Cercek Andrea, Bachet Jean-Baptiste, Capdevila Jaume, Starling Naureen, Chen Eric, Salvatore Lisa, Bando Hideaki, O'Donnell Sean, Harfst Lauren, Szijgyarto Zsolt, Heinemann Volker
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
Sorbonne University, Department of Hepato-Gastroenterology and Digestive Oncology, Pitié Salpêtrière Hospital, Paris, France.
Clin Colorectal Cancer. 2025 Jun;24(2):325-330. doi: 10.1016/j.clcc.2025.02.003. Epub 2025 Feb 21.
Colorectal cancer (CRC) had the second highest cancer mortality worldwide in 2020; nearly a third of CRCs were rectal cancers (RC). A recent study demonstrated that dostarlimab, an immune-checkpoint inhibitor, was highly effective in treating mismatch repair deficient (dMMR) locally advanced RC as all included patients had a clinical complete response (cCR) without radiation or chemotherapy. This study's objective is to evaluate the efficacy and safety of dostarlimab monotherapy in patients with previously untreated locally advanced dMMR RC.
PATIENTS/METHODS: AZUR-1 (NCT05723562) is a multicenter, open-label, nonrandomized, single-arm phase 2 study enrolling approximately 150 patients across 10 countries. Key eligibility criteria include dMMR status or microsatellite instability-high (MSI-H) phenotype. Dostarlimab 500 mg will be administered intravenously every 3 weeks for 9 cycles. The primary endpoint is cCR by independent central review (ICR) at 12 months. Key secondary endpoints include cCR by ICR at 24 and 36 months, and 3-year event-free survival by investigator assessment. Additional secondary endpoints include organ preservation rate at 3 years and disease-specific survival and overall survival at 5 years. Efficacy and safety will be assessed in all patients who receive ≥1 dose of dostarlimab. All patients will be followed for 5 years (unless consent is withdrawn).
AZUR-1 will evaluate the efficacy of dostarlimab immunotherapy in dMMR/MSI-H RC. Utilizing novel aspects including long follow-up of all patients and standardization of clinical response assessment, this study will provide international multicentric data to evaluate tumor response in an immunotherapy setting and new evidence on long-term outcomes.
2020年，结直肠癌（CRC）的癌症死亡率在全球位列第二；近三分之一的结直肠癌为直肠癌（RC）。最近一项研究表明，免疫检查点抑制剂多斯塔利单抗在治疗错配修复缺陷（dMMR）的局部晚期直肠癌方面疗效显著，因为所有纳入研究的患者均实现了临床完全缓解（cCR），且无需放疗或化疗。本研究的目的是评估多斯塔利单抗单药治疗既往未治疗的局部晚期dMMR直肠癌患者的疗效和安全性。
患者/方法：AZUR-1（NCT05723562）是一项多中心、开放标签、非随机、单臂2期研究，在10个国家招募约150名患者。主要入选标准包括dMMR状态或微卫星高度不稳定（MSI-H）表型。多斯塔利单抗500 mg将每3周静脉注射一次，共9个周期。主要终点是独立中心审查（ICR）在12个月时的cCR。关键次要终点包括ICR在24个月和36个月时的cCR，以及研究者评估的3年无事件生存率。其他次要终点包括3年器官保留率、5年疾病特异性生存率和总生存率。将在所有接受≥1剂多斯塔利单抗的患者中评估疗效和安全性。所有患者将随访5年（除非撤回同意）。
AZUR-1将评估多斯塔利单抗免疫疗法在dMMR/MSI-H直肠癌中的疗效。本研究利用了包括对所有患者进行长期随访和临床反应评估标准化等新方法，将提供国际多中心数据以评估免疫治疗环境中的肿瘤反应，并提供长期结局的新证据。
