive for Hepatitis B virus antigen or antibody, Hepatitis C virus antibody, or HIV antibody in a baseline test.
研究组 & 干预措施
KK2260 (Dosing regimen 2)
干预措施: KK2260 (Drug)
KK2260 (Dosing regimen 1)
干预措施: KK2260 (Drug)
结局指标
主要结局
Dose-limiting toxicity (Only in Part 1a)
时间窗: During the first cycle (1 Cycle = 28 days)
Adverse Events
时间窗: Through study completion, an average of 1 year
Changes in Laboratory Testing Values (Red blood cell count)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Hemoglobin concentration)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Hematocrit)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Reticulocyte)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Mean corpuscular volume)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Mean corpuscular hemoglobin)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Mean corpuscular hemoglobin concentration)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (White blood cell count)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Differential white blood cells (basophils, eosinophils, lymphocytes, monocytes, neutrophils))
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Platelet count)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Total protein)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Albumin)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Alkaline phosphatase)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Alanine aminotransferase/Aspartate aminotransferase)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Total bilirubin/Direct bilirubin)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Blood urea nitrogen)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Calcium/Corrected Calcium)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Chloride)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Potassium)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Sodium)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Magnesium)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Serum iron)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Ferritin)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Total iron binding capacity)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Unsaturated iron binding capacity)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Serum creatinine)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Lactate dehydrogenase)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Blood glucose)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Uric acid)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Lipase)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Amylase)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (C-reactive protein)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Gamma-glutamyl transpeptidase)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Triglycerides)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Cholesterol)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Creatine phosphokinase)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Coagulation test)
时间窗: Every week through study completion, an average of 1 year
Prothrombin time international normalized ratio and Activated partial thromboplastin time
Changes in Laboratory Testing Values (Hepatitis B virus DNA, if needed)
时间窗: Every 2 cycle through study completion, an average of 1 year (1 Cycle = 28 days)
Changes in Body temperature (degree Celsius)
时间窗: Every week through study completion, an average of 1 year
Changes in Systolic and Diastolic Blood Pressure (mmHg)
时间窗: Every week through study completion, an average of 1 year
Changes in SpO2 (%)
时间窗: Every week through study completion, an average of 1 year
Changes in Electrocardiogram parameters (Heart rate, PR interval, QRS interval, QT interval, and QTc intervals)
时间窗: Every week through study completion, an average of 1 year
The resting Heart rate, PR interval, QRS interval, QT interval, and QTc intervals will be recorded. Any abnormalities in ECG will be specified and documented as clinically significant or not clinically significant.
Changes in Eastern Cooperative Oncology Group Performance Status (ECOG PS) (The score should be 0 to 4, and the lower is the better.)
时间窗: Every week through study completion, an average of 1 year
Changes in Laboratory Testing Values (Creatinine clearance (Cockcroft-Gault formula))
时间窗: Every week through study completion, an average of 1 year
次要结局
- Serum concentration levels of KK2260(Pre-dose and post-dose at multiple timepoints for each cycle during the intervention (each cycle is 28 days))
- Maximum Plasma Concentration (Cmax)(Pre-dose and post-dose at multiple timepoints for each cycle during the intervention (each cycle is 28 days))
- Area Under the blood concentration-time Curve (AUC)(Pre-dose and post-dose at multiple timepoints for each cycle during the intervention (each cycle is 28 days))
- Anti-drug antibody(Pre-dose and post-dose at multiple timepoints for each cycle during the intervention (each cycle is 28 days))
- Overall Response Rate (in Part 1b/2)(During the treatment and every 12 weeks after study treatment completion (approximately up to 1 year))
- Disease Control Rate (in Part 1b/2)(During the treatment and every 12 weeks after study treatment completion (approximately up to 1 year))
- Duration of Response (in Part 1b/2)(During the treatment and every 12 weeks after study treatment completion (approximately up to 1 year))
- Progression-Free Survival (in Part 1b/2)(During the treatment and every 12 weeks after study treatment completion (approximately up to 1 year))
- Overall Survival (in Part 1b/2)(During the treatment and every 12 weeks after study treatment completion (approximately up to 1 year))
- Time to Response (in Part 1b/2)(During the treatment and every 12 weeks after study treatment completion (approximately up to 1 year))