A Phase Ib/III Clinical Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Immunogenicity of HS-20117 Combined With Aumolertinib in Participants With Advanced Non-Squamous Non-Small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 1,080
- 试验地点
- 2
- 主要终点
- [Phase Ib] Objective response rate (ORR) According to response evaluation criteria in solid tumors (RECIST) v1.1 by Investigators (INVs)
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 this study is to assess the safety, efficacy, pharmacokinetics and immunogenicity of HS-20117 combined with Aumolertinib in participants with epidermal growth factor receptor (EGFR) mutation (Exon 19 deletions [Exon 19del] or Exon 21 L858R substitution) positive, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC).
详细描述
This is a multicenter Phase Ib/III clinical study evaluating the safety, efficacy, pharmacokinetics (PK), and immunogenicity of HS-20117 in combination with aumolertinib in subjects with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC). The study is divided into two phases, Phase Ib, a dose expansion study and Phase III, a confirmatory study. In the dose expansion phase (Phase Ib), HS-20117 will first be studied in combination with the standard dose of aumolertinib, to assess the efficacy, safety, tolerability, PK profile, and immunogenicity of HS-20117 in combination with aumolertinib in the target population, as well as to determine the recommended Phase III dose (RP3D). Following confirmation of the safety and efficacy of HS-20117 in combination with aumolertinib and RP3D in Phase Ib, a randomized, active-controlled, open-label, multicenter Phase III study will be initiated to assess the efficacy and safety of HS-20117 in combination with aumolertinib versus aumolertinib in the target population in the confirmatory study phase.
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 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).
- •Participants with newly diagnosed histologically or cytologically confirmed, locally advanced or metastatic EGFR-sensitive mutated NSCLC (stage IIIB/IIIC/IV) that is treatment naive and not amenable to curative therapy including surgical resection or chemoradiation.
- •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:
- •Previous or current treatment with MET targeted therapy or EGFR targeted antibodies or antibody-drug conjugates (ADC).
- •Traditional Chinese medicine indicated for tumors, major surgery or other local therapy within washout period to the first dose of study drug.
- •Presence of pleural effusion/ascites requiring clinical intervention; presence of pericardial effusion.
- •Other investigational non-anti-tumor drugs, strong CYP3A4 inhibitors, strong inducers, drugs that are sensitive substrates of BCRP or P-gp, or drugs that prolong the QT interval within the washout period.
- •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.
- •Severe arteriovenous thrombosis occurred.
- •Serious or active infection.
- •Active infectious diseases.
- •Interstitial lung disease (ILD).
- •Serious neurological or mental disorders.
- •History of hypersensitivity to any component of HS-20117 and Aumolertinib or their similar drugs.
- •Female subjects who are pregnant, lactating, or planning to become pregnant or breastfeed during the study period or within 6 months after the last dose of the study drug.
- •Subjects with a history of severe allergic reactions or those who have experienced severe infusion reactions
- •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
Phase Ib: HS-20117 and Aumolertinib
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) at exploratory doses. Aumolertinib will be administered 110 mg orally once daily.
干预措施: HS-20117 (Drug)
Phase Ib: HS-20117 and Aumolertinib
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) at exploratory doses. Aumolertinib will be administered 110 mg orally once daily.
干预措施: Aumolertinib (Drug)
Phase III: HS-20117 and Aumolertinib
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) at exploratory doses. Aumolertinib will be administered 110 mg orally once daily.
干预措施: HS-20117 (Drug)
Phase III: HS-20117 and Aumolertinib
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) at exploratory doses. Aumolertinib will be administered 110 mg orally once daily.
干预措施: Aumolertinib (Drug)
Phase III: Aumolertinib
Participants will receive Aumolertinib 110 mg orally once daily.
干预措施: Aumolertinib (Drug)
结局指标
主要结局
[Phase Ib] Objective response rate (ORR) According to response evaluation criteria in solid tumors (RECIST) v1.1 by Investigators (INVs)
时间窗: From the date of first dose until the date of disease progression or withdrawal from study, up to approximately 40 months
ORR is defined as the percentage of participants with DOR of confirmed CR or confirmed PR per RECIST v1.1
[Phase III] Progression-Free Survival (PFS) According to RECIST v1.1 by Independent Review Committee(IRC)
时间窗: Up to approximately 40 months
PFS is defined as the time from randomization until the date of objective disease progression or death, whichever occurred first, based on IRC using RECIST v1.1
次要结局
- [Phase Ib and III] Overall Survival (OS)(Approximately 60 months)
- [Phase Ib] 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 Ib and III] Duration of response (DoR) According to RECIST v1.1 by INVs(From the date of CR, PR until the date of disease progression or death, approximately 40 months.)
- [Phase III] ORR According to RECIST v1.1 by INVs(From the date of first dose until the date of disease progression or withdrawal from study, up to approximately 40 months)
- [Phase III] ORR According to RECIST v1.1 by IRC(From the date of first dose until the date of disease progression or withdrawal from study, up to approximately 40 months)
- [Phase Ib and III] Disease control rate (DCR) According to RECIST v1.1 by INVs(From the date of first dose until the date of disease progression or withdrawal from study, approximately 40 months.)
- [Phase Ib and III] Progression-Free Survival (PFS) According to RECIST v1.1 by INVs(Up to approximately 40 months)
- [Phase III] DCR According to RECIST v1.1 by IRC(From the date of first dose until the date of disease progression or withdrawal from study, approximately 40 months.)
- [Phase III] DoR According to RECIST v1.1 by IRC(From the date of CR, PR until the date of disease progression or death, approximately 40 months.)
- [Phase Ib and III] 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 Ib and III] Immunogenicity of HS-20117(Cycle 1 Day 1: predose through EOT or follow up period (90 days after the last dose).)
- [Phase Ib] 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 Ib] 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 Ib] 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 Ib] 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.)