Clinical trial NCT06157827: A Clinical Trial of LBL-024 Combined With Etoposide and Platinum in Patients With Advanced Neuroendocrine Carcinoma
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Neuroendocrine Carcinoma
Lead sponsor: Nanjing Leads Biolabs Co.,Ltd
Sponsor class: INDUSTRY
First posted: 2023-12-06
Enrollment: 178
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Subject has voluntarily agreed to participate by giving written informed consent for the trial，and Consent to follow trial treatment and visit schedule
2. aged 18-75 years (including borderline values) at the time of signing the informed consent form
3. Have a performance status of 0 to 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status Scale
4. Have a life expectancy of at least 12 weeks
5. Subject has at least one measurable target lesion by RECIST 1.1 criteria
6. 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:

1. 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
2. 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
3. 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)
4. Subjects with an active infection that currently requires intravenous anti infective therapy
5. History of immunodeficiency, including positive HIV antibody test results
6. Pregnant or lactating women
7. 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.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 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).
measure: Dose-limiting toxicities（DLT）
timeFrame: Within 3 weeks after receiving the first dose of the test drug (DLT assessment for subjects in dose escalation phase).
measure: Maximum tolerated dose (MTD)
timeFrame: Within 3 weeks after receiving the first dose of the test drug (MTD assessment for subjects in dose escalation phase).
measure: Progression-Free Survival(PFS)
timeFrame: 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).
Secondary outcomes:
measure: Cmax
timeFrame: 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
measure: Tmax
timeFrame: 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
measure: immunogenicity
timeFrame: 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
measure: Duration of Response(DOR）
timeFrame: 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
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Hefei
country: China
facility: Anhui Cancer Hospital
state: Anhui
city: Beijing
country: China
facility: Beijing GoBroad Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangdong Pharmaceutical University
state: Guangdong
city: Nanning
country: China
facility: Guangxi Medical University Cancer Hospital
state: Guangxi
city: Ha'erbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan University of Science and Technology
state: Henan
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Xiangyang
country: China
facility: Xiangyang Central Hospital
state: Hubei
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Shenyang
country: China
facility: Liaoning Cancer Hospital
state: Liaoning
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Cancer hospital
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Hangzhou
country: China
facility: The First Affiliated Hospital Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: The Second Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital，Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: lin shen
role: PRINCIPAL_INVESTIGATOR
References: