According to results from the phase 2 NeoCaCRT trial, neoadjuvant short-course radiation (SCRT) plus cadonilimab, a first-in-class anti-PD-1/CTLA-4 bispecific antibody, and mFOLFOX6 demonstrated promising response among patients with locally advanced mismatch repair-proficient (pMMR) or microsatellite stability (MSS) rectal cancer. 

These results were presented by Wan He, MD, PhD, Shenzhen People’s Hospital, Shenzen, China, at the 2025 ASCO Gastrointestinal Cancers Symposium in San Francisco, California.  

“Preoperative chemoradiotherapy (CRT) followed by total mesorectal excision is recommended for [patients with pMMR or MSS locally advanced rectal cancer],” stated Dr He and coauthors. “Recent studies have shown that anti-PD-1/PD-L1 in combination with CRT can improve pathological complete response (pCR) compared to CRT in the neoadjuvant setting.” 

In this study, 27 patients with locally advanced, non-metastatic stage cT3-4N0 or cT1-4N1-2 pMRR or MSS rectal adenocarcinoma were assigned to receive SCRT (25 Gy in 5 fractions) followed by 6 cycles of cadonilimab (6 mg/kg administered once every 2 weeks) and mFOLFOX6. The primary end point was pCR rate. Key secondary end points included clinical complete response (cCR) rate, major pathological response (MPR) rate, and safety. 

At a median follow-up of 9.7 months, the pCR rate was 37%. The cCR rate was 22.2% and the MPR rate was 55.6%. Among patients who experienced cCR, 83.3% received local excisions. T-downstaging was observed in 59.3% of patients and N-downstaging was observed in 66.7% of patients. Grade 3 to 5 adverse events occurred in 18.5% of patients. The most common events included diarrhea (37%), nausea (37%), fatigue (37%), and neutropenia (26%). Drug-related serious adverse events occurred in 30% of patients. There were 5 patients who discontinued treatment due to treatment-related adverse events, and no treatment-related deaths. No new safety signals were identified. 

Results demonstrate that “neoadjuvant SCRT with cadonilimab plus mFOLFOX6 resulted in promising pCR rates with manageable safety profile,” concluded Dr He et al. “These data deserve further investigations in a phase III randomized trial.” 

Source: 

He W, Huang J, Liao G, et al. Short-course radiation (SCRT) followed by 6 cycles of cadonilimab plus mFOLFOX6 as neoadjuvant therapy for patients with locally advanced rectal cancer (LARC): A multicenter, single arm, phase II trial (NeoCaCRT). Presented at The 2025 ASCO Gastrointestinal Cancers Symposium. January 23-25, 2025. Abstract LBA 210