A Phase 1/2 Study to Evaluate the Safety, Tolerability, and Efficacy of TROP2-Directed Antibody-Drug Conjugate LCB84, as a Single Agent and in Combination With an Anti-PD-1 Ab, in Patients With Advanced Solid Tumors

LigaChem Biosciences, Inc.8 个研究点分布在 2 个国家目标入组 300 人开始时间: 2023年10月5日最近更新: 2025年9月24日

适应症

干预措施

试验速览

阶段: 1 期
状态: 招募中
发起方: LigaChem Biosciences, Inc.
入组人数: 300
试验地点: 8
主要终点: Safety of LCB84 alone and LCB84 in combination with an anti-PD-1 Ab (Phase 1 and 2)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This is a first-in-human, Phase 1/2 study to evaluate LCB84, a TROP2-directed antibody-drug conjugate, alone and in combination with an anti-PD-1 Ab, in dose escalation (Phase 1) followed by dose expansion (Phase 2).

The study population in dose escalation (Phase 1) consists of patients with advanced solid tumors refractory to standard of care, or for whom no standard of care exists. After the MTD and/or RP2D for single agent LCB84 is determined, dose escalation cohorts with select tumor types will be enrolled. Combination LCB84 and anti-PD-1 Ab will be evaluated in dose escalation after a minimum of 2 dose levels of single agent LCB84 have established DLT safety, to determine the MTD and/or RP2D of combination LCB84 and anti-PD-1 Ab, and to continue into dose expansion cohorts in select tumor types.

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Parallel
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 —（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•Phase 1 Dose Escalation: histologically or cytologically confirmed advanced solid tumors refractory to standard of care treatment.
•Phase 2 Dose Expansion*: select histologically or cytologically confirmed advanced solid tumors refractory to standard of care treatment.
•*expansion cohort indications to be prioritized based on data from Phase 1 dose escalation.
•Prior treatment with TROP2-directed therapy is permitted.
•Measurable disease as defined by RECIST v1.1 or RANO-BM.
•Willingness to provide archival tumor tissue when available or to undergo pre-treatment biopsy if not available.
•Mandatory pre- and on-treatment biopsies for enrichment cohorts in Phase 1 dose escalation and Phase 2 expansion cohorts if deemed medically feasible and safe.
•Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
•Adequate organ function as defined by:
•Absolute neutrophil count (ANC) ≥1.5 x 109/L (1500/µL), without colony-stimulating factor support for the past 14 days
•Platelets ≥100.0 x 109/L (100 000/µL)
•Hemoglobin ≥9.0 g/dL
•Aspartate aminotransferase (AST) ≤2.5 x ULN; alanine aminotransferase (ALT) ≤2.5 x ULN (AST, ALT ≤5 x ULN if liver metastases present)

排除标准

•Active or progressing central nervous system (CNS) metastases or any evidence of leptomeningeal disease.
•Note: Patients with stable or treated CNS metastases may be eligible if all of the following criteria are met: 1) localized treatment for brain metastases completed at least 4 weeks prior to the first dose of study drug 2) no new or progressive neurologic symptoms and without need for immediate local therapy, steroids or anticonvulsants for symptom control (stable or decreasing steroid dose (a stable dose of ≤4 mg dexamethasone oral or equivalent) is permitted) 3) stable brain metastases for at least 1 month prior to screening (baseline) brain MRI.
•Persistent toxicities from previous systemic antineoplastic treatments >Grade 1, excluding alopecia and vitiligo.
•Systemic antineoplastic therapy (including antiestrogen therapy) within 5 half-lives or 4 weeks, whichever is shorter, prior to first dose of the study drug.
•Concomitant use of systemic steroids at dose of >10 mg of prednisone or its equivalent per day (exception for brain metastases, as described in exclusion criteria #1 above).

研究组 & 干预措施

LCB84 monotherapy

Experimental

IV infusion Q3W

干预措施: LCB84 (Drug)

LCB84 + anti-PD-1

Experimental

IV infusion Q3W

干预措施: LCB84 (Drug)

LCB84 + anti-PD-1

Experimental

IV infusion Q3W

干预措施: Anti-PD-1 monoclonal antibody (Drug)

结局指标

主要结局

Safety of LCB84 alone and LCB84 in combination with an anti-PD-1 Ab (Phase 1 and 2)

时间窗: Up to 48 months

Incidence and severity of AEs and SAEs

Overall Survival (Phase 2)

时间窗: Up to 24 months

Survival rates

Recommended Phase 2 Dose of LCB84 alone and LCB84 in combination with an anti-PD-1 Ab (Phase 1)

时间窗: Up to 24 months

Based on tolerability, preliminary anti tumor activity, and pharmacokinetics

Duration of Response (Phase 2)

时间窗: Up to 24 months