112 - Efficacy and Safety of Short-Course Radiotherapy followed by Sequential Chemotherapy and AK104 in Locally Advanced Rectal Cancer: Results from a Prospective, Multicenter Phase II Trial
Presenter(s)
T. Xu1, L. Feng2, Y. Tang3, D. Li4, W. Zhang2, H. Li1, H. Ma1, H. Zhou5, W. Kang6, W. Huang7, S. Zou8, Y. Chi9, Y. Wang10, F. Deng2, L. Jiang11, C. Hu12, Y. Chen13, and J. Jin1,14; 1State Key Laboratory of Molecular Oncology and Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China, 2Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China, 3Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China, 4Laboratory Animal Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, Beijing, China, 5State Key Laboratory of Molecular Oncology and Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (PUMC), Beijing, China, 6Department of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China, 7Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China, 8National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China, 9State Key Laboratory of Molecular Oncology and Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 10Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China, 11Department of Image,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 12Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 13Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China, 14State Key Laboratory of Molecular Oncology and Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Purpose/Objective(s):
The integration of monoclonal antibody immunotherapy with chemotherapy following short-course radiotherapy (SCRT) has demonstrated improved complete response (CR) rates in locally advanced rectal cancer (LARC). AK104, a bispecific antibody simultaneously targeting PD-1 and CTLA-4, aimed to enhance anti-tumor activity with manageable safety. This trial evaluates the efficacy and safety of adding AK104 to SCRT based total neoadjuvant therapy (biTNT) for LARC.Materials/Methods:
This is a single-arm, multi-center, prospective, phase II trial for cT3-T4N0 or cT2-4N+ rectal cancer (NCT05794750). Patients received neoadjuvant SCRT (25Gy/5Fx), followed by 4 cycles of CAPOX combined with AK104 (10mg/kg, d1, q3w). Total mesorectal excision (TME) is performed 4 weeks after neoadjuvant treatment, followed by 2 cycles of adjuvant CAPOX. A watch-and-wait (W&W) approach is considered for patients achieving clinical CR (cCR). The primary endpoint is the CR rate (pathological complete response [pCR] plus cCR), with a hypothesized CR rate of 40% after biTNT, compared to a historical rate of 21.8% with conventional TNT.Results:
A total of 52 patients were enrolled, with a median age of 61 years (range: 34-74). All patients had MSS/pMMR type cancer. Of these, 34 (65.4%) were male. Tumor characteristics included 49 patients (94.2%) with tumors located in the distal or middle third of the rectum, 50 (96.2%) with cT3 or T4 lesions, and 36 (69.2%) with cN2 stage. Additionally, 29 patients (55.8%) had mesorectal fascia (MRF) involvement, and 30 (57.7%) had extramural vascular invasion (EMVI). As of February 8, 2025, all patients completed SCRT without dose reduction. 49 patients completed radiological assessments after neoadjuvant treatment. Among them, the completion and full-dose completion rates of neoadjuvant AK104 with chemotherapy were 82.7% and 71.4%, respectively. 44 (89.8%) completed four cycles of cadonolimab at full-dose. Nine achieved a cCR and have maintained W&W strategy without regrowth; 31 underwent TME with a 100% R0 resection rate; and 3 opted for local excision. Additionally, two patients who did not achieve cCR declined surgery, while four patients remain on the surgical waiting list. The pCR and CR rates were 35.3% (12/34) and 46.6% (21/45) based on the available data. No grade 5 AEs were noted. Detailed AE data are presented in Table 1. Final statistical analysis of the CR and AEs rates will be completed within the next 3 months.Conclusion:
BiTNT achieved a favorable CR rate with acceptable tolerance in patients with LARC, and thus has the potential to offer new options for organ preservation. Abstract 112 - Table 1: Grade 3 to 4 acute adverse event during preoperative treatment| Grade 3 to 4 acute adverse event | Evaluable patients (N=49 [%]) |
| Hematological | 17 (34.7) |
| Thrombocytopenia | 12 (24.5) |
| Leukopenia | 7 (14.3) |
| Hepatic dysfunction | 1 (2.0) |
| Non-hematological | 3 (5.8) |
| Hand-foot syndrome | 2 (3.8) |
| Diarrhea | 1 (2.0) |
| Immune-related | 4 (7.8) |
| Myositis | 2 (3.8) |
| Myocarditis | 1 (2.0) |
| Dermatitis | 1 (2.0) |