Abstract 249P
Background
Recent studies have suggested promising complete response rate when combining single-agent immunotherapy plus chemotherapy with short-course radiotherapy (SCRT) in locally advanced rectal cancer (LARC). Cadonilimab (AK104), a novel bispecific antibody simultaneously targeting PD-1 and CTLA-4, is designed to boost anti-tumor activity with improved safety profile. This trial aimed to evaluate the efficacy and safety of preoperative SCRT combined with subsequent CAPOX (capecitabine and oxaliplatin) and cadonilimab in patients with LARC.
Methods
This is a single-arm, multi-center, prospective, phase II study for cT3-T4N0 or cT2-4N+ rectal cancer.Patients received SCRT (25Gy/5Fx) with subsequent 4 cycles of CAPOX plus AK104 (10mg/kg iv, d1, q3w), followed by total mesorectal excision (TME) after 4 weeks, and adjuvant treatment with CAPOX (2 cycles), while a watch and wait (W&W) option can be applied to patients achieving cCR. The primary endpoint is the complete response rate (CR, pathological complete response [pCR] plus cCR ).The secondary endpoints include 3-year DFS, safety, etc.
Results
Up to 2 April 2024, 22 patients were enrolled with a median age of 56 years. 100% patients had MSS/pMMR type cancer, with 20 patients (91%) at stage III. All of them showed one of the following features: lower location (≤5cm), cT4, cN2, MRF+ and EMVI+. 9 patients have already completed the radiological assessment after receiving neoadjuvant treatment. 3 out of the 9 patients achieved cCR and adopted W&W, 6 patients underwent TME,with R0 resection rate of 100% and the pCR rate was 33.3%(2/6). The CR rate was 55.6% (5/9). 5 (22.7%) patients experienced grade 3-4 TRAEs, including thrombocytopeni, rash, leukopenia. Immune-related AEs were observed in 3 patients (13.6%), only one patient experience grade 3 irAE, which was immune-related dermatitis. No serious AEs or grade 5 AEs were noted.
Conclusions
Neoadjuvant SCRT followed by CAPOX plus cadonilimab has achieved a favorable CR rate with good tolerance in patients with LARC, and thus has the potential to offer new options for organ preservation.
Clinical trial identification
NCT05794750.
Legal entity responsible for the study
The authors.
Funding
Akeso Biopharma.
Disclosure
All authors have declared no conflicts of interest.