131 Background: For patients with refractory metastatic colorectal cancer, current therapeutic options are with limited efficacy both rechallenge treatment and the immunotherapy. Both preclinical and clinical studies have shown that EGFR antibodies and immune checkpoint inhibitors have synergistic effects. This study investigates the clinical efficacy and safety of ICE regimen (Irinotecan Plus Cetuximab and Envafolimab. Envafolimab is a new PD-L1 agent and was used by subcutaneous injection). Methods: This is a retrospective observational and single-center study, conducted in Beijing Hospital involving patients with RAS/BRAF wild-type /MSS mCRC who had received at least two previous lines of treatment. Molecular status was reconfirmed via circulating tumor DNA (ctDNA) analysis. The primary endpoint was objective response rate (ORR) according to RECIST v1.1. The secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: Between July 2022 and August 2025, 20 patients received the ICE regimen: irinotecan (150 mg/m², Q2W), cetuximab (500 mg/m², Q2W), and envafolimab (200 mg, Q2W). The median age was 58.4 years (range: 40–74). Tumor locations included the left colon (n=11) and rectum (n=8)， only one right colon. Seventy percent of patients (14/20) had liver metastases and 40%（8/20）with both liver and lung metastases. The median number of prior therapies was 4.4 (range: 3–8). Among 19 evaluable patients, the ORR was 47.3% (9/19) and the DCR was 100% (19/19). At a median follow-up of 16.3 months, 85% (17/20) remained on treatment. Median PFS was 13.2 months (range: 2.1–31.3). Median OS was not reached due to limited events (3 deaths). Grade ≥3 treatment-related adverse events were mostly dermatologic, with rash occurring in 35% (7/20) of patients. Notably, one patient was treated with ICE as the third line regimen and achieved a clinical complete response (cCR) till now. Another patient experienced disease progression after a 1-year interruption of irinotecan, was re-challenged with ICE based on ctDNA confirmation of RAS/BRAF WT/MSS status, and he got SD. It is interesting that he had original FBXW7 mutation and resisted to prior three lines of systemic therapies before with short PFS. We also observed some patients had rechecked ctDNA after progressed and founded some new mutations. Conclusions: The ICE regimen demonstrates promising antitumor activity and manageable toxicity in heavily pretreated RAS/BRAF WT, MSS mCRC patients. A prospective, multicenter, open-label phase II trial (NCT06321081) investigating ICE as a rechallenge strategy is currently underway. Due to the favorable outcomes observed, we have initiated development of the “ICE2” protocol and are applying for its use as a first-line treatment in elderly patients with RAS/BRAF WT/MSS mCRC. Clinical trial information: NCT06321081 .
Huang et al. (Sat,) studied this question.