An Open-label, Multicenter Phase Ib/II Clinical Study to Evaluate the Safety and Efficacy of LBL-024 Combined With Etoposide and Platinum in the First-line Treatment of Patients With Advanced Neuroendocrine Carcinoma (NEC)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 178
- 试验地点
- 34
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
An open-label, multicenter phase Ib/II clinical study to evaluate the safety and efficacy of LBL-024 combined with etoposide and platinum in the first-line treatment of patients with advanced neuroendocrine carcinoma (NEC)
详细描述
This trial includes two parts: phase Ib and phase II study. Phase Ib is a dose-escalation and Phase II is the dose optimization and dose expansion .
Phase Ib program to enroll patients with advanced neuroendocrine carcinoma (NEC) without systemic therapy.To sequentially evaluate the safety and tolerability of LBL-024 in combination with etoposide and platinum (cisplatin or carboplatin) at different doses by the dose-escalation method.
Phase II includes two stages, dose optimization and dose expansion.
The dose optimization part will conduct combination of LBL-024, which is a further optimization study in two dose groups, enrolling patients with EP-NEC who have not received systemic treatment, to fully assess the dose-exposure-effect relationship, and in combination with the target binding characteristics of LBL-024, pharmacokinetic/pharmacodynamic, efficacy and/or safety profile, considering multiple dimensions,To confirm the rationale for the recommended Phase 2 dose (RP2D).
The dose expansion:the recommended Phase 2 dose (RP2D) will be determined based on the safety, tolerability, efficacy and PK data from the clinical studies of LBL-024.After obtaining the RP2D, a dose expansion study of combination dosing at the RP2D will be conducted to obtain adequate efficacy data.
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
- •Agree to follow the trial treatment regimen and visit schedule, voluntarily enroll, and sign the written informed consent.
- •aged 18-75 years (including borderline values) at the time of signing the informed consent form
- •The Eastern Cooperative Oncology Group's physical status scoring standard (ECOG) is 0~
- •The expected survival time is at least 12 weeks.
- •According to the evaluation of RECIST 1.1 （Response Evaluation Criteria in Solid Tumours），the subjects enrolled have at least one measurable target lesion.
- •Fertile men and women of childbearing age are willing to take effective contraceptive measures from the signing of the informed consent form to 6 months after the last dose of the investigational drug; women of childbearing age include premenopausal women and women who had menopause less than two years ago. Blood pregnancy test results must be negative for women of childbearing age within 7 days prior to the initial dose of the investigational drug.
排除标准
- •Subjects who underwent major organ surgery (excluding needle biopsy) or significant trauma within 4 weeks prior to the initial use of the investigational drug, or require elective surgery during the trial period
- •Use of immunomodulatory drugs within 14 days prior to the initial use of the investigational drug, including but not limited to thymosin, interleukin, and interferon
- •Subjects with an active infection that currently requires intravenous anti-infective therapy.
- •Clinically uncontrollable pleural effusion, pericardial effusion, and requiring repeated drainage or medical intervention.
- •medical history of immunodeficiency including HIV antibody positive.
- •Pregnant or lactating women.
- •The investigator believes that the subject has other conditions that may affect compliance or that are not suitable for participating in this study.
研究组 & 干预措施
Atezolizumab+Etoposide+Carboplatin
Atezolizumab+Etoposide+Carboplatin
Intravenous infusion.
干预措施: Etoposide Injection (Drug)
Atezolizumab+Etoposide+Carboplatin
Atezolizumab+Etoposide+Carboplatin
Intravenous infusion.
干预措施: Carboplatin Injection (Drug)
Atezolizumab+Etoposide+Carboplatin
Atezolizumab+Etoposide+Carboplatin
Intravenous infusion.
干预措施: Atezolizumab injection (Drug)
LBL-024+Etoposide+Carboplatin/Cisplatin
LBL-024+Etoposide+Carboplatin/Cisplatin
Intravenous infusion.
干预措施: LBL-024 for Injection (Drug)
LBL-024+Etoposide+Carboplatin/Cisplatin
LBL-024+Etoposide+Carboplatin/Cisplatin
Intravenous infusion.
干预措施: Etoposide Injection (Drug)
LBL-024+Etoposide+Carboplatin/Cisplatin
LBL-024+Etoposide+Carboplatin/Cisplatin
Intravenous infusion.
干预措施: Carboplatin Injection (Drug)
LBL-024+Etoposide+Carboplatin/Cisplatin
LBL-024+Etoposide+Carboplatin/Cisplatin
Intravenous infusion.
干预措施: Cisplatin injection (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: From all subjects signed the informed consent form up to the completion of the follow-up period of drug withdrawal (28 days after drug withdrawal or before the start of new anti-tumor therapy).
ORR (including the rates of complete response (CR) and partial response (PR)), evaluated based on the RECIST 1.1, refers to the percentage of study subjects who achieve a complete response or partial response. It was used to evaluate the efficacy in Phase II .
Dose-limiting toxicities（DLT）
时间窗: Within 3 weeks after receiving the first dose of the test drug (DLT assessment for subjects in dose escalation phase).
DLT describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment. It was used to evaluate the safety in Phase Ib.
Maximum tolerated dose (MTD)
时间窗: Within 3 weeks after receiving the first dose of the test drug (MTD assessment for subjects in dose escalation phase).
MTD is defined as the hightest dose level at which no more than 1 out of 6 subjects experiences a DLT during the first cycles. It was used to evaluate the tolerability in Phase Ib .
Progression-Free Survival(PFS)
时间窗: From all subjects signed the informed consent form up to the completion of the follow-up period of drug withdrawal (28 days after drug withdrawal or before the start of new anti-tumor therapy).
PFS is defined as the time from randomization to disease progression or death from any cause.It was used to evaluate the efficacy in Phase II .
Occurrence of adverse event (AE) and serious adverse event (SAE)
时间窗: From all subjects signed the informed consent form up to the completion of the follow-up period of drug withdrawal (90 days after drug withdrawal or before the start of new anti-tumor therapy)
Adverse event (AE) will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 5.0.The safety profile of LBL-024 Combination Administration will be assessed by monitoring the adverse event (AE) and serious adverse event (SAE) in Phase Ib study.
The recommended Phase 2 dose (RP2D)
时间窗: From all subjects signed the informed consent form up to the completion of the follow-up period of drug withdrawal (28 days after drug withdrawal or before the start of new anti-tumor therapy).
The recommended Phase 2 dose (RP2D) will be determined comprehensively based on the safety, tolerability, efficacy and PK data from the clinical studies of LBL-024 in advance.
次要结局
- Cmax(From all subjects signed the informed consent form up to the completion of the follow-up period of drug withdrawal (28 days after drug withdrawal or before the start of new anti-tumor therapy)
- Tmax(From all subjects signed the informed consent form up to the completion of the follow-up period of drug withdrawal (28 days after drug withdrawal or before the start of new anti-tumor therapy)
- immunogenicity(From all subjects signed the informed consent form up to the completion of the follow-up period of drug withdrawal (28 days after drug withdrawal or before the start of new anti-tumor therapy)
- Duration of Response(DOR）(From all subjects signed the informed consent form up to the completion of the follow-up period of drug withdrawal (28 days after drug withdrawal or before the start of new anti-tumor therapy)
- Disease Control Rate(DCR)(From all subjects signed the informed consent form up to the completion of the follow-up period of drug withdrawal (28 days after drug withdrawal or before the start of new anti-tumor therapy))