KC1036 in Combination With PD-1 Antibody and Platinum-based Chemotherapy for First-line Advanced Esophageal Cancer

Официальное название

A Phase II Clinical Study to Evaluate the Efficacy and Safety of KC1036 Combined With PD-1 Antibody and Platinum-based Chemotherapy as First-line Treatment for Advanced Recurrent or Metastatic Esophageal Squamous Cell Carcinoma

Обзор

The purpose of this study is to evaluate the efficacy and safety of KC1036 in combination with PD-1 antibody and platinum-based chemotherapy as a first-line treatment for patients with unresectable locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC).

Подробное описание

This multicenter Phase II study evaluates KC1036 in combination with PD-1 antibody and platinum-based chemotherapy as first-line treatment for advanced esophageal squamous cell carcinoma. The trial comprises a Phase IIa dose-escalation and expansion phase to assess the safety of KC1036 at 20, 30, or 40 mg QD, followed by a Phase IIb randomized evaluation of 2-3 cohorts (up to 50 subjects per arm) to identify the recommended Phase III dose. Subjects receive daily oral KC1036 plus toripalimab, paclitaxel, and cisplatin every 3 weeks until confirmed disease progression assessed by the RECIST V1.1 standard, death, intolerable toxicity, initiation of a new anti-tumor therapy, other reasons leading to treatment discontinuation as specified by protocol.

Вмешательства

• Препарат KC1036
  Dosage: 20 mg, 30 mg, or 40 mg; Route: Oral; Frequency: Once daily (QD) under fasting conditions (at least 2 hours before and 1 hour after dosing), 21 days as a cycle.
• Препарат Toripalimab
  Dosage: 240 mg; Route: Intravenous (IV) infusion; Frequency: Every 3 weeks (Q3W) on Day 1 of each 21-day cycle, for up to 2 years.
• Препарат Paclitaxel
  Dosage: 175 mg/m2; Route: IV infusion; Frequency: Day 1 of each 21-day cycle, for a maximum of 6 cycles.
• Препарат Cisplatin
  Dosage: 60-75 mg/m2; Route: IV infusion; Frequency: Day 1 of each 21-day cycle, for a maximum of 6 cycles.
• Препарат KC1036
  Dosage: Selected doses from Phase IIa (20 mg, 30 mg, or 40 mg); Route: Oral; Frequency: Once daily (QD) under fasting conditions, 21 days as a cycle.

Первичные конечные точки

• Objective Response Rate (ORR) [Срок оценки: Baseline to study completion (approximately 24 months)]

Вторичные конечные точки (5)

• Progression-free survival (PFS) [Срок оценки: Baseline to study completion (approximately 24 months)]
• Disease Control Rate (DCR) [Срок оценки: Baseline to study completion (approximately 24 months)]
• Duration of Response (DOR) [Срок оценки: Baseline to study completion (approximately 24 months).]
• TTR [Срок оценки: Baseline to study completion (approximately 24 months)]
• Adverse events (AEs) [Срок оценки: Baseline to 30 days after the last dose of study treatment]

Критерии участия

Критерии включения

• Males or females aged 18 to 75 years;
• Histologically or cytologically confirmed esophageal or esophageal-gastric junction squamous cell carcinoma;
• Patients who have not received prior systemic anti-tumor therapy for the current recurrent or metastatic disease;
• At least one measurable tumor lesion according to RECIST 1.1;
• Eastern Cooperative Oncology Group performance status score of 0 or 1;
• Life expectancy > 12 weeks;
• BMI≥16.0 kg/m2;
• Adequate bone marrow, renal, and hepatic function;
• Female patients of childbearing potential with a negative blood pregnancy test completed within 7 days before the first dose;
• Patients should participate in the study voluntarily and sign informed consent.

Критерии исключения

• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastasis;
• Other malignancies within the past 5 years;
• Known hypersensitivity to any monoclonal antibodies or chemotherapy components;
• Gastrointestinal abnormalities;
• High risk of bleeding or fistula due to tumor invasion of adjacent organs, or existing esophageal/tracheal fistula;
• Cardiovascular and cerebrovascular diseases;
• Prior therapy with anti-angiogenic drugs or immunotherapy; Systemic therapy, investigational drugs, or live vaccines within 4 weeks prior to the first dose; Palliative radiotherapy within 2 weeks or major surgery within 28 days prior to enrollment;
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage;
• Presence of unresolved toxicities from prior anti-tumor therapy, defined as having not resolved to NCI CTCAE 5.0 Grade 0 or 1;
• Active autoimmune disease or a history of autoimmune disease requiring systemic treatment;
• Active infections, including severe infection (CTCAE > Grade 2) within 4 weeks, active tuberculosis, or positive status for HIV, HBV, or HCV;
• Pregnant or lactating women;
• Female subjects of child-bearing potential and male subjects of reproductive capacity who do not agree to use contraceptive measures during the study and for 6 months after the end of the study;
• Other conditions assessed by the investigator that would increase safety risks or interfere with the study results.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Cancer Hospital, Chinese Academy of Medical Sciences — Пекин

Идентификаторы

NCT: NCT07481058 · KC1036-COM-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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