A Prospective, Open-label, Dose Escalation (Part A) and Cohort Expansion (Part B) Phase 1 Study to Investigate the Safety, Tolerability, and Immunogenicity and to Determine Maximum Tolerated Dose and Recommended Phase 2 Dose of GC1118 (Recombinant Human Anti-EGFR Antibody) in Patients With Advanced Solid Cancers
试验速览
- 阶段
- 1 期
- 入组人数
- 72
- 试验地点
- 2
- 主要终点
- Occurrence of Dose Limiting Toxicity (DLT)
研究概览
简要总结
The purpose of this study is to determine the maximum tolerated dose(MTD)/Recommended Phase 2 Dose(RP2D) and to evaluate the safety and tolerability of GC1118 when given by intravenous (IV) infusion to patients with stage IV solid tumors.
The study will also evaluate pharmacokinetics, immunogenicity and antitumor effect of GC1118 and explore prognostic biomarkers and pharmacodynamic biomarkers.
详细描述
An open-label, single-arm, multi-center, phase 1, dose-escalation study will be conducted to define the MTD/RP2D, safety, PK, immunogenicity and antitumor activity of GC1118 in patients with refractory disease for whom no standard therapy is available.
This study is in three parts: a dose escalation segment (Part A), a cohort expansion (Part B) and biweekly administration(Part C). In part A, a dose escalation schema will be applied in dose level cohorts. GC1118 will be administered weekly on Study Day 1, 8, 15, and 22 of each 28-day cycle by IV infusion. Dose escalation may occur as described in the study protocol. Once the MTD has been established during Part A, the MTD cohort will be expanded in part B. And GC1118 will be administered biweekly on Study Day 1, 15 each 28-day cycle by IV infusion in part C.
Study assessments will include AE monitoring including physical examination, vital signs and clinical laboratory tests, ECG monitoring, PK analysis of serum GC1118, an assessment of potential anti-GC1118 antibody response and an exploration of potential prognostic and pharmacodynamic biomarkers.
Tumor response assessments using Study Day 36 CT/MRI scans will be performed approximately five weeks after the first GC1118 dose for each patient (Part A only). Patients with evidence of disease regression (partial or complete response or stable disease by RECIST criteria) will be allowed to continue therapy at the same dose. Subsequent cycles will consist of administration of GC1118 on Day 1, 8, 15, and 22 of each 28-day cycle with tumor evaluation every other cycle (approximately every 8 weeks) in part A,B and Day 1, 15 of each 28-day cycle with tumor evaluation every other cycle (approximately every 8 weeks) in part C.
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
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willing and able to sign a written informed consent
- •Nineteen (19) years of age or older
- •For Part A and Part C, all stage IV advanced solid cancers For Part B, stage IV of gastric cancer, colorectal cancer or other cancer
- •Cohort1: Metastatic CRC (K-RAS wild), No prior treatment with EGFR antibody therapeutics
- •Cohort2: Metastatic CRC (K-RAS wild), Progressed over EGFR antibody therapeutics
- •Cohort3: Advanced gastric or gastroesophageal junction cancer(EGFR++ or +++ /HER2-)
- •For Part A and Part C, refractory solid tumors to conventional therapy (Progressive disease during or after previous conventional therapy)
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of less than or equal to 1
- •Life expectancy of greater than or equal to 3 months
- •Availability of a new tumor biopsy or able to obtain unstained slides of tumor within 3 years
- •For Part B, at least one measurable tumor mass by RECIST v1.1
- •Acceptable laboratory parameters
- •If all AEs caused by the previous anti-cancer therapies including surgery, chemotherapy and radiation therapy have recovered to CTCAE grade 1 or below (except alopecia)
排除标准
- •Has had any major surgery or any therapy within the last 4 weeks and/or not recovered from prior therapy
- •Has had chemotherapy, surgery or radiotherapy within the previous 4 weeks
- •Confirmed brain metastases
- •Chronic Hepatitis C or known HIV positive patients
- •Liver Cirrhosis or active hepatitis B virus (HBV) carrier
- •Clinically significant interstitial pulmonary disease
- •Has received prior treatment with cetuximab or anti-EGFR antibody therapy is not permitted in Part B(however, allowed in Part A and Part C)
- •Clinically significant cardiac disease or impaired cardiac function
- •Acute or subacute intestinal obstruction or Inflammatory bowel disease
- •Has had immunotherapy, chemotherapy or hormonal therapy prohibited as per study protocol
- •Has participated in any study using an investigational drug during the previous 4 weeks
- •Known hypersensitivity to the study drug
- •History of second primary malignancy within 3 years prior to starting study treatment (excluding early gastric cancer, thyroid cancer, cervical cancer or skin cancer)
- •Severe renal impairment
- •Severe hepatic impairment
- •Current active infection
- •Known KRAS-mutation for Part A and Part C, Known KRAS-mutation for Part B or BRAF matant
- •Medical or psychiatric illness that, in the opinion of the investigator, may affect compliance with scheduled visits
- •Pregnant (potentially fertile patients) or lactating women
- •Patients refuse to use acceptable forms of contraceptions from the time of consent through six months after the study drug administration
结局指标
主要结局
Occurrence of Dose Limiting Toxicity (DLT)
时间窗: Approx. 6 months
Frequency of Adverse Events
时间窗: Approx. 6 months
Changes in safety parameters, laboratory values, vital signs and physical examinations
时间窗: Approx. 6 months
Vital sign assessment will include systolic and diastolic blood pressure, heart rate, respiration rate and temperature. Laboratory values will include hematology and clinical chemistry.
次要结局
- Overall Response Rate (ORR) as per Response Evaluation Criteria in Solid Tumors(RECIST) v1.1(Approx. 6 months)
- Disease Control Rate (DCR) as per Response Evaluation Criteria in Solid Tumors(RECIST) v1.1(Approx. 6 months)
- Progression-Free Survival (PFS) as per Response Evaluation Criteria in Solid Tumors(RECIST) v1.1 (Part B)(Approx. 6 months)
- Time versus plasma concentration profiles and basic PK parameters of GC1118(Approx. 6 months)
- Presence of Human Anti Drug Antibody(Approx. 6 months)