Abstract 130P
Background
Neoadjuvant treatment of immune checkpoint inhibitors have shown a high pathologic complete response (pCR) rate in patients with dMMR/MSI-H, locally advanced colorectal cancer (LACRC). Cadonilimab (AK104), a novel bispecific antibody simultaneously targeting PD-1 and CTLA-4, was designed to boost anti-tumor activity with a favorable safety profile. Here, we primary reported the efficacy and safety of AK104 in the neoadjuvant treatment of dMMR/MSI-H LACRC, while concurrently exploring the potential for surgery avoidance.
Methods
The study was a multi-cohort, phase 2 trial, consisted of Cohort A (locally advanced colon cancer) and B (Locally Advanced Rectal Cancer). Patients (pts) with dMMR/MSI-H, LACRC were enrolled to receive AK104 (10mg/kg, iv, d1, q3w) for up to 8 cycles. The primary endpoint is the complete response rate (CR, pCR plus cCR). Secondary endpoints include MPR rate, R0 resection rate, DFS, OS, and safety.
Results
From April 2023 to August 2024, 34 pts were enrolled (26 in Cohort A and 8 in Cohort B). Baseline characteristics of pts are listed in the table. 34 pts had at least 2 cycles of treatment. In Cohort B, 4 pts completed the entire neoadjuvant treatment, and all reached the cCR. Currently, 13 pts (12 in Cohort A and 1 in Cohort B) received surgical resection, and the R0 resection rate was 100%. The pCR rate was 84.6% (11/13) and the MPR rate was 100 % (13/13). The median DFS was not reached. Treatment-related adverse events (TRAEs) occurred in 18/34(53%) pts. 5 /34 (14.7%) pts experienced grade 3-4 treatment-related adverse events (TRAEs), which included adrenocortical hypofunction (1 pt), myocarditis (1 pt), myositis (2 pts), and thrombocytopenia (1pt). No grade 5 AEs were observed. Table: 130P
| Characteristics | Cohort A, N=26 | Cohort B, N=8 |
| Age (years, median range) | 52 (18, 73) | 55 (48,68) |
| Gender | ||
| Female | 11 (42) | 1 (13) |
| Male | 15 (58) | 7 (87) |
| ECOG PS | ||
| 0 | 18 (69) | 6 (75) |
| 1 | 8 (31) | 2 (25) |
| Clinical T category | ||
| cT3 | 6 (23) | 5 (62) |
| cT4a | 20 (77) | 3 (38) |
| Clinical N category | ||
| N+ | 26 (100) | 7 (88) |
| N0 | 0 (0) | 1 (12) |
Conclusions
Cadonilimab showed promising efficacy with an outstanding pCR rate and manageable safety profile in locally advanced dMMR/MSI-H colorectal cancer patients. This trial is still ongoing and needs long-term follow-up.
Clinical trial identification
NCT05815290.
Legal entity responsible for the study
The authors.
Funding
Akeso Biopharma.
Disclosure
All authors have declared no conflicts of interest.
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