Phase II Study of Serplulimab Combined with First-Line Targeted Therapy, Chemotherapy, and Radiation in Advanced Colorectal Cancer

A Prospective, Randomized, Phase II, Multicenter Clinical Study of Serplulimab Combined with First-Line Targeted Therapy and Chemotherapy with or Without Radiation in the First-Line Treatment of Advanced Colorectal Cancer

Study Title:

A Prospective, Randomized, Phase II, Multicenter Clinical Study of Serplulimab Combined with Targeted Therapy, Chemotherapy, and Optional Radiotherapy in Advanced Colorectal Cancer

Study Objective:

To explore the efficacy and safety of immune checkpoint inhibitor combined with targeted therapy and chemoradiotherapy in locally advanced unresectable or metastatic colorectal cancer.

Study Population:

Patients with left-sided wild-type, right-sided, or RAS-mutant advanced colorectal cancer who have not received systemic treatment.

Study Endpoints:

Progression-free survival (PFS), objective response rate (ORR), overall survival (OS), safety, and R0 resection rate.

Study Design:

Prospective, randomized Phase II clinical study.

Study Overview

• Status: Recruiting
• Conditions: Immunotherapy; Advanced Colorectal Carcinoma
• Intervention / Treatment: Drug: Chemotherapy; Radiation: SABR; Drug: Serplulimab; Drug: Targeted therapy

• Study Type: Interventional
• Enrollment (Estimated): 208
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Dawei Li, PhD; Phone Number: 13774201693; Email: li_dawei@fudan.edu.cn

Study Locations

• China
  • Anyang, China, 455000
    • Not yet recruiting
    • Anyang Cancer Hospital
    • Contact: Yanjun Wang
  • Fujian
    • Fuzhou, Fujian, China, 350000
      • Not yet recruiting
      • Fujian Cancer Hospital
      • Contact: Shen Guan
    • Xiamen, Fujian, China, 361000
      • Not yet recruiting
      • The First Affiliated Hospital of Xiamen University
      • Contact: Guoqiang Su
  • Gansu
    • Lanzhou, Gansu, China, 730000
      • Not yet recruiting
      • Lanzhou Military Region General Hospital
      • Contact: Shoucheng Ma
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Not yet recruiting
      • The First Affiliated Hospital of Zhengzhou University
      • Contact: Jinbo Liu
  • Jiangsu
    • Huaian, Jiangsu, China, 223001
      • Not yet recruiting
      • Huai'an Second People's Hospital
      • Contact: Haijian Zhao
  • Shandong
    • Jinan, Shandong, China, 250000
      • Not yet recruiting
      • Qianfoshan hospital of Shandong Province
      • Contact: Hui Yang
    • Taian, Shandong, China, 271000
      • Not yet recruiting
      • Taian City Central Hospital
      • Contact: Gang Cui
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Contact: Dawei Li; Phone Number: 13774201693; Email: li_dawei@fudan.edu.cn
  • Yunnan
    • Kunming, Yunnan, China, 650000
      • Not yet recruiting
      • Yunnan Cancer Hospital
      • Contact: Xinyi Cai

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥ 18 years, any gender;

2. Histologically confirmed metastatic colorectal cancer (Stage IV, UICC), with initially unresectable metastases or refusal of surgery;

   • Primary tumor located in the distal transverse colon, descending colon, sigmoid colon, and rectum, and RAS (KRAS and NRAS) and BRAF wild-type (Cohorts A and B);
   • Primary tumor located in the cecum, ascending colon, and proximal transverse colon, and RAS (KRAS and NRAS) mutant-type (Cohorts C and D);
3. Treatment-naive patients who have not received standard anti-tumor therapy;
4. At least one measurable tumor lesion per RECIST 1.1 criteria;
5. ECOG performance status of 0-1;

6. Patients with an expected survival time of ≥ 3 months and good organ function:

   • (1) Neutrophils ≥ 1.5 * 10^9/L; platelets ≥ 100 * 10^9/L; hemoglobin ≥ 9 g/dL; serum albumin ≥ 3 g/dL;
   • (2) Thyroid-stimulating hormone (TSH) ≤ upper limit of normal (ULN), T3 and T4 within normal ranges;
   • (3) Bilirubin ≤ 1.5 times ULN; ALT and AST ≤ 2 times ULN;
   • (4) Serum creatinine ≤ 1.5 times ULN, creatinine clearance rate ≥ 60 mL/min;
   • (5) International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN, unless the patient is receiving anticoagulant therapy and PT is within the expected therapeutic range of anticoagulants;
   • (6) Activated partial thromboplastin time (aPTT) ≤ 1.5 times ULN;
7. Female patients of childbearing potential must have a negative pregnancy test; female patients not of childbearing potential; male patients of reproductive potential and female patients of reproductive potential and at risk of pregnancy must agree to use adequate contraception throughout the study period, continuing until 12 months after the last dose of study treatment;
8. Signed and dated informed consent form indicating that the patient has been informed of all pertinent aspects of the study;
9. Patients willing and able to comply with visit schedule, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

