Advanced Neuroendocrine Carcinoma
Conditions
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 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. This trial will enroll 178 patients in Phase Ib and Phase II study.
Interventions
intravenous infusion
intravenous infusion
DRUGCarboplatin Injection
intravenous infusion
intravenous infusion
DRUGCisplatin injection
intravenous infusion
Sponsors
Nanjing Leads Biolabs Co.,Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Agree to follow the trial treatment regimen and visit schedule, voluntarily enroll, and sign the written informed consent. 2. aged 18-75 years (including borderline values) at the time of signing the informed consent form 3. The Eastern Cooperative Oncology Group's physical status scoring standard (ECOG) is 0\~1. 4. The expected survival time is at least 12 weeks. 5. According to the evaluation of RECIST 1.1 （Response Evaluation Criteria in Solid Tumours），the subjects enrolled have at least one measurable target lesion. 6. 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.
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. Subjects with an active infection that currently requires intravenous anti-infective therapy. 4. Clinically uncontrollable pleural effusion, pericardial effusion, and requiring repeated drainage or medical intervention. 5. medical history of immunodeficiency including HIV antibody positive. 6. Pregnant or lactating women. 7. The investigator believes that the subject has other conditions that may affect compliance or that are not suitable for participating in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 . |
| Occurrence of adverse event (AE) and serious adverse event (SAE) | 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) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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) | Percentage of participants achieving CR, PR, iCR, iPR and stable disease (SD) after treatment. |
Countries
China
Contacts
CONTACTlin shen
PRINCIPAL_INVESTIGATORlin shen
Peking University Cancer Hospital & Institute
Outcome results
None listed