SKB500 Combinations in Patients With Esophageal Squamous Cell Carcinoma

Официальное название

A Phase II, Multicenter, Open-Label Study to Evaluate the Safety and Efficacy of SKB500 Combinations in Patients With Esophageal Squamous Cell Carcinoma

Обзор

The purpose of this study is to evaluate the safety, tolerability and preliminary antitumor activity of SKB500 combinations in patients with Esophageal Squamous Cell Carcinoma. The study is divided into three parts: the safety run-in phase, randomized enrollment phase and cohort expansion phase.

Подробное описание

This is a Phase II, multicenter, open-label study to evaluate the safety, tolerability and preliminary antitumor activity of SKB500 combinations in patients with Esophageal Squamous Cell Carcinoma. The study is divided into three parts: the safety run-in phase, randomized enrollment phase and cohort expansion phase.

Вмешательства

• Препарат SKB500
  SKB500 will be administered as an intravenous infusion(IV), every 3 weeks on Day 1 of each 21-day cycle.
• Препарат Tislelizumab
  Tislelizumab will be administered as an intravenous infusion(IV) every 3 weeks on Day 1 of each 21-day cycle .
• Препарат Cisplatin
  Cisplatin will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle.
• Препарат 5 - FU
  5-FU will be administered as an intravenous infusion(IV) every 3 weeks on Day 1-5 of each 21-day cycle.

Первичные конечные точки

• Objective Response Rate (ORR) [Срок оценки: up to 24 months]
• Incidence and severity of adverse events (AEs) and serious adverse event(SAEs) [Срок оценки: up to 24 months]

Вторичные конечные точки (7)

• Progression-free survival (PFS) [Срок оценки: up to 24 months]
• Duration of response (DOR) [Срок оценки: up to 24 months]
• Disease control rate (DCR) [Срок оценки: up to 24 months]
• Overall Survival (OS) [Срок оценки: up to 24 months]
• Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of SKB500-ADC, SKB500-TAB and free payload [Срок оценки: up to 24 months]
• Pharmacokinetic Parameter Minimum Plasma Concentration (Cmin) of SKB500-ADC, SKB500-TAB and free payload [Срок оценки: up to 24 months]
• Anti-drug Antibodies (ADA) for SKB500 [Срок оценки: up to 24 months]

Критерии участия

Критерии включения

• Age ≥18 years and ≤75 years
• Histologically or cytologically confirmed unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC), who are ineligible for curative-intent therapies:

• Safety run-in phase (Cohort 1, 2 and 3): received no more than 1 prior line of systemic therapy for locally advanced or metastatic ESCC.
• Safety run-in phase (Cohort 4), randomized enrollment phase and cohort expansion phase: no prior systemic therapy for locally advanced or metastatic ESCC.
• Participants are required to provide tumor tissue samples for biomarker analysis.
• Has at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy ≥ 12 weeks.

Критерии исключения

• Histology or cytology confirms the presence of concurrent adenocarcinoma components.
• Leptomeningeal, brainstem, spinal, spinal cord compression, or active CNS metastases.
• Risk of esophagotracheal/esophagopleural fistula, or symptomatic invasion/compression of vital organs/major blood vessels.
• Active autoimmune disease requiring systemic therapy within past 2 years.
• Weight loss ≥10% within 4 weeks prior to the first dose, or Nutritional Risk Index (NRI) < 83.5.
• Severe infection within 4 weeks or active infection requiring systemic treatment within 2 weeks pre-dose.
• Uncontrolled comorbidities (e.g., decompensated liver cirrhosis, nephrotic syndrome, uncontrolled metabolic disorders, Grade ≥2 peripheral neuropathy).
• Cardiovascular/cerebrovascular events within 6 months pre-dose (e.g., Myocardial Infarction, unstable angina, acute/persistent ischemia, Grade 3/4 Heart Failure, symptomatic/uncontrolled arrhythmia, Cerebrovascular Accident, Transient Ischemic Attack).
• Uncontrolled hypertension, diabetes, or recurrent pleural/pericardial/abdominal effusion requiring drainage.
• History of interstitial lung disease (ILD) or noninfectious pneumonitis that require steroid treatment, or currently has ILD/noninfectious pneumonitis.
• Unresolved to grade ≤ 1 of prior anti-cancer treatment toxicities criteria per CTCAE v6.0.
• Previously received B7-H3-targeted agents, including antibody, antibodydrug conjugate (ADC), and other agents.
• Previously received treatment with an ADC that consists of a topoisomerase l inhibitor.
• Pregnant or lactating women.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 23 центра

• Jilin Cancer Hospital — Changchun
• Chengdu Fifth People's Hospital — Чэнду
• Sichuan Cancer Hospital & Institute — Чэнду
• West China Hospital, Sichuan University — Чэнду
• Chongqing University Three Gorges Hospital — Чунцин
• Fujian Cancer Hospital — Фучжоу
• Harbin Medical University Cancer Hospital — Ha’erbin
• Cancer Hospital of Shandong First Medical University — Цзинань
• … и ещё 15 центров

Идентификаторы

NCT: NCT07700667 · SKB500-Ⅱ-04

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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