A First-in-Human, Multicenter, Open-Label, Phase 1/2a Study to Evaluate the Safety, Efficacy and Pharmacokinetics of CKD-703 in Advanced c-Met Expressing Solid Tumors, and in MET Amplified and c-Met Overexpressing Non-Small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 140
- 试验地点
- 1
- 主要终点
- Part 1: Number of patients with dose limiting toxicity (DLT)
研究概览
简要总结
This is a Phase 1/2a open-label multicenter study to evaluate the safety, efficacy, and pharmacokinetics of CKD-703 in Advanced c-Met Expressing Solid Tumors, and in MET-Amplified and c-Met Overexpressing Non-Small Cell Lung Cancer.
CKD-703 is composed of a c-Met-targeting monoclonal antibody (mAb) coupled to a cytotoxic payload consisting of the anti-microtubule drug monomethyl auristatin E (MMAE); thus, CKD-703 is a novel ADC offering a highly targeted approach with potential improvement of efficacy while reducing off-target effects for patients with NSCLC and other cancers.
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
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females ≥ 19-year-old
- •Part 1 : Solid tumors including NSCLC for which standard therapy has failed or was not tolerated, and no other effective therapy exists
- •Part 2 : Histologically or cytologically documented c-Met overexpressing nonsquamous NSCLC having failed at least 1 line of SoC therapy (platinum-based chemotherapy and/or immune checkpoint inhibitor).
- •Part 3 : Histologically or cytologically documented c-Met expressing solid tumors for which standard therapy has failed or was not tolerated.
- •In all parts of the study, subjects with NSCLC with documented actionable genetic alterations must have failed at least 1 line of country-level approved targeted therapies
- •Life expectancy ≥ 12 weeks as judged by the Investigator
- •Documented progressive and measurable disease as defined by RECIST 1.1
- •ECOG Performance Status 0 or 1
排除标准
- •Subject has received radiation therapy to the lung < 6 months prior to the first dose of study drug
- •Prior radiotherapy to ≥ 25% of bone marrow
- •Anticancer systemic therapy such as immunotherapy, biologic, cytotoxic chemotherapy, or any investigational therapy (including cell therapy or gene therapy) within a period of 28 days prior to the first dose of study drug. Any anticancer therapy small molecule (eg. kinase inhibitor) or herbal therapy within 14 days prior to the first dose of study drug
- •Prior c-Met-targeted antibody therapy or any MMAE-containing ADC (prior c-Met targeting small molecules are allowed)
- •Use of strong P-gp and/or CYP3A4/5 inducers within 21 days prior or strong P-gp and/or CYP3A4/5 inhibitors within 14 days prior to the first dose of study drug
- •Use of sensitive CYP3A4/5 substrate within 3 days or 5 times half-life prior to the first dose of study drug.
- •Evidence of pulmonary fibrosis on screening imaging assessment or any history of pneumonitis that required treatment with systemic steroids within 12 months of the planned first dose of the study drug
- •History of drug induced interstitial lung disease
- •Prior or active ocular or corneal disease based on ophthalmic evaluation (slit lamp and visual acuity)
- •Prior Grade 3 neuropathy or chronic Grade 2 neuropathy
研究组 & 干预措施
Part 1
Participants with advanced solid tumors will receive escalating dose of CKD-703
干预措施: CKD-703 (Drug)
Part 2
Participants with nsqNSCLC will receive CKD-703
干预措施: CKD-703 (Drug)
Part 3
Participants with advanced solid tumors will receive CKD-703
干预措施: CKD-703 (Drug)
结局指标
主要结局
Part 1: Number of patients with dose limiting toxicity (DLT)
时间窗: first 21-day period of therapy
Collect all adverse events at each visit
Part 2 and Part 3: Object Response Rate (ORR)
时间窗: Up to 24 months
ORR defined as the proportion of subjects with a best Investigator-assessed confirmed objective response of CR or PR according to RECIST 1.1
次要结局
- All parts : Treatment-Emergent Adverse Events (TEAE)(Up to 24 months)
- All parts : Immunogenicity (ADA)(Up to 24 months)
- All parts : Immunogenicity (NAb)(Up to 24 months)
- Part 1 and Part 2 : Pharmacokinetic parameter(Up to 24 months)
- Part 1 and Part 3 : Best Overall Response (BOR)(Up to 24 months)
- All parts : Duration of Response (DoR)(Up to 24 months)
- Part 2 and Part 3 : Progression-Free Survival (PFS)(Up to 24 months)
- Part 2 and Part 3 : Overall Survival (OS)(Up to 24 months)