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)
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
178
Initial dose-MTD; Q3W; intravenous infusion
Initial dose(Dose was decided by the investigator according to the subject's condition); Q3W; intravenous infusion
Initial dose(Dose was decided by the investigator according to the subject's condition); Q3W; intravenous infusion
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 .
Time frame: 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).
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.
Time frame: 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 .
Time frame: Within 3 weeks after receiving the first dose of the test drug (MTD assessment for subjects in dose escalation phase).
Progression-Free Survival(PFS)
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 .
Time frame: 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).
Cmax
Maximum serum concentration
Time frame: 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
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Initial dose; Q3W; intravenous infusion
Initial dose(Dose was decided by the investigator according to the subject's condition); Q3W; intravenous infusion
Anhui Provincial Hospital
Hefei, Anhui, China
RECRUITINGAnhui Cancer Hospital
Hefei, Anhui, China
RECRUITINGBeijing GoBroad Hospital
Beijing, Beijing Municipality, China
RECRUITINGBeijing Cancer Hospital
Beijing, Beijing Municipality, China
RECRUITINGChongqing University Cancer Hospital
Chongqing, Chongqing Municipality, China
RECRUITINGFujian Cancer Hospital
Fuzhou, Fujian, China
RECRUITINGThe First Affiliated Hospital of Guangdong Pharmaceutical University
Guangzhou, Guangdong, China
RECRUITINGGuangxi Medical University Cancer Hospital
Nanning, Guangxi, China
RECRUITINGHarbin Medical University Cancer Hospital
Harbin, Heilongjiang, China
RECRUITINGThe First Affiliated Hospital of Henan University of Science and Technology
Luoyang, Henan, China
RECRUITING...and 14 more locations
Tmax
After taking a single dose, Time to reach maximum plasma concentration
Time frame: 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
The immunogenicity is evaluated by the incidence of anti-drug antibodies (ADA) and neutralizing antibodies (if applicable) in subjects
Time frame: 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)
The period from the participants first achieving CR or PR to disease progression.
Time frame: 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