China special issue on gastrointestinal tumors‐Cetuximab retreatment plus camrelizumab and liposomal irinotecan in patients with RAS wild‐type metastatic colorectal cancer: Cohort B of the phase II CRACK study

Patients with metastatic colorectal cancer (mCRC) have poor long‐term survival. Rechallenge with anti‐epidermal growth factor receptor (anti‐EGFR) based therapy has shown certain activity as late‐line therapy. To further improve clinical outcomes, we evaluated the antitumor efficacy and safety of cetuximab in combination with camrelizumab and liposomal irinotecan in patients with RASwt mCRC pretreated with anti‐EGFR‐based therapy. Patients with RASwt mCRC who had received at least two prior systemic therapies, including anti‐EGFR‐based treatment in the metastatic or unresectable disease setting, were enrolled in cohort B. Patients were treated with cetuximab (500 mg/m2) and camrelizumab (200 mg) plus liposomal irinotecan (HR070803, 60 mg/m2) intravenously once every 2 weeks. The primary endpoint was the objective response rate (ORR) by RECIST v1.1. The secondary endpoints included disease control rate (DCR), progression‐free survival (PFS), overall survival (OS) and safety. At the data cutoff (23 November 2022), 19 patients were enrolled in the two stages, and 16 were evaluable for efficacy analyses. The ORR was 25% (95% confidence interval [CI]: 10.2%‐49.5%), and DCR was 75% (95% CI: 50.5%‐89.8%). The median PFS and OS were 6.9 (95% CI: 2.6‐11.2) and 15.1 (95% CI: 6.1‐24.0) months, respectively. Grade 3 treatment‐related adverse events (TRAEs) occurred in 15.8% (3/19) of patients. No grade ≥4 TRAEs were found in the safety population. Our study suggests that anti‐EGFR retreatment therapy with cetuximab plus camrelizumab and liposomal irinotecan (HR070803) is a promising late‐line treatment option with good antitumor activity and well‐tolerated toxicity in RASwt mCRC patients. What's new? In recent years, anti‐EGFR‐based retreatment strategies have emerged as a valuable option for patients with metastatic colorectal cancer. In the current proof‐of‐concept phase II study, the novel anti‐EGFR retreatment strategy with cetuximab plus the PD‐1 inhibitor camrelizumab and liposomal irinotecan chemotherapy showed promising efficacy with durable benefits for patients with RASwt metastatic colorectal cancer in a late‐line setting. Adopting low‐dose liposomal irinotecan instead of irinotecan in triplet combinations led to low toxicity. Patients with a longer interval time or those receiving anti‐EGFR‐free intervening therapy after prior anti‐EGFR treatment may have better outcomes from the anti‐EGFR retreatment strategy.