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

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

Study Overview

• Status: Not yet recruiting
• Conditions: Rectal Cancers
• Intervention / Treatment: Combination product: Adalimumab+NALIRIFOX→Short course radiotherapy →Adalimumab+NALIRIFOX; Combination product: Adalimumab+NALIRIFOX→Long course chemoradiotherapy →Adalimumab+NALIRIFOX

• Study Type: Interventional
• Enrollment (Estimated): 84
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Chi Zhou; Phone Number: +86 20 87343920; Email: 447486353@qq.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, P. R. China

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

Exclusion Criteria:

1. 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);
2. 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;
3. Severe hypertension poorly controlled with medication;
4. 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);
5. Active pulmonary tuberculosis (TB), currently receiving anti-tuberculosis treatment, or having received anti-tuberculosis treatment within 1 year prior to screening;
6. Other active clinically severe infections (NCI-CTCAE Version 5.0);
7. Preoperative evidence of distant metastasis outside the pelvis;
8. Cachexia or organ function decompensation.
9. History of pelvic or abdominal radiotherapy;
10. Multiple primary colorectal cancers;
11. Patients with seizures requiring treatment (e.g., corticosteroids or antiepileptic therapy);
12. History of other malignancies within 5 years, except cured cervical carcinoma in situ or basal cell carcinoma of the skin;
13. 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;
14. Active autoimmune disease or history of autoimmune disease (including but not limited to: interstitial pneumonia, uveitis, enterocolitis, hepatitis, hypophysitis, nephritis, hyperthyroidism, and hypothyroidism);
15. Receipt of any anti-infective vaccine (e.g., influenza vaccine, varicella vaccine, etc.) within 4 weeks prior to enrollment;
16. 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);
17. Known or suspected hypersensitivity to the investigational drug, or to any medication administered in relation to this study;
18. Any unstable condition that may jeopardize patient safety or compliance;
19. Pregnant or lactating women, or women of childbearing potential not using adequate contraception;
20. Refusal to sign the informed consent form.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SCRT combined with Adalimumab and NALIRIFOX; Adalimumab combined with NALIRIFOX for two cycles. Radiotherapy: Short-course radiotherapy (SCRT) (25Gy/5F). Consolidation: Adalimumab combined with NALIRIFOX for six cycles	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;
Experimental: LCRT combined with Adalimumab and NALIRIFOX; Adalimumab combined with NALIRIFOX for two cycles. Radiotherapy: Long-course chemoradiotherapy (LCRT) (50Gy/25F, during the same period, capecitabine was 825 mg/m2, twice a day, 5 days a week). Consolidation: Adalimumab combined with NALIRIFOX for six cycles	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;

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CR rate	the number of patients with a pCR for those who underwent surgery and a cCR for those who underwent WW; The pCR was defined as the absence of any tumor cells from the primary tumor and lymph nodes in the specimen after radical surgery (ypT0N0) or the absence of any tumor cells in the lesion after local resection (ypT0).The cCR was defined as the absence of residual disease on DRE, MRI, and endoscopy.	up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	The time from the date of randomization to the death caused by any cause	an expected average of 5 years
R0 resection rate	The rate of negative margin microscopically	an expected average of 2 years
Event-Free Survival(EFS) rate	The percentage of patients without disease recurrence or progression or death due to any cause	an expected average of 5 years
ORR[Objective Response Rate]	Proportion of subjects in the analysis population who achieved complete response (CR) or partial response (PR) based on RECIST 1.1 criteria.	an expected average of 1.5 years
OPR	Organ Preservation Rate	an expected average of 1.5 years
Adverse events (AEs)	Adverse events and surgical safety	an expected average of 1.5 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 31, 2032

Study Registration Dates

• First Submitted: May 28, 2026
• First Submitted That Met QC Criteria: May 28, 2026
• First Posted (Actual): June 3, 2026

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: immunotherapy; radiotherapy; rectal cancer; neoadjuvant therapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Rectal Neoplasms
• Other Study ID Numbers: B2026-229-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: From Study complement
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No