SCRT VS LCRT Followed by PD-L1 Inhibitor Plus CAPEOX as TNT in Patients With LARC

NCT07284992 | Recruiting Phase 2

• 1 other identifier: SPRING03
• Study Type: interventional
• Target: 208
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, cohort, prospective study to evaluate the efficacy and safety of Adebrelimab combined with radiotherapy and chemotherapy as preoperative neoadjuvant therapy for patients with locally advanced rectal cancer. In the study, all subjects who meet the inclusion criteria will enter the short-term radiotherapy queue and the long-term radiotherapy queue at the ratio of 1:1. The short-term radiotherapy queue plans to receive Adebrelimab combined with short-term radiotherapy (5\*5Gy) and Capox chemotherapy as neoadjuvant therapy. The long-term radiotherapy queue plans to receive Adebrelimab combined with long-term radiotherapy (1.8gy × 25-28 times) and capox chemotherapy as neoadjuvant therapy. The TME surgery will be performed 2-3 weeks after the last neoadjuvant therapy is completed. If the surgery cannot be performed within the time window specified in the plan (such as delayed adverse reactions, etc.), the researcher will conduct the surgery according to the patients' requirements.The actual clinical conditions of the subjects were comprehensively considered.

Conditions

Rectal Cancer; Radiotherapy; Advanced Stage Colorectal Cancer

Keywords

Immune checkpoint inhibitors; Adebrelimab Injection

Outcome Measures

Primary Outcomes (1)

• CR rate

  pathological complete remission rate (PCR) and clinical complete remission rate (CCR)

  From enrollment to the end of surgery,assessed up to 6 months

Secondary Outcomes (6)

• partial remission rate (PR)

  The evaluation time from enrollment to the first efficacy evaluation is up to 3 months

• Objective response rate (ORR)

  The evaluation time from enrollment to the first efficacy evaluation is up to 3 months

• Major Pathological Response Rate (MPR)

  From enrollment to the end of surgery,assessed up to 6 months

• R0 resection rate

  From enrollment to the end of surgery,assessed up to 6 months

• 2-year DFS rate

  The longest follow-up time was 2 years from enrollment to disease progression

Study Arms (2)

Group 1

EXPERIMENTAL

Radiotherapy protocol: 5 × 5Gy short-term radiotherapy (D1-5 in the first week) Immunotherapy regimen: Adebrelimab 1200 mg or 20 mg/kg, IV., administered on the first day of each chemotherapy cycle. Chemotherapy regimen: capox regimen: Oxaliplatin 130 mg/m2 IV D1 Capecitabine 1000 mg/m2 Po bid D1 ～ 14 Repeat every 3 weeks for 6 cycles The curative effect was evaluated 2-3 weeks after the completion of 6 cycles of chemotherapy. According to whether the CCR (clinical complete remission) was achieved, TME surgery was required if the CCR was not achieved; If CCR is achieved, TME operation can be performed according to the wishes of the patients. Local resection or observation through anal surgery requires close follow-up to explore the effectiveness and safety of the scheme.

Combination Product: short-term radiotherapy combined with Adebrelimab and capox

Group 2

EXPERIMENTAL

Radiotherapy regimen: long-term radiotherapy 1.8 × 25-28Gy, oral capecitabine in the same period: the standard dose is 825mg/m2, twice a day \[total dose 1650mg/(M2 · d)\], oral radiotherapy day, 5 days a week. Immunotherapy regimen: Adebrelimab 1200 mg or 20 mg/kg, IV., administered on the first day of each chemotherapy cycle. Chemotherapy regimen: capox regimen: Oxaliplatin 130 mg/m2 IV D1 Capecitabine 1000 mg/m2 Po bid D1 ～ 14 Repeat every 3 weeks for 6 cycles The curative effect was evaluated 2-3 weeks after the completion of 6 cycles of chemotherapy. According to whether the CCR (clinical complete remission) was achieved, TME surgery was required if the CCR was not achieved; If CCR is achieved, TME operation can be performed according to the wishes of the patients. Local resection or observation through anal surgery requires close follow-up to explore the effectiveness and safety of the scheme.

Combination Product: long-term radiotherapy combined with Adebrelimab and capox

Interventions

long-term radiotherapy combined with Adebrelimab and capox COMBINATION_PRODUCT

Radiotherapy regimen: long-term radiotherapy 1.8 × 25-28Gy, oral capecitabine in the same period: the standard dose is 825mg/m2, twice a day \[total dose 1650mg/(M2 · d)\], oral radiotherapy day, 5 days a week. Immunotherapy regimen: Adebrelimab 1200 mg or 20 mg/kg, IV., administered on the first day of each chemotherapy cycle. Chemotherapy regimen: capox regimen: Oxaliplatin 130 mg/m2 IV D1 Capecitabine 1000 mg/m2 Po bid D1 ～ 14 Repeat every 3 weeks for 6 cycles The curative effect was evaluated 2-3 weeks after the completion of 6 cycles of chemotherapy. According to whether the CCR (clinical complete remission) was achieved, TME surgery was required if the CCR was not achieved; If CCR is achieved, TME operation can be performed according to the wishes of the patients. Local resection or observation through anal surgery requires close follow-up to explore the effectiveness and safety of the scheme.

