A Study to Evaluate Claudin 18.2-Directed ADC LCB02A in Advanced Solid Tumors

Официальное название

A First-in-Human Phase 1/2, Dose Escalation and Dose Expansion Study to Evaluate Safety, Tolerability, and Preliminary Efficacy of Claudin18.2 (CLDN18.2)-Directed Antibody-Drug Conjugate (ADC) LCB02A in Patients With CLDN18.2-positive Advanced Solid Tumors

Обзор

This is a Phase 1/2 open label study consisting of dose escalation cohorts (Phase 1) followed by expansion cohorts (Phase 2). The Phase 1 dose escalation population includes subjects with advanced solid tumors that are refractory to standard of care therapy or for whom no standard of care options are available. Once the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of single agent LCB02A is determined, the study will proceed to Phase 2 expansion cohorts in selected tumor types.

Вмешательства

• Препарат LCB02A
  CLDN18.2-directed human monoclonal antibody (Ab) linked to a topoisomerase I inhibiting payload.

Первичные конечные точки

• Safety of LCB02A (Phase 1 and 2) [Срок оценки: Up to 48 months]
• Recommended Phase 2 dose of LCB02A (Phase 1) [Срок оценки: Up to 24 months]
• Objective response rate (Phase 2) [Срок оценки: Up to 24 months]

Вторичные конечные точки (5)

• Plasma concentrations of LCB02A (Phase 1 and 2) [Срок оценки: Up to 48 months]
• Duration of Response (Phase 1 and 2) [Срок оценки: Up to 48 months]
• Disease control rate (Phase 1 and Phase 2) [Срок оценки: Up to 48 months]
• Progression Free Survival (Phase 1 and Phase 2) [Срок оценки: Up to 48 months]
• Overall Survival (Phase 1 and Phase 2) [Срок оценки: Up to 48 months]

Критерии участия

Критерии включения

• Phase 1 Dose Escalation: histologically or cytologically confirmed advanced solid tumors that are Claudin 18.2 positive and refractory to standard of care treatment.
• Phase 2 Dose Expansion: selected histologically or cytologically confirmed advanced solid tumors that are Claudin 18.2 positive and refractory to standard of care treatment. Expansion cohort indications will be prioritized based on data from the Phase 1 dose escalation portion.
• Prior treatment with Claudin 18.2 directed therapy is permitted.
• Measurable disease as defined by RECIST v1.1
• Willingness to provide archival tumor tissue when available, or to undergo a pre-treatment biopsy if archival tissue is not available.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ function as defined by:

• Absolute neutrophil count ≥ 1.5 × 109/L , without colony stimulating factor support for the past 14 days
• Platelet count ≥ 100 × 109/L
• Hemoglobin level ≥ 9.0 g/dL
• Total bilirubin ≤ 1.5× upper limit of normal (ULN) or <3 x ULN with Gilbert's syndrome or liver metastases at baseline
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5× ULN (≤ 5.0× ULN for subjects with liver metastases)
• Albumin ≥ 2.5 g/dL
• Creatinine clearance ≥ 60 mL/min

Критерии исключения

• Prior exposure to ADCs with a Topo1 inhibitor payload.
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.

Note: Patients may be considered for enrollment if they have previously treated brain metastases that are clinically stable or radiologically stable for at least 14 days prior to the first dose.

• Received radiotherapy within 21 days prior to the first dose of study drug. Note: For palliative radiotherapy for symptomatic improvement of non-central nervous system (CNS) lesions (total duration of radiotherapy ≤ 14 days), a radiation washout period of 7 days is required prior to the first dose.
• Any medical conditions that may confound the study results, interfere with the patient's compliance, or impair the interests of the subject, as assessed by the Investigator.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 4 центра

• Mass General Hospital — Boston
• START New York - Long Island — Lake Success
• Medical University of South Carolina — Charleston
• MD Anderson Cancer Center — Houston

South Korea · 3 центра

• Seoul National University Hospital — Seoul
• ASAN Medical Center — Seoul
• Samsung Medical Center — Seoul

Канада · 1 центр

• Princess Margaret Hospital — Toronto

Идентификаторы

NCT: NCT07460375 · LCB02A-1001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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