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)

Overview

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

• Drug LBL-024 for Injection
  intravenous infusion
• Drug Etoposide Injection
  intravenous infusion
• Drug Carboplatin Injection
  intravenous infusion
• Drug Atezolizumab injection
  intravenous infusion
• Drug Cisplatin injection
  intravenous infusion

Primary outcome measures

• Objective Response Rate (ORR) [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） [Time frame: Within 3 weeks after receiving the first dose of the test drug (DLT assessment for subjects in dose escalation phase).]
• Progression-Free Survival(PFS) [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).]
• Occurrence of adverse event (AE) and serious adverse event (SAE) [Time frame: 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)]
• The recommended Phase 2 dose (RP2D) [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).]

Secondary outcome measures (5)

• Cmax [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]
• Tmax [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 [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） [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]
• Disease Control Rate(DCR) [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)]

Eligibility criteria

Inclusion criteria

• Agree to follow the trial treatment regimen and visit schedule, voluntarily enroll, and sign the written informed consent.
• aged 18-75 years (including borderline values) at the time of signing the informed consent form
• The Eastern Cooperative Oncology Group's physical status scoring standard (ECOG) is 0\~1.
• The expected survival time is at least 12 weeks.
• According to the evaluation of RECIST 1.1 （Response Evaluation Criteria in Solid Tumours），the subjects enrolled have at least one measurable target lesion.
• 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

• 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
• Subjects with an active infection that currently requires intravenous anti-infective therapy.
• Clinically uncontrollable pleural effusion, pericardial effusion, and requiring repeated drainage or medical intervention.
• medical history of immunodeficiency including HIV antibody positive.
• Pregnant or lactating women.
• The investigator believes that the subject has other conditions that may affect compliance or that are not suitable for participating in this study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 25 centers

• Anhui Provincial Hospital — Hefei
• Anhui Cancer Hospital — Hefei
• Beijing GoBroad Hospital — Beijing
• Beijing Cancer Hospital — Beijing
• Chongqing University Cancer Hospital — Chongqing
• Fujian Cancer Hospital — Fuzhou
• Sun Yat-sen University Cancer Center (SYSUCC) — Guangzhou
• The First Affiliated Hospital of Guangdong Pharmaceutical University — Guangzhou
• … and 17 more centers

Identifiers

NCT: NCT06157827 · LBL-024-CN002

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