1. Pathologically diagnosed with other intestinal tumors, such as gastrointestinal stromal tumors;
2. No testing for RAS mutation status;
3. Resectable metastases or patients wishing to undergo metastasectomy;
4. Prior systemic therapy. Systemic therapy includes all of the following: chemotherapy agents such as fluoropyrimidines, irinotecan, and oxaliplatin, VEGF monoclonal antibodies (e.g., bevacizumab), EGFR monoclonal antibodies (cetuximab or panitumumab), small molecule TKIs, immune checkpoint inhibitors, etc.;
5. Uncontrolled active bleeding from the primary tumor or bowel obstruction;
6. Contraindications to immune checkpoint inhibitors;
7. Allergy to the therapeutic drugs and/or their excipients;
8. Previous treatment with PD-1 antibodies, PD-L1 antibodies, or CTLA-4 antibodies;
9. Received any form of radiation therapy within 4 weeks prior to enrollment;
10. Previous or concurrent other malignancies, except adequately treated non-melanoma skin cancer, in situ cervical cancer, or papillary thyroid carcinoma;
11. Active autoimmune disease or history of autoimmune disease (e.g., interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes); except autoimmune-mediated hypothyroidism on stable doses of thyroid replacement hormone, type I diabetes on stable doses of insulin, vitiligo, or childhood asthma/allergies that have resolved and do not require intervention in adulthood;
12. History of immunodeficiency, including HIV-positive, or other acquired/congenital immunodeficiency diseases, or history of organ transplantation and allogeneic bone marrow transplantation;
13. History of interstitial lung disease (excluding radiation pneumonitis not treated with steroids), non-infectious pneumonia;
14. Active tuberculosis infection identified by history or CT scan, or history of active tuberculosis infection within 1 year prior to enrollment, or history of active tuberculosis infection more than 1 year ago but without proper treatment;
15. Active hepatitis B (HBV DNA ≥ 2000 IU/mL or 10^4 copies/mL), active hepatitis C (HCV antibody positive and HCV-RNA above the detection limit);
16. Severe dysfunction of the heart, lungs, or kidneys;
17. Hypertension not well controlled by antihypertensive medications (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg);
18. History of substance abuse, alcoholism, or drug addiction;
19. Any other factors judged by the investigator to potentially affect the safety or compliance of the patient with the study, such as serious concomitant disease (including mental illness), serious laboratory abnormalities, or other familial or social factors.

