Radiotherapy Plus CAPOX, and Iparomlimab and Tuvonralimab (QL1706) as Neoadjuvant Therapy for LARC

This study is a single-center, prospective, single-arm, open-label, Phase II clinical trial designed to evaluate the efficacy of radiotherapy combined with CAPOX, and Iparomlimab and Tuvonralimab (QL1706) as neoadjuvant therapy for locally advanced rectal cancer. Additionally, the study seeks to explore the relationship between biomarkers in blood and tumor tissue and treatment efficacy. Eligible participants (locally advanced rectal cancer) received pelvic radiotherapy (36 Gy/12 fractions; adaptive boost 6 Gy/2 fractions to GTVp/GTVn permitted) with one cycle of concurrent CAPOX during the first week (oxaliplatin 100 mg/m² IV D1; capecitabine 850 mg/m² PO bid). Two weeks after radiotherapy, four cycles of immunotherapy plus chemotherapy were given (iparomlimab and tuvonralimab 5 mg/kg IV D1; oxaliplatin 130 mg/m² IV D1; capecitabine 1000 mg/m² PO bid D1-14, Q3W). Two to three weeks after immunochemotherapy, surgery was performed (TME or intersphincteric resection with sphincter preservation (ISR) ), followed by adjuvant CAPOX. The primary endpoint was pathological complete response (pCR) rate.

Inclusion Criteria: * (1) The patient is histologically diagnosed with rectal adenocarcinoma. (2) Age ≥18 years, \ 1. Skin diseases that do not require systemic treatment (e.g., vitiligo, alopecia, psoriasis, or eczema) 2. Hypothyroidism caused by autoimmune thyroiditis that requires only stable doses of hormone replacement therapy 3. Type I diabetes that requires only stable doses of insulin replacement therapy 4. Childhood asthma that has completely resolved and requires no intervention in adulthood 5. The investigator determines that the disease will not recur without external triggering factors (9) Known or suspected active pulmonary tuberculosis (10) Subjects with active hepatitis B, inactive or asymptomatic hepatitis B virus (HBV) carriers (HBsAg positive) with HBV DNA \ 500 IU/mL or \ 2500 copies/mL), and subjects with active hepatitis C should be excluded. Inactive or asymptomatic carriers of hepatitis B who are treated and stable and meet the criteria of HBV DNA ≤500 IU/mL or ≤2500 copies/mL are eligible for enrollment. Subjects with cured hepatitis C who are HCVAb positive and HCV RNA negative are eligible for enrollment. (11) Subjects who require systemic treatment with glucocorticoids (\>10 mg/day prednisone or equivalent dose) or other immunosuppressive drugs within 14 days prior to randomization. The following are exceptions: a. Inhaled, ophthalmic, or topical corticosteroids are permitted if there is no active autoimmune disease. b. Corticosteroids are used as a pretreatment for infusion-related reactions or allergic reactions (e.g., medication before CT scans). (12) Pregnant or lactating women (13) Patients with currently uncontrolled comorbidities, such as decompensated cirrhosis, nephrotic syndrome, uncontrolled hyperglycemia, uncontrolled metabolic disorders, severe active peptic ulcer disease or gastritis, severe bleeding tendency, or coagulation disorders. (14) Patients with known allergies to any component of the study drug (oxaliplatin, capecitabine, QL1706); a history of severe allergic reactions to other monoclonal or bispecific antibodies; or known allergies to multiple substances or severe allergic diseases. (15) Patients who have received a live vaccine within 30 days prior to randomization or who plan to receive a live vaccine during the study period. (16) Patients with cognitive impairment or severe comorbid mental disorders, or those deemed by the investigator to have poor chemotherapy adherence; or other cases deemed unsuitable for participation in clinical trials by the investigator.