Neoadjuvant Radiotherapy Combined With NALIRIFOX and Adebrelimab in pMMR/MSS Locally Advanced Rectal Cancer: A Prospective, Randomized, Phase II Clinical Trial

Overview

To explore the efficacy and safety of radiotherapy combined with Adebrelimab and NALIRIFOX in patients with pMMR/MSS locally advanced rectal cancer

Interventions

• Combination product Adalimumab+NALIRIFOX→Short course radiotherapy →Adalimumab+NALIRIFOX
  Short course radiotherapy, 5 \* 5Gy, once a day, 5Gy each time, for 5 days; Adalimumab 1200 mg , D1, q2w, 2 cycles before radiotherapy and 6 cycles after radiotherapy; NALIRIFOX: Oxaliplatin 85 mg/m2, D1; Liposomal irinotecan 60 mg/m2, D1; LV 200 mg/m2; 5-FU 2400 mg/m2, Infusion for 48 hours; Repeat every 2 weeks. 2 cycles before radiotherapy and 6 cycles after radiotherapy;
• Combination product Adalimumab+NALIRIFOX→Long course chemoradiotherapy →Adalimumab+NALIRIFOX
  Long course chemoradiotherapy,50 Gy in 25 fractions, during the same period, capecitabine was 825 mg / m2, twice a day, 5 days a week; Adalimumab 1200 mg , D1, q2w, 2 cycles before radiotherapy and 6 cycles after radiotherapy; NALIRIFOX: Oxaliplatin 85 mg/m2, D1; Liposomal irinotecan 60 mg/m2, D1; LV 200 mg/m2; 5-FU 2400 mg/m2, Infusion for 48 hours; Repeat every 2 weeks. 2 cycles before radiotherapy and 6 cycles after radiotherapy;

Primary outcome measures

• CR rate [Time frame: up to 6 months]

Secondary outcome measures (6)

• Event-Free Survival(EFS) rate [Time frame: an expected average of 5 years]
• R0 resection rate [Time frame: an expected average of 2 years]
• ORR[Objective Response Rate] [Time frame: an expected average of 1.5 years]
• OPR [Time frame: an expected average of 1.5 years]
• Overall Survival [Time frame: an expected average of 5 years]
• Adverse events (AEs) [Time frame: an expected average of 1.5 years]

Eligibility criteria

Inclusion criteria

• Patients or their family members agree to participate in the study and sign the informed consent form;
• Age 18-75 years, male or female;
• Locally advanced rectal adenocarcinoma confirmed by histopathology;
• Clinical stage cT3-4bN0M0 or cTxN+M0, with or without MRF positive, with or without EMVI positive, expected to R0 resection;
• without intestinal obstruction;
• ECOG PS 0-1;
• expect survival up to 2 years;
• White blood cell count > 3.5×109/L；Platelet count ≥ 100×109/L；Hemoglobin ≥ 80 g/L；
• ALT ≤ 1.5×ULN, AST ≤ 1.5×ULN ；
• Serum creatinine ≤ 100μmol/l,

Exclusion criteria

• With inguinal lymph node metastasis or lateral lymph node metastasis (lymph node diameter ≥7 mm, or lymph node morphology and MRI features consistent with typical metastatic lymph nodes);
• Arrhythmia requiring antiarrhythmic treatment (except beta-blockers or digoxin), symptomatic coronary artery disease or myocardial ischemia (myocardial infarction within the last 6 months), or congestive heart failure exceeding NYHA Class II;
• Severe hypertension poorly controlled with medication;
• History of HIV infection, or active hepatitis B (HBV DNA ≥ 2000 IU/mL or 10⁴ copies/mL), or hepatitis C (positive hepatitis C antibody with HCV-RNA above the lower limit of detection of the assay);
• Active pulmonary tuberculosis (TB), currently receiving anti-tuberculosis treatment, or having received anti-tuberculosis treatment within 1 year prior to screening;
• Other active clinically severe infections (NCI-CTCAE Version 5.0);
• Preoperative evidence of distant metastasis outside the pelvis;
• Cachexia or organ function decompensation.
• History of pelvic or abdominal radiotherapy;
• Multiple primary colorectal cancers;
• Patients with seizures requiring treatment (e.g., corticosteroids or antiepileptic therapy);
• History of other malignancies within 5 years, except cured cervical carcinoma in situ or basal cell carcinoma of the skin;
• Drug abuse, or medical, psychological, or social conditions that may interfere with the patient's participation in the study or affect the evaluation of study results;
• Active autoimmune disease or history of autoimmune disease (including but not limited to: interstitial pneumonia, uveitis, enterocolitis, hepatitis, hypophysitis, nephritis, hyperthyroidism, and hypothyroidism);
• Receipt of any anti-infective vaccine (e.g., influenza vaccine, varicella vaccine, etc.) within 4 weeks prior to enrollment;
• Comorbidities requiring long-term treatment with immunosuppressive agents, or requiring systemic or local administration of corticosteroids at immunosuppressive doses (dose >10 mg/day of prednisone or other glucocorticoids with equivalent efficacy);
• Known or suspected hypersensitivity to the investigational drug, or to any medication administered in relation to this study;
• Any unstable condition that may jeopardize patient safety or compliance;
• Pregnant or lactating women, or women of childbearing potential not using adequate contraception;
• Refusal to sign the informed consent form.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, P. R. Chin — Guangzhou

Identifiers

NCT: NCT07622771 · B2026-229-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