Abstract 243P
Background
Cadonilimab (AK104), a novel bispecific antibody simultaneously targeting PD-1 and CTLA-4, was designed to boost anti-tumor activity. This study aimed to evaluate the efficacy and safety of oxaliplatin and capecitabine (XELOX) with or without AK104 in the neoadjuvant treatment for locally advanced mismatch repair-proficient (pMMR) rectal cancer (LARC) with uninvolved mesorectal fascia (MRF).
Methods
Patients (pts) with cT3-4a/N+, MRF- and pMMR LARC located at 5∼15 cm from the anal verge were randomized 1:1 to receive both 4 cycles of pre- and post-operative chemotherapy plus AK104 (Arm A) or XELOX alone (Arm B). The primary endpoint is pathological complete response (pCR) rate. Secondary endpoints include major pathological response (MPR) rate, R0 resection rate, DFS, OS, and safety.
Results
From April 2023 to March 2024, 46 pts were enrolled. A total of 31 pts (16 in arm A and 15 in arm B) who have completed at least 2 cycles of treatment were eligible for response assessment and included in this preliminary analysis. Baseline characteristics of patients are listed in the table. No patient got disease progression. At present, 25 pts (13 in arm A and 12 in arm B) underwent surgery and the R0 resection rate was 100%. The pCR rate was 15.4% (2/13) in arm A and 0% in arm B, and the MPR rate was 46.2% (6/13) in arm A and 8.3% (1/12) in arm B. The most common treatment-related adverse events (TRAEs, any grade) in AK104 group were elevated transaminase (50.0%), pyrexia (31.3%), and hyperthyroidism/hypothyroidism (18.8%). The most common grade 3-4 TRAEs was elevated transaminase (3 pts). No grade 5 AEs were observed. Table: 243P
Characteristic of patients
| Characteristics | Arm A, N=16 | Arm B, N=15 |
| Age (years, median range) | 62.5 (41, 74) | 50.5 (31,67) |
| Gender | ||
| Female | 5 (31) | 2 (13) |
| Male | 11 (69) | 13 (87) |
| ECOG PS | ||
| 0 | 11 (69) | 12 (80) |
| 1 | 5 (31) | 3 (20) |
| Clinical T category | ||
| cT3 | 11 (69) | 10 (67) |
| cT4a | 5 (31) | 5 (33) |
| Clinical N category | ||
| N+ | 15 (94) | 14 (93) |
| N0 | 1 (6) | 1 (7) |
| EMVI by MRI | ||
| Positive | 5 (31) | 8 (53) |
| Negative or uncertain | 11 (69) | 7 (47) |
Conclusions
Cadonilimab plus XELOX showed promising efficacy with encouraging pCR and MPR rate, and with manageable safety profile. This study is ongoing and related data will be reported in future.
Clinical trial identification
NCT05815303.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.