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).

LBA210 Background: Preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME) is recommended for mismatch repair-proficient (pMMR) or microsatellite stability(MSS) LARC. 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. This trial aims to investigate the efficacy and safety of SCRT followed by cadonilimab, a first-in-class anti-PD-1/CTLA-4 bispecific antibody, plus mFOLFOX6 in patients (pts) with LARC. Methods: Eligible pts aged 18-79 years with pMMR/MSS, nonmetastatic, stage cT3-4N0 or cT1-4N1-2 rectal adenocarcinoma located below the peritoneal reflection were enrolled and given SCRT (25Gy/5F) followed by 6 cycles of cadonilimab (6mg/kg, q2w) plus mFOLFOX6. The primary endpoint was pCR. Secondary endpoints included clinical complete response (cCR), major pathological response (MPR), disease-free survival (DFS), overall survival (OS), safety and quality of life. The exploratory endpoint explored potential biomarkers related to response. Results: From April 2023 to May 2024, 27 pts were enrolled and received at least 1 dose of treatment. As of data cutoff date of October 20, 2024,median follow-up was 9.7 months (IQR 5.4–18·8)，and all pts received study treatment, and 24/27(88.9%) underwent R0 resections (one delayed surgery due to chemotherapy-related pneumonia, while the other two were assessed unresectable). The primary endpoint was met with a pCR of 37%(10/27)(95% CI, 19.4%–57.6%) and MPR of 55.6%. A cCR of 22.2%(6/27) was observed, and among them, 83.3%(5/6) still received local excisions. The T downstaging was observed in 59.3%(16/27) while N downstaging in 66.7%(18/27). Grade 3–5 adverse events occurred in 5 (18.5%) of 27 pts; the most common were diarrhea (ten [37%]),nausea (ten [37%]) and fatigue (ten [37%]), and neutropenia (seven [26%]). Drug-related serious adverse events occurred in eight (30%) of 27 patients. No new safety signal was identified. Conclusions: In pts with pMMR/MSS LARC, neoadjuvant SCRT with cadonilimab plus mFOLFOX6 resulted in promising pCR rates with intolerable toxicities. Follow up continues. These data deserve further investigations in a phase III randomized trial. Clinical trial information: NCT05792735 .