165 - Short-Course Radiotherapy-Based Total Neoadjuvant Therapy with or without a PD-1 Inhibitor in pMMR Locally Advanced Rectal Cancer: Short-Term Results from a Randomized Phase 3 Trial (STELLAR II)
Presenter(s)
H. Li1, L. Wei2, W. Zhang3, N. Li3,4, W. Zhang5, Y. LU6, S. Qin7, Z. Lei8, X. Meng9, S. Liu10, G. Li11, Y. Wang12, W. Luo13, Y. Liu14, M. Meng15, H. Zhou16, J. Tang16, C. Hu17, Y. Tang1, and J. Jin3,5; 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, Xijing Hospital, Air Force Medical University, Xi'an, China, 3State 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, 4Department of Radiobiology, Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China, 5Department 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, 6Department of Radiation Oncology, Cancer Hospital of Henan Province, Zhengzhou, China, 7Department of Radiation Oncology, Peking University First Hospital, Beijing, China, 8Honghezhou Cancer Hospital, Gejiu, China, 9Anyang Tumor Hospital, Anyang, China, 10Department of Radiation Oncology, Jilin Provincial Cancer Hospital, Changchun, China, 11Department of Radiation Oncology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China, 12Department of Radiotherapy, Air Force Medical Center, Beijing, China, 13The First Affiliated Hospital of USTC,Division of Life Sciences and Medicine,University of Science and Technology of China, Anhui, China, 14Department of Radiation Oncology, Peking University Shenzhen Hospital, Shenzhen, China, 15Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Tianjin, China, 16Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 17Division of Biostatistics and Bioinformatics, Johns Hopkins School of Medicine, Baltimore, MD
Purpose/Objective(s): Total neoadjuvant therapy (TNT) is the standard of care for proficient mismatch repair (pMMR) locally advanced rectal cancer (LARC). While several phase II studies have suggested that adding immunotherapy to TNT can increase the complete response (CR) rate, phase 3 trials directly comparing TNT with versus without immunotherapy are lacking. The STELLAR II trial (NCT05484024) was therefore designed to conduct a head-to-head comparison, evaluating whether short-course radiotherapy (SCRT)-based TNT combined with a PD-1 inhibitor (iTNT) can safely improve the CR rate and survivals.
Materials/Methods: This was a multicenter, randomized, phase 2/3 trial involving patients with mid-to-low pMMR LARC. Eligible patients were randomly assigned to iTNT or TNT group. The iTNT group received SCRT (5 Gy x5) followed by 4 cycles of CAPOX and sintilimab. The TNT group received the same regimen without sintilimab. After neoadjuvant therapy, treatment strategy either resection or watch-and-wait (W&W) was determined based on evaluation, followed by 2 additional cycles of same prior regimen. Primary endpoints were the CR rate for phase 2 and 3-year DFS for phase 3. Interim phase II results were previously reported at ESTRO 2025; here, we present the short-term efficacy and safety data from the fully accrual of trial.
Results: From August 2022 to August 2025, 658 patients were screened and 588 were randomized, with 296 assigned to the iTNT group and 292 to the TNT group. Median age was 59 years, and 71.1% were male. Most patients had T3–4 (94.9%), node-positive (92.9%), and lower tumors (71.3%). 48.8% of patients had MRF+ disease and 45.4% had EMVI. All patients completed SCRT. Completion rates for 4-cycle of chemotherapy were 92.9% in the iTNT group and 94.1% in the TNT group. In the iTNT group, 254 patients (86.1%) received at least 4 cycles of sintilimab. Grade 3-4 toxicities occurred in 27.7% (iTNT) and 19.9% (TNT) of patients, and grade 3-5 immune-related adverse events occurred in 3.4% of patients. As of February 6, 2026, 458 patients had undergone surgery, with 8 awaiting surgery. Pathological complete response (pCR) was achieved in 41.7% (88/211) of the iTNT group versus 19.4% (48/247) of the TNT group. Ninety-two patients (15.6%) adopted a W&W strategy after clinical complete response (cCR). The overall CR rate was 51.9% (150/289) in the iTNT group, significantly higher than the 26.8% (78/291) in the TNT group (P <0.001). Short-term efficacy and survival outcomes continue to be followed.
Conclusion: This study provides the first substantial and reliable short-term efficacy and safety data for SCRT-based TNT combined with a PD-1 inhibitor in pMMR LARC. The significantly improved CR rate with iTNT offers a promising new option for organ preservation. Further 3-year survival outcomes are eagerly awaited.