Total Neoadjuvant mFOLFOX6 Plus Suvemcitug and Enlonstobart With Selective Omission of Pelvic Radiotherapy for High-Risk Mid-Rectal Locally Advanced Rectal Cancer

This is a prospective, multicenter, open-label, single-arm Phase II study designed to evaluate the efficacy and safety of total neoadjuvant mFOLFOX6 combined with suvemcitug and enlonstobart in patients with MRI（Magnetic Resonance Imaging）-defined high-risk, mid-rectal, locally advanced rectal adenocarcinoma with pMMR/MSS status. All enrolled participants will receive 6 cycles of mFOLFOX6 plus suvemcitug and enlonstobart every 2 weeks. After 6 cycles, participants will undergo reassessment with pelvic MRI and systemic imaging. Participants who achieve at least 20% tumor regression on MRI without new high-risk radiologic features will continue with 2 additional cycles of mFOLFOX6 followed by radical total mesorectal excision surgery, without routine pelvic radiotherapy. Participants who do not meet the predefined regression threshold or show disease progression will receive long-course chemoradiotherapy with concurrent capecitabine, followed by 3 cycles of mFOLFOX6 and radical surgery.

Inclusion Criteria: 1. Age 18 to 75 years, male or female. 2. Histologically confirmed rectal adenocarcinoma. 3. pMMR or MSS status confirmed by genetic testing or immunohistochemistry. 4. Tumor lower margin located 5-12 cm from the anal verge, based on colonoscopy or MRI, consistent with mid-rectal cancer. 5. Pelvic MRI showing high-risk locally advanced rectal cancer, meeting at least one of the following criteria: cT3c/d, defined as tumor extension \>5 mm beyond the muscularis propria; cN2 disease, defined as \>=4 regional metastatic lymph nodes; definite extramural venous invasion positivity. 6. No distant metastasis confirmed by chest and abdominal imaging, including contrast-enhanced CT or MRI. 7. ECOG performance status of 0 or 1. 8. Adequate organ function, including absolute neutrophil count \>=1.5 x 10\^9/L; platelet count \>=100 x 10\^9/L; hemoglobin \>=9 g/dL; ALT and AST \90 mmHg. 14. NYHA class III-IV cardiac insufficiency or left ventricular ejection fraction \1+ at screening, or urine protein 1+ that does not return to normal on repeat testing within 24 hours. 16. Definite tendency for gastrointestinal bleeding, including active local ulcerative lesions with fecal occult blood positivity of ++; history of melena or hematemesis within 2 months; high risk of bleeding such as grade \>=3 bleeding within 6 months, hemoptysis \>=2.5 mL per episode, imaging evidence of tumor invasion into major blood vessels, or bleeding risk deemed unacceptable by the investigator. 17. High risk of gastrointestinal perforation or fistula, including gastrointestinal perforation or active peptic ulcer within 6 months, or pelvic tumor invasion of the bladder or rectum with potential fistula risk as judged by the investigator. 18. Coagulation abnormality, including INR \>1.5 or APTT \>1.5 x upper limit of normal, with bleeding tendency. 19. Chronic unhealed wound or fracture; major surgery within 4 weeks; or severe traumatic injury, fracture, or ulcer within 4 weeks. 20. Any condition that, in the investigator's judgment, makes the participant unsuitable for enrollment or unlikely to comply with follow-up.