A Clinical Trial of LBL-024 Combined With Etoposide and Platinum in Patients With Advanced Neuroendocrine Carcinoma

Study Overview
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Brief Summary
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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
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This trial includes two parts: phase Ib and phase II study. Phase Ib is a dose-escalation phase and Phase II is a dose-expansion phase. 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 program to enroll approximately 50 patients with advanced neuroendocrine carcinoma without systemic treatment. This trial will enroll 68 patients in Phase Ib and Phase II study.

Official Title
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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)

Conditions
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Advanced Neuroendocrine Carcinoma

Intervention / Treatment
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* Drug: LBL-024 for Injection
* Drug: Etoposide Injection
* Drug: Cisplatin for Injection
* Drug: Carboplatin Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LBL-024+Etoposide+Cisplatin/Carboplatin<br>LBL-024+Etoposide+Cisplatin/Carboplatin Injection , dose A or dose B; Q3w | Drug: LBL-024 for Injection<br>* Initial dose - MTD; Q3W; intravenous infusion<br>* Other names: LBL-024;Drug: Etoposide Injection<br>* Initial dose; Q3W; intravenous infusion<br>* Other names: Etoposide;Drug: Cisplatin for Injection<br>* Initial dose; Q3W; intravenous infusion<br>* Other names: Cisplatin;Drug: Carboplatin Injection<br>* Initial dose; Q3W; intravenous infusion<br>* Other names: Carboplatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | 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 . | From all subjects signed the informed consent form up to the completion of the follow-up period of drug withdrawal (30 days after drug withdrawal or before the start of new anti-tumor therapy). | 
| Dose-limiting toxicities（DLT） | 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. | Within 3 weeks after receiving the first dose of the test drug (DLT assessment for subjects in dose escalation phase). | 
| Maximum tolerated dose (MTD) | 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 . | Within 3 weeks after receiving the first dose of the test drug (MTD assessment for subjects in dose escalation phase). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Maximum serum concentration | From all subjects signed the informed consent form up to the completion of the follow-up period of drug withdrawal (30 days after drug withdrawal or before the start of new anti-tumor therapy | 
| Tmax | After taking a single dose, Time to reach maximum plasma concentration | From all subjects signed the informed consent form up to the completion of the follow-up period of drug withdrawal (30 days after drug withdrawal or before the start of new anti-tumor therapy | 
| immunogenicity | The immunogenicity is evaluated by the incidence of anti-drug antibodies (ADA) and neutralizing antibodies (if applicable) in subjects | From all subjects signed the informed consent form up to the completion of the follow-up period of drug withdrawal (30 days after drug withdrawal or before the start of new anti-tumor therapy | 
| Duration of Response(DOR） | The period from the participants first achieving CR or PR to disease progression. | From all subjects signed the informed consent form up to the completion of the follow-up period of drug withdrawal (30 days after drug withdrawal or before the start of new anti-tumor therapy |