A Prospective, Multicenter, Single-Arm Phase II Exploratory Study of Serplulimab Combined With Oncolytic Virus H101, Short-Course Radiotherapy, and XELOX Chemotherapy as Total Neoadjuvant Treatment for Locally Advanced (cT1-3N0M0) Rectal Cancer

A Prospective, Multicenter, Single-Arm Phase II Study of Serplulimab Combined With Oncolytic Virus H101, Short-Course Radiotherapy, and XELOX Chemotherapy as Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer (cT1-3N0M0)

This study aims to evaluate the safety and effectiveness of a combination treatment including a PD-1 inhibitor (serplulimab), oncolytic virus H101, short-course radiotherapy, and XELOX chemotherapy as total neoadjuvant therapy in patients with locally advanced low rectal cancer (cT1-3N0M0).

In this prospective, multicenter, single-arm phase II study, eligible patients will receive a standardized treatment regimen consisting of intratumoral injection of oncolytic virus H101, short-course radiotherapy, chemotherapy, and immunotherapy over multiple cycles. Tumor response will be assessed using imaging, endoscopy, and clinical evaluation after completion of treatment.

The primary objective is to determine the 1-year clinical complete response rate. Secondary outcomes include tumor response rate, organ preservation rate, survival outcomes, and treatment safety.

The results of this study may help improve treatment strategies for rectal cancer, increase the rate of complete response, and provide more opportunities for organ preservation while maintaining safety.

Study Overview

• Status: Not yet recruiting
• Conditions: Rectal Neoplasms; Rectal Adenocarcinoma
• Intervention / Treatment: Drug: Serplulimab; Biological: Oncolytic Virus H101; Drug: XELOX Chemotherapy; Radiation: Short-course Radiotherapy

Detailed Description

Rectal cancer is a common malignancy with a significant impact on patient survival and quality of life. For patients with locally advanced rectal cancer, the current standard treatment typically includes neoadjuvant chemoradiotherapy followed by surgery. Although this approach can achieve tumor control, the rate of complete response remains limited, and surgery may result in permanent stoma or impaired bowel, urinary, and sexual function. Therefore, there is a need to develop more effective treatment strategies that can improve tumor response and increase the chance of organ preservation.

Most rectal cancers are mismatch repair-proficient or microsatellite stable (pMMR/MSS), which generally show limited response to immunotherapy alone. Recent studies suggest that combination strategies may enhance treatment efficacy by modifying the tumor microenvironment and improving immune response.

This study is designed to evaluate a novel combination treatment approach that includes a PD-1 inhibitor (serplulimab), an oncolytic virus (H101), short-course radiotherapy, and XELOX chemotherapy as total neoadjuvant therapy. The oncolytic virus H101 selectively infects and destroys tumor cells while stimulating anti-tumor immune responses. Radiotherapy may further enhance immune activation by promoting tumor antigen release, and chemotherapy can improve tumor sensitivity to treatment. The combination of these therapies is expected to have a synergistic effect. :contentReference[oaicite:0]{index=0}

This is a prospective, multicenter, single-arm phase II clinical trial. Approximately 20 patients with low rectal adenocarcinoma (cT1-3N0M0) will be enrolled. All participants will receive a standardized treatment regimen consisting of intratumoral injections of H101, short-course radiotherapy, and systemic treatment with serplulimab and XELOX chemotherapy over multiple cycles. :contentReference[oaicite:1]{index=1}

Tumor response will be evaluated after completion of the total neoadjuvant therapy using imaging, endoscopy, and clinical assessments. Patients who achieve clinical complete response may enter a non-surgical management strategy with close follow-up, while others may proceed to surgery based on clinical evaluation.

The primary endpoint of this study is the 1-year clinical complete response rate. Secondary endpoints include objective response rate, organ preservation rate, tumor downstaging, recurrence-free survival, disease-free survival, overall survival, and safety outcomes. :contentReference[oaicite:2]{index=2}

The findings of this study may provide evidence for a new treatment strategy for rectal cancer that improves tumor response and increases the possibility of organ preservation while maintaining acceptable safety.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Bo Yi, MD; Phone Number: +86-137-8617-9533; Email: yibo2018pro@126.com

Study Locations

• China
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 400030
      • Chongqing University Cancer Hospital
      • Contact: Bo Yi, MD; Phone Number: +86-137-8617-9533; Email: yibo2018pro@126.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

- Participants must meet all of the following criteria:

1. Age 18 to 80 years, male or female.
2. Histologically confirmed low rectal adenocarcinoma, with tumor located ≤5 cm from the anal verge.
3. Clinical stage T1-3N0M0 according to AJCC staging criteria.
4. Mismatch repair-proficient (pMMR) or microsatellite stable (MSS) tumor confirmed by immunohistochemistry or genetic testing.
5. No prior anti-tumor treatment.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, with an expected survival of at least 3 months.

7. Adequate organ function, including:

   • Absolute neutrophil count ≥1.5 × 10^9/L
   • Platelet count ≥100 × 10^9/L
   • Hemoglobin ≥9 g/dL
   • Serum albumin ≥3 g/dL
   • Total bilirubin ≤1.5 × upper limit of normal (ULN)
   • ALT and AST ≤2 × ULN
   • Serum creatinine ≤1.5 × ULN or creatinine clearance ≥60 mL/min
   • INR or PT ≤1.5 × ULN, and aPTT ≤1.5 × ULN
8. Thyroid function within normal range or adequately controlled.
9. Negative pregnancy test for women of childbearing potential.
10. Willingness to use effective contraception during the study and for 12 months after treatment.
11. Ability to understand and willingness to sign a written informed consent form.
12. Willingness and ability to comply with study procedures and follow-up.

