A phase II study of short-course radiotherapy followed by sintilimab, anlotinib combined with CAPOX as neoadjuvant treatment for locally advanced MSS/pMMR rectal cancer (ZZU-1 study).

e15659 Background: Survival and organ function preservation are equally important for locally advanced rectal cancer. However, for microsatellite stable (MSS) or MMR-proficient (pMMR) tumors, the current neoadjuvant therapy modalities yield a limited pathological complete response (pCR) rate, typically not exceeding 30%. In this study, we aimed to investigate the efficacy and safety of neoadjuvant short-course radiotherapy followed by sintilimab, anlotinib combined with CAPOX for locally advanced MSS/dMMR rectal cancer. Methods: This single-arm, monocenter phase II study was conducted at the First Affiliated Hospital of Zhengzhou University. Patients with histologically confirmed T3-4N0M0 or T1-4N+M0 MSS/pMMR rectal cancer and the lower edge ≤10 cm from the anal verge were enrolled in this study. Patients first received short-course radiotherapy (5Gy×5) followed by systemic treatment one week later for a total of 6 cycles (sintilimab 200 mg infusion on d1, anlotinib 8mg orally once daily on days1-14 and CAPOX: oxaliplatin 130mg/m2 intravenously on d1, capecitabine 1000 mg/m2 orally twice daily on days 1-14, q21d). Surgery should be carried out 2 to 4 weeks after completing systemic therapy. For patients who have achieved cCR, a watch-and-wait strategy can be adopted. The primary endpoint was the pCR rate. Results: We planned to include 53 patients. At the data cutoff (Jan 20, 2025), 18 patients were enrolled in this study, 77.8% (14/18) were men.The median duration of follow-up was 10.2m (range, 0.5 to 28.5). The median distance from the anal verge was 3cm (range: 1 to 8.7cm). Fourteen cases (77.8%) were stage III tumors, stage cT4 accounted for 22.2% (4/18). 3 patients withdraw informed consent after completing less than four cycles of chemotherapy due to personal reasons. 4 patients were still under treatment. 11 patients reached the primary endpoint and underwent efficacy assessment. 3 patients underwent TME surgery (2 female patients underwent TME due to rectovaginal fistula), and all achieved pCR. 8 patients adopted a watch and wait strategy. Grade 3-4 treatment-related adverse events (TRAEs) occurred in 33.3% (6/18) of patients. liver damage (1/18, 5.6%), radiation enteritis (2/18,11.1%), thrombocytopenia (1/18, 5.6%), and rectovaginal fistula (2/18,11.1%). Conclusions: The preliminary data show the combination of short-course radiotherapy followed by sintilimab, and anlotinib combined with CAPOX was well tolerated and achieved nearly 100% CR that surpasses all reported data from existing studies. However, the efficacy and safety of this protocol need to be further studied. Clinical trial information: ChiCTR2100054135 .