Also known as: Adebrelimab, CAPOX

Group 2

short-term radiotherapy combined with Adebrelimab and capox COMBINATION_PRODUCT

Radiotherapy protocol: 5 × 5Gy short-term radiotherapy (D1-5 in the first week) Immunotherapy regimen: Adebrelimab 1200 mg or 20 mg/kg, IV., administered on the first day of each chemotherapy cycle. Chemotherapy regimen: capox regimen: Oxaliplatin 130 mg/m2 IV D1 Capecitabine 1000 mg/m2 Po bid D1 ～ 14 Repeat every 3 weeks for 6 cycles The curative effect was evaluated 2-3 weeks after the completion of 6 cycles of chemotherapy. According to whether the CCR (clinical complete remission) was achieved, TME surgery was required if the CCR was not achieved; If CCR is achieved, TME operation can be performed according to the wishes of the patients. Local resection or observation through anal surgery requires close follow-up to explore the effectiveness and safety of the scheme.

Also known as: Adebrelimab, CAPOX

Group 1

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. sign written informed consent before implementing any test related process;
• \. Patients diagnosed as rectal adenocarcinoma by primary biopsy and histopathological examination;
• \. patients with CT stage ≥ T3 or CN stage N1+, M0 or EMVI (+) or MRF (+) or suspected lateral lymph node metastasis (\>5mm) who are judged by imaging and colonoscopy to be operable and need neoadjuvant therapy.
• \. according to imaging and colonoscopy, the main body of the tumor was located ≤ 10cm from the anal edge;
• \. patients with tumor mismatch repair/microsatellite instability (MMR/MSI) status as MSS;
• \. according to the criteria for evaluating the efficacy of solid tumors (RECIST version 1.1), at least one lesion can be measured by imaging;
• \. the patient has not received any anti-tumor treatment in the past, including but not limited to surgery, radiotherapy, chemotherapy, immunotherapy, targeted therapy, etc;
• \. ECoG score: 0-1;
• \. sufficient organ function, the subject shall meet the following laboratory indicators:
• The absolute value of neutrophils (ANC) ≥ 1.5x109/l without granulocyte colony stimulating factor in the past 14 days.
• Platelets ≥ 100 × 109/l without blood transfusion in recent 14 days.
• Hemoglobin\>9g/dl without blood transfusion or use of erythropoietin in recent 14 days;
• Total bilirubin ≤ 1.5 × upper limit of normal value (ULN);
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in ≤ 2.5 × ULN
• Serum creatinine ≤ 1.5 × ULN and creatinine clearance rate (calculated by Cockcroft Gault formula) ≥ 60 ml/min;

You may not qualify if:

• \. patients diagnosed with other malignant tumors and not cured within 5 years before the first administration (excluding skin basal cell carcinoma, skin squamous cell carcinoma, and/or cancer in situ after radical resection);
• \. Patients with advanced rectal cancer with distant metastasis;
• \. currently participating in intervention clinical research treatment, or having received other research drugs or used research instruments within 4 weeks before the first administration;
• \. have previously received the following therapies: anti-PD-1, anti-PD-L1 or anti-PD-L2 drugs or drugs that stimulate or synergistically inhibit T cell receptors (e.g., CTLA-4, OX-40, CD137);
• \. have received systemic treatment with Chinese patent medicine with anti-tumor indications or drugs with immunomodulatory effect within 2 weeks before the first administration;
• \. active autoimmune diseases requiring systemic treatment (such as the use of disease relieving drugs, glucocorticoids or immunosuppressants) occurred within 2 years before the first administration. Replacement therapy (such as thyroxine, insulin or physiological glucocorticoids for adrenal or pituitary insufficiency, etc.) is not considered as systemic therapy;
• \. the patients were receiving systemic glucocorticoid therapy (excluding local glucocorticoids via nasal spray, inhalation or other routes) or any other form of immunosuppressive therapy within 14 days before the first administration of the study; Note: it is allowed to use physiological doses of glucocorticoids (≤ 10 mg/day of prednisone or equivalent drugs); In the absence of active autoimmune diseases, inhaled or topical steroid and prednisone dose\>10mg/day or equivalent dose of adrenocortical hormone are allowed to replace;
• \. known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation;
• \. those who are known to be allergic to the study drug adebaylimab and the active ingredients or excipients of combined chemotherapy drugs;
• \. have not fully recovered from the toxicity and/or complications caused by any intervention measures before starting treatment (i.e. ≤ grade 1 or reaching the baseline, excluding fatigue or hair loss);
• \. known history of human immunodeficiency virus (HIV) infection (i.e. HIV 1/2 antibody positive);
• \. untreated active hepatitis B (defined as HBsAg positive and HBV-DNA copy number detected is greater than the upper limit of normal value in the laboratory of the research center);
• Note: hepatitis B subjects who meet the following criteria can also be enrolled:
• HBV viral load\<1000 copies/ml (200 iu/ml) before the first administration. Subjects should receive anti HBV treatment during the whole study chemotherapy drug treatment to avoid virus reactivation
• For subjects with anti HBC (+), HBsAg (-), anti HBS (-) and HBV viral load (-), preventive anti HBV treatment is not required, but virus reactivation needs to be closely monitored

Sponsors & Collaborators

• Shandong Provincial Hospital: lead

Study Sites (1)

Shandong Provincial Hospital Affiliated to Shandong First Medical University

Jinan, Shandong, 250021, China

RECRUITING

MeSH Terms

Conditions

Rectal Neoplasms

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Changqing Jing, Professor

  Shandong Provincial Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Feng Tian, Dr.

CONTACT

+86 18866102886; tianfeng@sdu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: November 18, 2025
• First Posted: December 16, 2025
• Study Start: September 12, 2025
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): June 30, 2033
• Last Updated: December 16, 2025

Record last verified: 2025-12

Locations

CN (1)