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

Korábbi kezelés

• Prior pelvic radiotherapy or prior systemic antitumor treatment for the current disease, including chemotherapy, targeted therapy, or immunotherapy.
• Active or previous severe autoimmune disease, including systemic lupus erythematosus or inflammatory bowel disease, or long-term use of systemic immunosuppressive agents.

Más betegség

• Imaging evidence of cT4 disease, mesorectal fascia positivity, or lateral lymph node metastasis.
• Known allergy or contraindication to any component of the study drugs, including oxaliplatin, 5-fluorouracil, suvemcitug, or enlonstobart.
• Serious cardiovascular events within 6 months, including acute myocardial infarction or stroke, refractory hypertension, or NYHA class III-IV heart failure.
• Active infection, including active tuberculosis, uncontrolled hepatitis B or C, or HIV infection with high viral load.
• Other malignancy within 5 years, except cured localized skin cancer or carcinoma in situ.
• Multiple primary colorectal cancers.
• Intestinal obstruction, intestinal perforation, or high risk of obstruction or perforation.
• Hypertension that cannot be controlled to the normal range with antihypertensive therapy, defined as systolic blood pressure >150 mmHg or diastolic blood pressure >90 mmHg.
• 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.
• 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.
• Chronic unhealed wound or fracture; major surgery within 4 weeks; or severe traumatic injury, fracture, or ulcer within 4 weeks.
• Any condition that, in the investigator's judgment, makes the participant unsuitable for enrollment or unlikely to comply with follow-up.

Laborértékek

• NYHA class III-IV cardiac insufficiency or left ventricular ejection fraction <50% on echocardiography.
• Coagulation abnormality, including INR >1.5 or APTT >1.5 x upper limit of normal, with bleeding tendency.

Egyéb

• Special histologic subtypes, including mucinous adenocarcinoma, signet-ring cell carcinoma, undifferentiated carcinoma, or other special histologic types.
• Pregnancy or breastfeeding.
• Inability to undergo MRI examination.
• Proteinuria, defined as urine protein >1+ at screening, or urine protein 1+ that does not return to normal on repeat testing within 24 hours.

• Age 18 to 75 years, male or female.
• Histologically confirmed rectal adenocarcinoma.
• pMMR or MSS status confirmed by genetic testing or immunohistochemistry.
• Tumor lower margin located 5-12 cm from the anal verge, based on colonoscopy or MRI, consistent with mid-rectal cancer.
• 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.
• No distant metastasis confirmed by chest and abdominal imaging, including contrast-enhanced CT or MRI.
• ECOG performance status of 0 or 1.
• 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 <=2.5 x upper limit of normal; total bilirubin <=1.5 x upper limit of normal; serum creatinine <=1.5 x upper limit of normal or creatinine clearance >=50 mL/min.
• Not pregnant or breastfeeding. Participants of reproductive potential must agree to use effective contraception during study treatment and for the protocol-specified period after the last dose.
• Voluntary participation with signed written informed consent.