A Clinical Trial of LBL-024 Combined With Etoposide and Platinum in Patients With Advanced Neuroendocrine Carcinoma
- Conditions
- Advanced Neuroendocrine Carcinoma
- Interventions
- Registration Number
- NCT06157827
- Lead Sponsor
- Nanjing Leads Biolabs Co.,Ltd
- Brief Summary
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)
- Detailed Description
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 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.
This trial will enroll 178 patients in Phase Ib and Phase II study.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 178
- Subject has voluntarily agreed to participate by giving written informed consent for the trial，and Consent to follow trial treatment and visit schedule
- aged 18-75 years (including borderline values) at the time of signing the informed consent form
- Have a performance status of 0 to 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status Scale
- Have a life expectancy of at least 12 weeks
- Subject has at least one measurable target lesion by RECIST 1.1 criteria
- Fertile men and women of childbearing age are willing to take effective contraceptive measures (including abstinence, intrauterine devices, hormonal contraception, and correct use of condoms) 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.
- 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
- Systemic use of corticosteroidsor other immunosuppressants within 14 days prior to the initial use of the investigational drug;The following conditions are excluded: Treatment with topical, ocular, intra-articular, intranasal, and inhaled corticosteroids; short-term use of glucocorticoids for preventive therapy (e.g., to prevent contrast allergy)
- Subjects with an active infection that currently requires intravenous anti infective therapy
- History of immunodeficiency, including positive HIV antibody test results
- Pregnant or lactating women
- The investigator's assessment that there may be other factors affecting compliance among participants or that some may not be suitable for inclusion in this study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description LBL-024+Etoposide+Carboplatin/Cisplatin Etoposide Injection LBL-024+Etoposide+Carboplatin/Cisplatin Injection，dose A、dose B or dose C; Q3W LBL-024+Etoposide+Carboplatin/Cisplatin Carboplatin Injection LBL-024+Etoposide+Carboplatin/Cisplatin Injection，dose A、dose B or dose C; Q3W Atezolizumab+Etoposide+Carboplatin Carboplatin Injection Atezolizumab+Etoposide+Carboplatin Injection，dose A ; Q3W LBL-024+Etoposide+Carboplatin/Cisplatin Cisplatin injection LBL-024+Etoposide+Carboplatin/Cisplatin Injection，dose A、dose B or dose C; Q3W Atezolizumab+Etoposide+Carboplatin Etoposide Injection Atezolizumab+Etoposide+Carboplatin Injection，dose A ; Q3W LBL-024+Etoposide+Carboplatin/Cisplatin LBL-024 for Injection LBL-024+Etoposide+Carboplatin/Cisplatin Injection，dose A、dose B or dose C; Q3W Atezolizumab+Etoposide+Carboplatin Atezolizumab injection Atezolizumab+Etoposide+Carboplatin Injection，dose A ; Q3W
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) 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） 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) 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) 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 .
- Secondary Outcome Measures
Name Time Method 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 Maximum serum concentration
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 After taking a single dose, Time to reach maximum plasma concentration
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 The immunogenicity is evaluated by the incidence of anti-drug antibodies (ADA) and neutralizing antibodies (if applicable) in subjects
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 The period from the participants first achieving CR or PR to disease progression.
Trial Locations
- Locations (24)
Qilu Hospital of Shandong University
🇨🇳Jinan, Shandong, China
Harbin Medical University Cancer Hospital
🇨🇳Ha'erbin, Heilongjiang, China
Shanxi Cancer hospital
🇨🇳Taiyuan, Shanxi, China
The First Affiliated Hospital of Henan University of Science and Technology
🇨🇳Luoyang, Henan, China
Shandong Cancer Hospital
🇨🇳Jinan, Shandong, China
The First Affiliated Hospital Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
Chongqing University Cancer Hospital
🇨🇳Chongqing, Chongqing, China
The First Affiliated Hospital of Guangdong Pharmaceutical University
🇨🇳Guangzhou, Guangdong, China
Hubei Cancer Hospital
🇨🇳Wuhan, Hubei, China
Guangxi Medical University Cancer Hospital
🇨🇳Nanning, Guangxi, China
Liaoning Cancer Hospital
🇨🇳Shenyang, Liaoning, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, Shanghai, China
West China Hospital of Sichuan University
🇨🇳Chengdu, Sichuan, China
The Second Affiliated Hospital, Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, Zhejiang, China
Anhui Cancer Hospital
🇨🇳Hefei, Anhui, China
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China
The First Affiliated Hospital of Nanchang University
🇨🇳Nanchang, Jiangxi, China
Xiangyang Central Hospital
🇨🇳Xiangyang, Hubei, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Sir Run Run Shaw Hospital，Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
Anhui Provincial Hospital
🇨🇳Hefei, Anhui, China
Beijing GoBroad Hospital
🇨🇳Beijing, Beijing, China
Fujian Cancer Hospital
🇨🇳Fuzhou, Fujian, China