A phase 2 trial, NeoCaCRT, presented at the 2025 Gastrointestinal Cancers Symposium, revealed that neoadjuvant short-course radiation therapy (SCRT) followed by cadonilimab and chemotherapy yielded promising pathological complete response (pCR) rates in patients with mismatch repair-proficient (pMMR) or microsatellite stable (MSS) locally advanced rectal cancer (LARC). The study suggests a potential new treatment approach for this patient population.
The open-label, single-arm trial enrolled 27 patients with stage II to III pMMR/MSS rectal adenocarcinoma. Patients received 5 Gy of SCRT in 5 fractions, followed by 6 mg/kg of cadonilimab every two weeks combined with mFOLFOX6 chemotherapy for six preoperative cycles. The primary endpoint was pCR, with secondary endpoints including clinical complete response (cCR), major pathological response (MPR), overall response rate, and safety.
Promising Response Rates
At the data cutoff on October 20, 2024, with a median follow-up of 9.7 months, the pCR rate was 37.0% (95% CI, 19.4%-57.6%). The clinical MPR rate was 55.6% (95% CI, 35.3%-74.5%), and the cCR rate was 22.2% (95% CI, 8.6%-42.2%). Among patients achieving cCR, 83.3% underwent local excisions. Wan He, a researcher at Shenzhen People’s Hospital and lead investigator, noted that radiological tumor shrinkage underestimated pathological regression.
Safety and Tolerability
The treatment regimen demonstrated a manageable safety profile. Treatment-related adverse events (TRAEs) of any grade occurred in 88.9% of patients, with grade 3/4 TRAEs observed in 22.2%. The most common TRAEs included diarrhea (37%), nausea (37%), and fatigue (37%). TRAEs led to treatment discontinuation in 18.5% of patients, and no treatment-related deaths were reported. Grade 3/4 TRAEs included diarrhea (14.8%) and neutropenia (3.7%).
Clinical Implications
"In patients with pMMR/MSS LARC, neoadjuvant SCRT with cadonilimab plus [chemotherapy] resulted in promising pCR rates with a manageable safety profile," stated Wan He. The findings suggest that this combination therapy could offer a valuable neoadjuvant option for patients with locally advanced rectal cancer. Further investigation in a phase 3 randomized trial is warranted to confirm these results and establish the efficacy of this treatment approach.