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; Group A (Left-sided wild-type): Induction Treatment (12 cycles): Serplulimab: IV 3 mg/kg on Day 1, q2w Cetuximab: 400 mg/m² IV infusion (1st infusion >2 hours, then 250 mg/m² IV infusion ≥60 min), weekly mFOLFOX6: Oxaliplatin: 85 mg/m² IV over 2 hrs, Day 1 LV: 400 mg/m² IV over 2 hrs, Day 1 5-FU: 400 mg/m² IV push, Day 1; 2400 mg/m² IV over 46-48 hrs q2w Maintenance therapy: Serplulimab: IV 3 mg/kg on Day 1, q2w Cetuximab: 400 mg/m² IV infusion (1st infusion >2 hours, then 250 mg/m² IV infusion ≥60 min), weekly 5-FU/LV: LV: 400 mg/m² IV over 2 hrs, Day 1 5-FU: 400 mg/m² IV push, Day 1; 2400 mg/m² IV over 46-48 hrs q2w	Drug: Chemotherapy; Induction therapy：Oxaliplatin: 85 mg/m² IV on Day 1 Leucovorin (LV): 400 mg/m² IV on Day 1 5-FU: 400 mg/m² IV bolus on Day 1, then 2400 mg/m² continuous IV infusion over 46-48 hours Maintenance therapy: Leucovorin (LV): 400 mg/m² IV on Day 1 5-FU: 400 mg/m² IV bolus on Day 1, then 2400 mg/m² continuous IV infusion over 46-48 hours; Drug: Serplulimab; IV 3 mg/kg on Day 1, q2w; Drug: Targeted therapy; Cetuximab: 400 mg/m² IV on Day 1, then 250 mg/m² IV weekly ; Bevacizumab: 5 mg/kg IV on Day 1
Experimental: Group B; Group B (Left-sided wild-type): One cycle of Serplulimab combined with Cetuximab and chemotherapy, followed by Stereotactic ablative radiotherapy（SABR: 25-60 Gy/5 Fx）, then continued Serplulimab combined with Cetuximab and chemotherapy.	Drug: Chemotherapy; Induction therapy：Oxaliplatin: 85 mg/m² IV on Day 1 Leucovorin (LV): 400 mg/m² IV on Day 1 5-FU: 400 mg/m² IV bolus on Day 1, then 2400 mg/m² continuous IV infusion over 46-48 hours Maintenance therapy: Leucovorin (LV): 400 mg/m² IV on Day 1 5-FU: 400 mg/m² IV bolus on Day 1, then 2400 mg/m² continuous IV infusion over 46-48 hours; Radiation: SABR; SABR: 25-60 Gy/5 Fx; Drug: Serplulimab; IV 3 mg/kg on Day 1, q2w; Drug: Targeted therapy; Cetuximab: 400 mg/m² IV on Day 1, then 250 mg/m² IV weekly ; Bevacizumab: 5 mg/kg IV on Day 1
Experimental: Group C; Group C (Right-sided or RAS-mutant): Induction Treatment (12 cycles): Serplulimab: IV 3 mg/kg on Day 1, q2w Bevacizumab: 5 mg/kg IV on Day 1, q2w mFOLFOX6: Oxaliplatin: 85 mg/m² IV over 2 hrs, Day 1 LV: 400 mg/m² IV over 2 hrs, Day 1 5-FU: 400 mg/m² IV push, Day 1; 2400 mg/m² IV over 46-48 hrs q2w Maintenance Treatment: Serplulimab: IV 3 mg/kg on Day 1, q2w Bevacizumab: 5 mg/kg IV on Day 1, q2w 5-FU/LV: LV: 400 mg/m² IV over 2 hrs, Day 1 5-FU: 400 mg/m² IV push, Day 1; 2400 mg/m² IV over 46-48 hrs q2w	Drug: Chemotherapy; Induction therapy：Oxaliplatin: 85 mg/m² IV on Day 1 Leucovorin (LV): 400 mg/m² IV on Day 1 5-FU: 400 mg/m² IV bolus on Day 1, then 2400 mg/m² continuous IV infusion over 46-48 hours Maintenance therapy: Leucovorin (LV): 400 mg/m² IV on Day 1 5-FU: 400 mg/m² IV bolus on Day 1, then 2400 mg/m² continuous IV infusion over 46-48 hours; Drug: Serplulimab; IV 3 mg/kg on Day 1, q2w; Drug: Targeted therapy; Cetuximab: 400 mg/m² IV on Day 1, then 250 mg/m² IV weekly ; Bevacizumab: 5 mg/kg IV on Day 1
Experimental: Group D; Group D (Right-sided or RAS-mutant): One cycle of Serplulimab combined with Bevacizumab and chemotherapy, followed by Stereotactic ablative radiotherapy（SABR: 25-60 Gy/5 Fx）, then continued Serplulimab combined with Bevacizumab and chemotherapy.	Drug: Chemotherapy; Induction therapy：Oxaliplatin: 85 mg/m² IV on Day 1 Leucovorin (LV): 400 mg/m² IV on Day 1 5-FU: 400 mg/m² IV bolus on Day 1, then 2400 mg/m² continuous IV infusion over 46-48 hours Maintenance therapy: Leucovorin (LV): 400 mg/m² IV on Day 1 5-FU: 400 mg/m² IV bolus on Day 1, then 2400 mg/m² continuous IV infusion over 46-48 hours; Radiation: SABR; SABR: 25-60 Gy/5 Fx; Drug: Serplulimab; IV 3 mg/kg on Day 1, q2w; Drug: Targeted therapy; Cetuximab: 400 mg/m² IV on Day 1, then 250 mg/m² IV weekly ; Bevacizumab: 5 mg/kg IV on Day 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	Progression Free Survival	2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Objective Response Rate	2 year
OS	Overall Survial	2 year
Incidence of Side Effect	Side Effect	2 year

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: July 22, 2024
• First Submitted That Met QC Criteria: July 25, 2024
• First Posted (Actual): July 26, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 11, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms
• Other Study ID Numbers: VICTORY CRC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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