A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of HS-20117 in Participants With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 322
- 试验地点
- 1
- 主要终点
- [Phase 1a] Maximum tolerated dose (MTD) of HS-20117
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, pharmacokinetics (PK), and preliminary efficacy of HS-20117 as a monotherapy for participants with advanced solid tumors.
详细描述
This is a multicenter, open-label, Phase I clinical study of HS-20117 to evaluate the safety, tolerability, PK, immunogenicity and efficacy in participants with advanced solid tumors. The study consists of phase Ia (dose escalation) and phase Ib (dose expansion). The dose-escalation study will be performed to evaluate the safety, tolerability, PK profile, immunogenicity, and efficacy of HS-20117 in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. The subsequent dose-expansion study will be performed to evaluate the efficacy of HS-20117 in participants with locally advanced or metastatic NSCLC who have progressed after prior platinum-based chemotherapy or are intolerant to platinum-based chemotherapy with EGFR exon 20 insertion mutations, and to explore the efficacy of HS-20117 in participants with other advanced solid tumors.
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
- 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).
- •For the phase Ia study: Participants with locally advanced or metastatic NSCLC (stage IIIB/IIIC/IV) with EGFR-activating mutations who have progressed after or are intolerant to or not available to standard of care (SoC).
- •For the phase Ib study:
- •Cohort A: Participants with locally advanced or metastatic NSCLC (stage IIIB/IIIC/IV) with EGFR exon 20ins mutations who have progressed after prior platinum-based chemotherapy or are intolerant to platinum-based chemotherapy.
- •Cohort B: Participants with other advanced solid tumors who have progressed after prior SoC or are intolerant to SoC.
- •Agree to provide fresh or archival tumor tissue.
- •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.
- •Have signed Informed Consent Form.
排除标准
- •Received or are receiving the following treatments:
- •For the phase Ib study Cohort A: Previous or current treatment with EGFR exon 20ins targeted therapy.
- •Traditional Chinese medicine indicated for tumors within 2 weeks prior to the first dose of HS-
- •Cytotoxic chemotherapies, investigational drugs or other systematic anti-tumor therapies within 3 weeks prior to the first dose of HS-
- •Antibodies 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.
- •History of other primary malignancies.
- •Untreated, or active central nervous system metastases.
- •Inadequate bone marrow reserve or organ functions.
- •Severe, uncontrolled or active cardiovascular disorders.
- •Severe or uncontrolled systemic diseases.
- •Severe bleeding symptoms or bleeding tendencies within 1 month prior to the first dose of HS-
- •Severe arteriovenous thrombosis occurred within 3 months prior to the first dose of HS-20117
- •Serious infection within 4 weeks prior to the first dose of HS-
- •Active infectious diseases.
- •Interstitial lung disease (ILD).
- •Serious neurological or mental disorders.
- •History of hypersensitivity to any component of HS-20117 or similar drugs.
- •Participants with any condition that compromises the safety of the participant or interferes with the assessment of the study, as judged by the investigator.
研究组 & 干预措施
HS-20117
Participants will receive IV infusion of HS-20117 once during cycle 1 and once every 2 weeks during subsequent cycles (The duration of each treatment cycle is 28 days)
干预措施: HS-20117 (Drug)
结局指标
主要结局
[Phase 1a] Maximum tolerated dose (MTD) of HS-20117
时间窗: Cycle 1 (28 days)
MTD is defined as the previous dose level at which 2 or more out of 2-6 subjects experienced a DLT.
[Phase 1b] Efficacy of HS-20117: Objective response rate (ORR)
时间窗: From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years
ORR is defined as the percentage of participants with BOR of confirmed CR or confirmed PR per RECIST v1.1
[Phase 1a] Maximum applicable dose (MAD) of HS-20117
时间窗: Cycle 1 (28 days)
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.
次要结局
- [phase 1a and 1b] Incidence and severity of treatment-emergent adverse events(From the date of first dose until 90 days after the final dose. A cycle is 28 days)
- [phase 1a and 1b] PK parameters: Maximum serum concentration (Cmax) of HS-20117(From the date of first dose until 30 days after the final dose. A cycle is 28 days.)
- [phase 1a and 1b] PK parameters: Trough serum concentration (Ctrough) of HS-20117(From the date of first dose until 30 days after the final dose. A cycle is 28 days.)
- [phase 1a and 1b] PK parameters: Time to reach maximum observed serum concentration (Tmax) of HS-20117(From the date of first dose until 30 days after the final dose. A cycle is 28 days)
- [phase 1a] PK parameters: Area under the curve from time Zero to end of dosing interval (AUCtau) of HS-20117(From the date of first dose until 30 days after the final dose. A cycle is 28 days.)
- [phase 1a] PK parameters: Terminal elimination half-life (t1/2) of HS-20117(From the date of first dose until 30 days after the final dose. A cycle is 28 days.)
- [phase 1a] Efficacy of HS-20117: ORR(From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years.)
- [phase 1a and 1b] Efficacy of HS-20117: disease control rate (DCR)(From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years.)
- [phase 1a and 1b] Efficacy of HS-20117: duration of response (DoR)(From the date of CR, PR until the date of disease progression or death, approximately 2 years.)
- [phase 1a and 1b] Efficacy of HS-20117: progression free survival (PFS)(From the date of randomization or first dose (if randomization is not needed) until the date of disease progression or death, approximately 2 years.)
- [phase 1b] Efficacy of HS-20117: overall survival (OS)(From the date of randomization or first dose (if randomization is not needed) until the documentation of death from any cause, approximately 4 years)
- [phase 1a and 1b] Immunogenicity of HS-20117(Cycle 1 Day 1: predose through EOT or follow up period (90 days after the last dose).)