Exclusion Criteria:

• Participants will be excluded if they meet any of the following criteria:

  1. Histology other than rectal adenocarcinoma (e.g., gastrointestinal stromal tumor, lymphoma).
  2. Prior pelvic radiotherapy.
  3. Prior treatment with PD-1, PD-L1, or CTLA-4 inhibitors.
  4. Known allergy to study drugs or their components.
  5. History of other malignancies, except adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix, or papillary thyroid carcinoma.
  6. Active autoimmune disease or history of autoimmune disease requiring systemic treatment.
  7. Immunodeficiency, including HIV infection, or history of organ transplantation.
  8. History of interstitial lung disease or non-infectious pneumonitis.
  9. Active tuberculosis infection or history of untreated tuberculosis.
  10. Active hepatitis B or hepatitis C infection.
  11. Severe cardiovascular, pulmonary, or renal disease.
  12. Uncontrolled hypertension despite medication.
  13. History of substance abuse (alcohol or drugs).
  14. Active uncontrolled infection.
  15. Use of systemic immunosuppressive therapy.
  16. Pregnant or breastfeeding women.
  17. Any condition that, in the investigator's opinion, may interfere with study participation or safety.

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 + H101 + Short-course Radiotherapy + XELOX; Participants with low rectal adenocarcinoma (cT1-3N0M0) will receive total neoadjuvant therapy consisting of intratumoral oncolytic virus H101, short-course radiotherapy, serplulimab, and XELOX chemotherapy. H101 will be administered on Day 1 of Cycle 1 and Day 1 of Cycle 4. Short-course radiotherapy will be delivered during treatment. Serplulimab and XELOX chemotherapy will be administered every 3 weeks according to the study protocol. Tumor response will be assessed after completion of treatment.

Drug: Serplulimab; Serplulimab is a humanized monoclonal antibody targeting programmed cell death protein-1 (PD-1). It will be administered intravenously at a fixed dose of 300 mg on Day 1 of each 3-week cycle for a total of 6 cycles. Serplulimab is given in combination with chemotherapy, radiotherapy, and oncolytic virus therapy as part of total neoadjuvant treatment. The aim is to enhance anti-tumor immune response and improve treatment efficacy.; Biological: Oncolytic Virus H101; H101 is a recombinant human adenovirus type 5 oncolytic virus that selectively replicates in and lyses tumor cells while stimulating anti-tumor immune responses. It will be administered by intratumoral injection on Day 1 of Cycle 1 and Day 1 of Cycle 4. The dose will be determined based on tumor size. H101 is used in combination with immunotherapy, chemotherapy, and radiotherapy to enhance tumor cell killing and improve immune activation.; Drug: XELOX Chemotherapy; XELOX chemotherapy consists of oxaliplatin and capecitabine. Oxaliplatin will be administered intravenously at a dose of 130 mg/m² on Day 1, and capecitabine will be given orally at a dose of 1000 mg/m² twice daily from Day 1 to Day 14 of each 3-week cycle. A total of 6 cycles will be administered. Chemotherapy is combined with immunotherapy, radiotherapy, and oncolytic virus therapy to improve tumor response.; Radiation: Short-course Radiotherapy; Short-course radiotherapy will be delivered to the rectal tumor using intensity-modulated radiation therapy (IMRT). The total dose is 25 Gy administered in 5 fractions over one week. Radiotherapy is given during the treatment course in combination with immunotherapy, chemotherapy, and oncolytic virus therapy. It aims to enhance local tumor control and stimulate anti-tumor immune response.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year Clinical Complete Response Rate	Clinical complete response (cCR) is defined as no evidence of residual tumor based on digital rectal examination, endoscopy showing mucosal healing or scar, and imaging (MRI or CT) without tumor signal or metabolic activity, and no distant metastasis. The proportion of patients achieving cCR and maintaining it for at least 1 year will be evaluated.	1 year after completion of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	The proportion of participants who achieve complete response (CR) or partial response (PR) based on imaging assessments according to RECIST criteria.	Up to 6 months after treatment initiation
Organ Preservation Rate	The proportion of patients who achieve clinical complete response and avoid radical surgery, thereby preserving the rectum.	1 year after completion of treatment
Disease-Free Survival	Time from treatment initiation to the occurrence of disease recurrence, metastasis, or death from any cause.	Up to 3 years
Overall Survival	Time from treatment initiation to death from any cause.	Up to 3 years
Incidence of Adverse Events	The incidence and severity of treatment-related adverse events will be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.	From treatment initiation up to 3 years

Collaborators and Investigators

• Sponsor: Chongqing University Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: April 15, 2026
• First Submitted That Met QC Criteria: April 15, 2026
• First Posted (Actual): April 22, 2026

Study Record Updates

• Last Update Posted (Actual): April 22, 2026
• Last Update Submitted That Met QC Criteria: April 15, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Combination Therapy; Rectal Cancer; Total Neoadjuvant Therapy; PD-1 Inhibitor; Organ Preservation; Serplulimab; Oncolytic Virus H101; XELOX Chemotherapy; Short-course Radiotherapy; Clinical Complete Response
• 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: 20260115101749430

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared due to patient privacy concerns and institutional data protection policies. De-identified data may be available upon reasonable request to the corresponding investigator, subject to approval.

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