Serplulimab Combined With CAPEOX + Celecoxib as Neoadjuvant Treatment for Locally Advanced Rectal Cancer

A Phase II Study to Explore the Neoadjuvant Treatment of Serplulimab Combined With CAPEOX + Celecoxib in the Treatment of Locally Advanced Rectal Cancer

Colorectal cancer of Mismatch Repair-proficient (pMMR)/ Microsatellite Stability (MSS) accounts for approximately 85% of all colorectal cancer patients, which might be insensitive to immunotherapy. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy, such as CAPEOX regimen, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Celecoxib, a COX-2 inhibitor, can improve the immune microenvironment and have a potential to synergy with immunotherapy. Chemotherapy can improve the immunogenicity of cancer cells that might enhance the efficacy of immunotherapy. The aim of this study is to explore whether chemotherapy and cyclooxygenase (COX) inhibitors combined with anti-PD-1 monoclonal antibody (mAb) could improve efficacy for resectable colorectal cancer patient with the pMMR/MSS phenotype.

Study Overview

• Status: Recruiting
• Conditions: MSS; Locally Advanced Rectal Carcinoma; pMMR; MSI-L
• Intervention / Treatment: Drug: Oxaliplatin; Drug: Capecitabine; Drug: Celecoxib; Drug: Serplulimab

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kefeng Ding, doctor; Phone Number: +86 13588425440; Email: dingkefeng@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • Second Affiliated Hospital School of Medicine Zhejiang University
      • Contact: Jinjie He, Doctor; Phone Number: +86 13588425440; Email: hjj18279@163.com
      • Principal Investigator: Kefeng Ding, Doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Willing and able to provide written informed consent.
2. Male or female subjects ≧ 18 years ≦ 75 of age.
3. Histological or cytological documentation of adenocarcinoma of the rectum.
4. No previous any systemic anticancer therapy for rectal cancer disease.
5. The lower margin of the tumor is less than 10cm from the anus verge.
6. cT2N1-2M0, cT3N0-2M0, cT4N0-2M0 MSS with MRF(-) assessed by MRI.
7. Primary tumor can be detected by CT or MRI.
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
9. Eligible tumor tissues were identified for MSI/MMR assays.
10. Hepatitis B Surface Antigen (HBsAg) (-).
11. If HBsAg (+) , HBV-DNA must be less than 2500 copies/mL or 500 IU/mL to be enrolled.
12. Patients with HCV antibody (-) or HCV-RNA negative can be enrolled. Aspartate aminotransferase (AST) must be ≤ 3 x ULN for the lab. If HCV-RNA is positive, patients with both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) performed ≤3×ULN could be enrolled. Patients infected with both hepatitis B virus and hepatitis C virus should be excluded (positive for HBsAg or HBcAb and positive for HCV antibodies).

Exclusion Criteria:

1. Patients with recurrent rectal cancer or a history of pelvic radiotherapy.
2. Patients with a history of inflammatory bowel disease.
3. Patients with acquired immunodeficiency syndrome (AIDS-related illnesses) or known human immunodeficiency virus (HIV) disease (HIV1 antibody, HIV2 antibody, HTLV1 antibody positive) should be excluded.
4. Patients who are preparing for or have previously received an organ or bone marrow transplant.
5. History of myocardial infarction, poorly controlled arrhythmias (including QTc interval ≥470 ms in women) in the 6 months prior to enrollment (QTc interval calculated by Fridericia formula).
6. According to New York College of Cardiology (NYHA) standards for Grade III-IV cardiac insufficiency or cardiac color ultrasound: left ventricular ejection fraction (LVEF) <50%.Poor hypertension control (systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥100 mmHg), a past hypertensive crisis or hypertensive encephalopathy.
7. Poor hypertension control (systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥100 mmHg), a past hypertensive crisis or hypertensive encephalopathy.
8. Patients had undergone major surgery within 28 days prior to enrollment. Patients with tumor biopsy or lymph node dissection biopsy were admitted. Patients undergoing enterostomy due to intestinal obstruction were admitted.
9. The patients had previously been treated with other antibodies/drugs that target immune checkpoints, such as PD-1, PD-L1, and cytotoxic T lymphocyte-associated Antigen 4 (CTLA-4).
10. Patients are participating in other clinical studies, or plan to start this study treatment less than 14 days from the end of the previous clinical study.
11. Uncontrolled tumor-related pain.
12. A known history of severe allergy to any monoclonal antibody.
13. Known to be allergic or intolerance to any oxaliplatin and capecitabine ingredients.
14. Pregnant or lactating women.
15. The investigators determined that the patient had other factors that might have led to the early termination of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Serplulimab+CAPEOX+celecoxib; Participants will receive serplulimab 300 mg every 3 weeks (Q3W) concurrently with CAPEOX regimen: Oxaliplatin(130mg/m2) on day 1 of each cycle and Capecitabine, 1000mg/m2, PO, BID, day1-14, q3w and celecoxib, 200mg, PO, BID, day1-21, q3w. Treatment repeats every 3 weeks for 4-8 cycles followed by surgery (total mesorectal excision, TME).

Drug: Oxaliplatin; Given IV; Other Names: OHP; Drug: Capecitabine; Given PO; Other Names: Xeloda; Drug: Celecoxib; celebrex; Other Names: Given PO; Drug: Serplulimab; Serplulimab is an innovative monoclonal antibody targeting PD-1, developed by Shanghai Henlius Biotech, Inc. 300 mg, q3w. For the timing of serplulimab, there is a subgroup developed, all enrolled patients will be divided into 2 subgroups in 1:1 ratio, the fasting group and the control group. For the fasting group patients, fasting starts from 8 p.m. the day before treatment and concludes at 12 p.m. on the treatment day, water is allowed. For the control group patients, they have meals according to their habits.; Other Names: HLX10

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological complete response rates	Proportion of patients experiencing a pCR to perioperative PD-1 antibody	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major pathological response rates	The proportion of patients experiencing a major pathological response to perioperative PD-1 antibody	1 year
Rate of clinical complete response rate (cCR)	Proportion of patients experiencing a cCR to perioperative PD-1 antibody	1 year
R0 resection rates	The proportion of patients achieved a complete resection with negative margin	1 year
Treatment-related adverse events.	Assessed by evaluation of treatment-related adverse events.	1 year
Detection of MRD	To detect ctDNA in peripheral blood before and after treatment	1year
single cell sequence	Use single cell sequence to describe changes in the microenvironment of rectal cancer before and after treatment	1year
Disease Free Survival	Defined as the interval from enrollment to locoregional or metastatic recurrence or the appearance or a secondary colorectal cancer or death, whichever occurs first	3years

Collaborators and Investigators

• Sponsor: Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2023
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: February 7, 2023
• First Submitted That Met QC Criteria: February 7, 2023
• First Posted (Actual): February 16, 2023

Study Record Updates

• Last Update Posted (Actual): March 5, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Celecoxib; Rectal cancer; neoadjuvant therapy; Serplulimab; CAPEOX
• 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; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Nucleic Acids, Nucleotides, and Nucleosides; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Amides; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Benzene Derivatives; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Benzenesulfonamides; Sulfonamides; Sulfones; Fluorouracil; Pyrazoles; Capecitabine; Oxaliplatin; Celecoxib
• Other Study ID Numbers: ASTRUM-REC01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No