Safety, Tolerability, Efficacy, Pharmacokinetics Profile and Immunogenicity of HS-20117 in Combination With Other Drugs in Advanced Solid Tumors, a Phase Ib Clinical Trial
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 780
- 试验地点
- 1
- 主要终点
- Tolerability of HS-20117 combination therapy: incidence of DLT events, maximum tolerated dose (MTD) or maximum applicable dose (MAD) of HS-20117 in combination therapies.
研究概览
简要总结
HS-20117 is a fully-human EGFR-MET immunoglobulin G1(IgG1)-like bispecific antibody. The purpose of study is to evaluate the safety, tolerability, efficacy, PK profile and immunogenicity of HS-20117 in combination with other drugs in advanced solid tumors.
详细描述
This is a multicenter, open-label, Phase Ib clinical trial of HS-20117 combination therapies to evaluate the safety, tolerability, efficacy, PK profile and immunogenicity in participants with advanced solid tumors. The study includes a dose escalation part and a dose expansion part. The dose-escalation study will be performed to evaluate the safety, tolerability, PK profile, immunogenicity, and efficacy of HS-20117 combination therapies in participants with advanced solid tumor. The subsequent dose-expansion study will be performed to evaluate the efficacy of HS-20117 combination therapies in participants with locally advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations or EGFR classical mutations, and RAS/BRAF V600E wild type CRC.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or females aged 18 - 75 years (inclusive).
- •Histologically confirmed unresectable, recurrent or metastatic solid tumors.
- •At least one target lesion per the RECIST v1.
- •ECOG performance status of 0-
- •Minimum life expectancy > 12 weeks.
- •Males or Females should be using adequate contraceptive measures throughout the study.
- •Females must not be pregnant at screening or have evidence of non-childbearing potential.
- •Signed Informed Consent Form.
排除标准
- •Received or are receiving the following treatments:
- •Any anticancer therapy targeting MET, including TKIs, antibodies or antibody-drug conjugates.
- •Monoclonalor bispecific antibodies targeting EGFR.
- •Systemic anti-cancer treatment (Cytotoxicities and anti-cancer Traditional Chinese medicine or TKIs) within 2 weeks prior to the first dose of HS-
- •Investigational anti-cancer drugs or antibodies or ADCs within 4 weeks prior to the first dose of HS-
- •Local radiotherapy within 2 weeks prior to the first dose of HS-20117, more than 30% of bone marrow irradiation or large-area radiotherapy within 4 weeks before the first dose of HS-
- •Presence of pleural effusion/ascites requiring clinical intervention; presence of pericardial effusion.
- •Major surgery within 4 weeks prior to the first dose of HS-
- •Presence of Grade ≥ 2 toxicities due to prior anti-tumor therapy.
- •Presence of uncured secondary primary malignancies.
- •Untreated, or active central nervous system metastases.
- •Severe, uncontrolled or active cardiovascular disorders.
- •Serious infection within 4 weeks prior to the first dose of HS-20117.
研究组 & 干预措施
Cohort 1a
NSCLC
干预措施: HS-20117 combined Platinum-containing chemotherapy (Drug)
Cohort 2a
NSCLC
干预措施: HS-20117 combined HS-20093 (Drug)
Cohort 3a
CRC
干预措施: HS-20117+CAPEOX (Drug)
Cohort 4a
CRC
干预措施: HS-20117+FOLFIRI (Drug)
Cohort 5a
CRC
干预措施: HS-20117+mFOLFOX6 (Drug)
Cohort 6a
CRC
干预措施: HS-20117 combined HS-20093 and 5-FU (Drug)
结局指标
主要结局
Tolerability of HS-20117 combination therapy: incidence of DLT events, maximum tolerated dose (MTD) or maximum applicable dose (MAD) of HS-20117 in combination therapies.
时间窗: From the date of first dose to day 21.
MTD is defined as the previous dose level at which 2 or more out of 2-6 subjects experienced a DLT. MAD is defined as follows: a) based on PK data, it is anticipated that at this dose level, the dose-exposure plateau has been reached, b) based on existing safety data, it is judged that dose escalation following this dose level will have a large safety risk or subject intolerance, or c) based on the PK-PD model, it suggested that the optimal target concentration of safety and efficacy has been explored.
Incidence and severity of treatment-emergent adverse events
时间窗: rom the date of first dose to 90 days after the final dose.
Adverse event (assessed according to NCI CTCAE v5.0) is defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
次要结局
- Efficacy of HS-20117: Objective response rate (ORR)(From the date of first dose to the date of disease progression or withdrawal from study, approximately 2 years)
- PK parameters: Maximum serum concentration (Cmax) of HS-20117 and HS-20093.(From the date of first dose to 90 days after the final dose.)
- Efficacy of HS-20117: disease control rate (DCR)(From the date of first dose to the date of disease progression or withdrawal from study, approximately 2 years)
- Efficacy of HS-20117: duration of response (DoR)(From the date of first dose to the date of disease progression or withdrawal from study, approximately 2 years)
- Efficacy of HS-20117: progression free survival (PFS)(From the date of first dose to the date of disease progression or withdrawal from study, approximately 2 years)
- Efficacy of HS-20117: overall survival (OS)(From the date of first dose to the date of disease progression or withdrawal from study, approximately 2 years)
- PK parameters: Trough serum concentration (Ctrough) of HS-20117 and HS-20093(From the date of first dose to 90 days after the final dose.)
- PK parameters: Time to reach maximum observed serum concentration (Tmax) of HS-20117(From the date of first dose to 90 days after the final dose.)
- PK parameters: Area under the curve from time Zero to end of dosing interval (AUCtau) of HS-20117(From the date of first dose to 90 days after the final dose.)
- Immunogenicity of HS-20117(From the date of first dose to 90 days after the final dose.)