Short-Course Radiotherapy Followed by CAPOX With or Without Iparomlimab and Tuvonralimab in pMMR/MSS Locally Advanced Rectal Cancer

Официальное название

Short-Course Radiotherapy Followed by CAPOX With or Without Iparomlimab and Tuvonralimab in pMMR/MSS Locally Advanced Rectal Cancer (SCRIT): A Multicenter Phase III Randomized Controlled Trial

Обзор

This multicenter, randomized, controlled, phase III trial evaluates whether adding iparomlimab and tuvonralimab injection to CAPOX consolidation chemotherapy after short-course radiotherapy improves tumor response in patients with treatment-naive, proficient mismatch repair/microsatellite-stable (pMMR/MSS) locally advanced rectal adenocarcinoma. Eligible patients will be randomly assigned in a 1:1 ratio to receive short-course radiotherapy followed by CAPOX plus iparomlimab and tuvonralimab, or short-course radiotherapy followed by CAPOX alone. After total neoadjuvant therapy, patients with a clinical complete response may undergo a Watch-and-Wait strategy, whereas other patients will undergo total mesorectal excision according to standard clinical practice. The primary endpoint is complete response rate, defined as pathologic complete response after surgery or clinical complete response sustained for more than 1 year. Secondary endpoints include 3-year relapse-free survival, 3-year overall survival, sphincter preservation rate, and grade 3-4 acute adverse events. Exploratory analyses will assess tissue and blood biomarkers associated with treatment response.

Вмешательства

• Лучевая терапия Short-Course Radiotherapy
  Short-course external-beam radiotherapy will be delivered to the rectal primary tumor and corresponding lymphatic drainage regions using IMRT or VMAT. The prescribed dose is 25 Gy in 5 fractions over 1 week. No concurrent chemotherapy will be administered during short-course radiotherapy.
• Препарат Consolidation treatment (With ICIs)
  Iparomlimab and tuvonralimab injection will be administered at 5 mg/kg by intravenous infusion every 21 days for 6 cycles. CAPOX chemotherapy will consist of oxaliplatin 130 mg/m² intravenously on day 1 plus capecitabine 1000 mg/m² orally twice daily on days 1-14 of each 21-day cycle, for 6 cycles.
• Препарат Consolidation treatment (Without ICIs)
  CAPOX chemotherapy will consist of oxaliplatin 130 mg/m² intravenously on day 1 plus capecitabine 1000 mg/m² orally twice daily on days 1-14 of each 21-day cycle, for 6 cycles.

Первичные конечные точки

• Complete Response (CR) Rate [Срок оценки: From randomization to completion of definitive response assessment, including surgical pathological assessment after total neoadjuvant therapy or confirmation of sustained clinical complete response after at least 12 months of Watch-and-Wait follow-up]

Вторичные конечные точки (4)

• 3-Year Relapse-Free Survival (RFS) [Срок оценки: From randomization to the first documented disease relapse/recurrence, death from any cause, or 3 years after randomization, whichever occurs first.]
• 3-Year Overall Survival (OS) [Срок оценки: From randomization to death from any cause or 3 years after randomization, whichever occurs first.]
• Sphincter Preservation Rate [Срок оценки: From randomization to completion of definitive surgery, or to at least 12 months after initiation of Watch-and-Wait follow-up for patients who do not undergo surgery; approximately up to 18-24 months after randomization.]
• Incidence of Grade 3-4 Acute Adverse Events [Срок оценки: From the start of study treatment to 30 days after completion of neoadjuvant treatment.]

Критерии участия

Критерии включения

• Patients aged 18-75 years with histologically confirmed pMMR/MSS rectal adenocarcinoma are eligible if they have MRI-defined clinical stage II or III disease according to AJCC 8th edition, tumor located within 12 cm from the anal verge, and at least one high-risk feature, including cT4b, cN2, EMVI positivity, MRF positivity, lateral lymph node positivity, tumor deposits, or tumor located ≤5 cm from the anal verge. Patients must have no distant metastasis, ECOG performance status 0-1, life expectancy greater than 6 months, and adequate hematologic, hepatic, and renal function

Критерии исключения

• active or prior autoimmune disease requiring systemic treatment, use of immunosuppressive therapy or systemic corticosteroids at immunosuppressive doses, severe hypersensitivity to monoclonal antibodies, uncontrolled cardiac disease, significant coagulopathy or bleeding tendency, active infection, interstitial lung disease or severe pulmonary dysfunction, HIV infection or active hepatitis, prior or concurrent malignancy except specified cured cancers, recent investigational drug use, planned use of other systemic antitumor therapy during the study, pregnancy or breastfeeding, and any other condition judged by the investigator to make participation unsuitable.

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

• Shandong Cancer Hospital and Institute — Цзинань

Идентификаторы

NCT: NCT07686640 · SDZLEC2026-051-002

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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