Tolecizumab Plus Chemoimmunotherapy for pMMR/MSS Locally Advanced Colon Adenocarcinoma

Официальное название

A Multicenter, Randomized, Open-Label, Blinded-Endpoint Phase II Study of Tolecizumab (a PCSK9 Inhibitor) Enhancing Chemoimmunotherapy as Neoadjuvant Treatment for Patients With pMMR/MSS Locally Advanced Colon Adenocarcinoma (TRIUNITE-08)

Обзор

This multicenter, randomized, open-label, blinded-endpoint Phase II trial assesses the efficacy and safety of tolecizumab (PCSK9 inhibitor) plus sintilimab/CapeOX chemoimmunotherapy as neoadjuvant treatment for pMMR/MSS locally advanced colon adenocarcinoma (cT3c+). 106 patients are 1:1 randomized to the combination or chemoimmunotherapy alone, with pCR as the primary endpoint.

Подробное описание

This is a multicenter, randomized, open-label, blinded-endpoint Phase II clinical trial designed to evaluate the efficacy and safety of tolecizumab (a PCSK9 inhibitor) combined with chemoimmunotherapy (sintilimab plus CapeOX regimen) as neoadjuvant treatment for patients with pMMR/MSS locally advanced colon adenocarcinoma (cT3c stage or above). A total of 106 eligible patients will be randomized 1:1 into two arms: Arm A (tolecizumab + sintilimab + CapeOX) and Arm B (sintilimab + CapeOX), both receiving 4 cycles of neoadjuvant therapy. The primary endpoint is the pathological complete response rate (pCR) after treatment; secondary endpoints include major pathological response rate (MPR), objective response rate (ORR), R0 resection rate, progression-free survival (PFS), overall survival (OS), and the incidence of adverse events (AEs) graded by NCI-CTCAE V5.0. A virtual historical control (single-agent CapeOX neoadjuvant chemotherapy) is set only for sample size calculation. The study will conduct safety follow-up for up to 90 days after the last administration and survival follow-up every 3 months for a total of 3 years, and also collect biological samples for exploratory biomarker analysis to explore the predictive factors of treatment efficacy. All study drugs and related examinations are provided free of charge for participants, and a Data and Safety Monitoring Board (DSMB) is established to monitor the study process and ensure participant safety.

Вмешательства

• Препарат Tolecizumab (PCSK9 Inhibitor)
  Tolecizumab (PCSK9 Inhibitor) 600mg, subcutaneous injection, Q6W (Weeks 1,7), 2 doses total Sintilimab (PD-1 Inhibitor) 200mg, intravenous infusion, Q3W (Weeks1,4,7,10), 4 cycles total CapeOX Regimen (Oxaliplatin + Capecitabine) Oxaliplatin 130mg/m² IV Q3W (4 cycles); Capecitabine 1000mg/m² oral twice daily, Days1-14 per cycle
• Препарат Sintilimab
  1. Oxaliplatin: 130mg/m² intravenous infusion, Q3W at Week 1,4,7,10, total 4 cycles; 2. Capecitabine: 1000mg/m² oral administration, twice daily, Days 1-14 of each chemotherapy cycle. All drugs free of charge. 2. Sintilimab 200mg intravenous infusion, administered every 3 weeks (Q3W) at Week 1, 4, 7, 10, total 4 cycles; provided free of charge by the sponsor, used for neoadjuvant immunotherapy.

Первичные конечные точки

• pCR [Срок оценки: The pCR rate will be evaluated after surgery, an average of 12 weeks]

Вторичные конечные точки (6)

• Disease-free survival [Срок оценки: 3 years]
• Overall survival (OS) [Срок оценки: 3 years]
• MPR [Срок оценки: From enrollment to 12 Weeks of treatment end]
• Curative resection [Срок оценки: Surgical operation assessment]
• Primary tumor downstaging rate [Срок оценки: From enrollment to 12 Weeks of treatment end]
• Objective Response Rate (ORR) [Срок оценки: After 4 cycles of neoadjuvant therapy (10 weeks)]

Критерии участия

Критерии включения

• Signed the written informed consent form and voluntarily participate in the study.

Pathohistologically confirmed colon adenocarcinoma with cT3c stage or above. Aged 18 to 80 years, regardless of gender. The lower edge of the tumor is more than 10 cm from the anus. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Sufficient bone marrow, liver, kidney and coagulation functions assessed by laboratory tests (in accordance with the local laboratory reference range).

No previous anti-tumor treatment for the current colon cancer (including radiotherapy, chemotherapy, surgery, etc.).

No pregnancy or lactation for female patients; male patients agree to take effective contraceptive measures during the study.

Критерии исключения

• Previous anti-tumor treatment for the current colon cancer. Previous use of PCSK9 inhibitors or PD-1/PD-L1 inhibitors. Active autoimmune diseases or a history of autoimmune diseases. Receiving immunosuppressant or systemic glucocorticoid therapy (except for local low-dose glucocorticoid use).

Active infection requiring systemic anti-infective treatment. Severe cardiovascular diseases (e.g., severe hypertension, myocardial infarction, heart failure, etc.).

Complicated primary tumor (e.g., tumor perforation, intestinal obstruction without relief after intervention).

Pregnant or lactating women. Other conditions that the investigator deems unfit for participation in the study (e.g., poor compliance, severe organ dysfunction, etc.).

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 · 1 центр

• Daping Hospital Third Military Medical University, chongqing, chongqing 400000 Recruiting — Чунцин

Идентификаторы

NCT: NCT07468630 · TRIUNITE-08

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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