A Study of CS23546 in Subjects With Advanced Tumors

Официальное название

A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of CS23546 in Subjects With Advanced Tumors

Обзор

The primary objectives of this study are to characterize the safety and tolerability of CS23546 and to evaluate the pharmacokinetic (PK) characteristics and recommended phase 2 dose (RP2D) of CS23546 in subjects with advanced tumors.

Подробное описание

This study is a single arm, open phase I trial, consisting of a dose escalation phase (single dose+multiple doses) and a dose expansion phase, accompanied by pharmacokinetic and pharmacokinetic studies. The first visit period (21 days) of single dose and multiple doses during the dose-increasing phase is the DLT observation period.

Вмешательства

• Препарат CS23546
  Tablets administered orally.

Первичные конечные точки

• Dose Limiting Toxicities (DLTs) [Срок оценки: Day 1 through Day 27]
• Maximum Tolerated Dose (MTD) [Срок оценки: Day 1 through Day 27]
• Time to Cmax (Tmax) [Срок оценки: up to Day 1 of cycle 5 (each cycle is 21 days)]
• Maximum plasma concentration (Cmax) [Срок оценки: up to Day 1 of cycle 5 (each cycle is 21 days)]
• Area Under the Curve (AUC) [Срок оценки: up to Day 1 of cycle 5 (each cycle is 21 days)]

Вторичные конечные точки (12)

• The inhibitory activity of Programmed cell death 1 ligand 1 (PD-L1) [Срок оценки: up to Day 1 of cycle 5 (each cycle is 21 days)]
• Interferon gamma (IFN-γ) [Срок оценки: up to Day 1 of cycle 5 (each cycle is 21 days)]
• Free PD-L1 [Срок оценки: up to Day 1 of cycle 5 (each cycle is 21 days)]
• C-X-C motif chemokine 9 (CXCL9) [Срок оценки: up to Day 1 of cycle 5 (each cycle is 21 days)]
• C-X-C motif chemokine 10 (CXCL10) [Срок оценки: up to Day 1 of cycle 5 (each cycle is 21 days)]
• Objective response rate (ORR) [Срок оценки: Until 28 days after the last dose of the study drug]
• Disease control rate (DCR) [Срок оценки: Until 28 days after the last dose of the study drug]
• Duration of response (DOR) [Срок оценки: Until 28 days after the last dose of the study drug]
• Time to progression (TTP) [Срок оценки: Until 28 days after the last dose of the study drug]
• time to progressive disease (TTR) [Срок оценки: Until 28 days after the last dose of the study drug]
• Progression free survival (PFS) [Срок оценки: Until 28 days after the last dose of the study drug]
• Overall survival (OS) [Срок оценки: Until 28 days after the last dose of the study drug]

Критерии участия

Критерии включения

• Male or female and ≥18 years of age on day of signing informed consent.
• Histologically or cytologically confirmed unresectable advanced recurrent/refractory solid tumor or lymphoma that is failure or or intolerant of all standard therapy or for which no standard therapy is available.
• Individuals are required to provide tumor tissue samples for prospective detection of Programmed cell death 1 ligand 1 (PD-L1) expression and/or Microsatellite instability (MSI) / the DNA mismatch repair (MMR) status. Subjects who cannot be provided during the dose escalation phase will be evaluated by the researchers and sponsors before deciding whether to enroll.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Adequate organ function.
• Life expectancy ≥12 weeks.
• Dose expansion phase: Cohort 1, Subjects with urothelial carcinoma. Cohort 2, Subjects with Extranodal NK/T-cell lymphoma (NKTCL). Cohort 3, Subjects with soft tissue sarcoma. Cohort 4, Subjects with PD-L1 expression positive and/or microsatellite-instability-high (MSI-H) / mismatch-repair-deficient (dMMR) advanced solid tumors or lymphoma

Критерии исключения

• Received anti-tumor therapy (including but not limited to chemotherapy, targeted therapy, anti angiogenic therapy, immunotherapy, cell therapy, radiotherapy, tumor embolization, etc.) or experimental drugs/devices that have not been approved for marketing within 28 days before the first medication.
• History of ≥ Grade 3 immune related Adverse Events (irAEs) or termination of treatment due to irAEs during prior treatment with Programmed death 1 (PD-1) /PD-L1 antibody.
• Active autoimmune diseases present during the screening period and systemic treatment was received within 2 years before the first medication. Individuals who only require hormone replacement therapy (such as thyroxine, insulin, or physiological corticosteroids used for adrenal or pituitary insufficiency) can be enrolled.
• Presence of central nervous system metastasis and/or meningeal metastasis.
• Dose expansion phase: Subjects with solid tumors or lymphoma who have previously received PD-L1 inhibitors and belong to primary resistance.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Sun Yat-sen University Cancer Cancer — Гуанчжоу

Идентификаторы

NCT: NCT06245122 · CS23546-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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