Efficacy and safety of PD‐L1 blockade envafolimab as neoadjuvant treatment in mismatch repair‐deficient, locally advanced colorectal cancer: An open‐label, single‐arm study

Abstract Background Mismatch repair‐deficient (dMMR) colorectal cancer (CRC) is characterized by poor response to traditional chemotherapy but heightened sensitivity to immune checkpoint inhibitors (ICIs). However, it is unclear whether envafolimab, a subcutaneous programmed death‐ligand 1 inhibitor, provides comparable efficacy and safety as a neoadjuvant treatment in these patients compared to programmed cell death‐1 inhibitors. Methods This open‐label, single‐arm phase 2 trial enrolled patients with locally advanced dMMR CRC. Participants received subcutaneous envafolimab (300 mg every 3 weeks) for three to four cycles. Tumor response was assessed using computed tomography/magnetic resonance imaging and endoscopy, with pathological response evaluated postsurgery. The primary end point was the complete response rate (CR), including clinical complete response (cCR) and pathological complete response (pCR). The secondary end points included R0 resection rate, 3‐year disease‐free survival, 5‐year overall survival, and treatment‐related adverse events (AEs). Results Between August 22, 2022, to August 22, 2024, 15 patients were enrolled and received at least one dose of envafolimab. Two patients were excluded from efficacy analyses due to loss of follow‐up or patient refusal. Of the remaining 13 patients, seven (53.8%) achieved a complete response (two, cCR; five, pCR). The median time to CR was 3.1 months. Eleven patients underwent radical surgery, with no disease recurrence observed during follow‐up. Treatment‐related AEs were mild and of low incidence (28.6%), with only one patient experiencing a grade 3 fever. Subcutaneous administration of envafolimab demonstrated high patient convenience and satisfaction. Conclusions This preliminary study suggests that envafolimab is a promising effective and safe neoadjuvant option for locally advanced dMMR CRC; confirmation in larger cohorts is awaited.