This phase 2/3 trial (NCT04856787) assessed the efficacy and safety of SHR-1701, a bifunctional protein targeting PD-L1 and TGF-β, in combination with BP102 (a bevacizumab biosimilar) and XELOX (capecitabine plus oxaliplatin) as a first-line treatment for unresectable metastatic colorectal cancer (mCRC). In this phase 2 study, a total of 62 patients with untreated, histologically confirmed colorectal adenocarcinoma and no prior systemic therapy for metastatic disease were enrolled. Patients received SHR-1701 (30 mg/kg), bevacizumab (7.5 mg/kg), and oxaliplatin (130 mg/m²) intravenously on day 1, along with oral capecitabine (1 g/m² twice daily) on days 1–14 of 21-day cycles. Up to eight induction cycles were administered, followed by maintenance therapy for responders or those with stable disease. The primary endpoints were safety and objective response rate (ORR) per RECIST v1.1. The combination achieved an ORR of 59.7% and a disease control rate (DCR) of 83.9%. Median progression-free survival (PFS) was 10.3 months (95% CI: 8.3–13.7), with 6- and 12-month PFS rates of 77.2% and 41.3%, respectively. The estimated 12-month overall survival (OS) rate was 67.7%. Grade ≥3 treatment-related adverse events (TRAEs) were reported in 59.7% of patients, with anemia and neutropenia (8.1% each) being the most common. Retrospective DNA sequencing revealed that high tumor mutational burden, neo-antigens, and SBS15 enrichment correlated with better responses. Elevated baseline lactate dehydrogenase was linked to shorter PFS. SHR-1701 combined with XELOX and bevacizumab demonstrated a manageable safety profile and potent antitumor activity in unresectable mCRC.

这项 2/3 期试验 （NCT04856787） 评估了 SHR-1701（一种靶向 PD-L1 和 TGF-β 的双功能蛋白）联合 BP102（一种贝伐珠单抗生物仿制药）和 XELOX（卡培他滨加奥沙利铂）作为不可切除的转移性结直肠癌 （mCRC） 一线治疗的疗效和安全性。在这项 2 期研究中，共有 62 名未经治疗、经组织学证实的结直肠腺癌患者入组，且既往未接受过转移性疾病的全身治疗。患者在第 1 天静脉注射 SHR-1701 （30 mg/kg）、贝伐珠单抗 （7.5 mg/kg） 和奥沙利铂 （130 mg/m²），并在 21 天周期的第 1-14 天口服卡培他滨（1 g/m² 每天两次）。最多进行 8 个诱导周期，然后对反应者或病情稳定的患者进行维持治疗。主要终点是符合 RECIST v1.1 的安全性和客观缓解率 （ORR）。该联合疗法的 ORR 为 59.7%，疾病控制率 （DCR） 为 83.9%。中位无进展生存期 （PFS） 为 10.3 个月 （95% CI： 8.3-13.7），6 个月和 12 个月 PFS 率分别为 77.2% 和 41.3%。估计 12 个月总生存率 （OS） 为 67.7%。59.7% 的患者报告了 ≥3 级治疗相关不良事件 （TRAE），其中贫血和中性粒细胞减少症 （各 8.1%） 是最常见的。回顾性 DNA 测序显示，高肿瘤突变负荷、新抗原和 SBS15 富集与更好的反应相关。基线乳酸脱氢酶升高与较短的 PFS 有关。SHR-1701 联合 XELOX 和贝伐珠单抗在不可切除的 mCRC 中显示出可控的安全性和有效的抗肿瘤活性。