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

NCT06521866 | Recruiting Phase 2

• 1 other identifier: VICTORY CRC
• Study Type: interventional
• Target: 208
• Locations: 1 country
• Sites: 10

Brief Summary

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.

Conditions

Advanced Colorectal Carcinoma; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• PFS

  Progression Free Survival

  2 year

Secondary Outcomes (3)

• OS

  2 year

• ORR

  2 year

• Incidence of Side Effect

  2 year

Study Arms (4)

Group A

EXPERIMENTAL

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: Serplulimab; Drug: Chemotherapy; Drug: Targeted therapy

Group B

EXPERIMENTAL

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: Serplulimab; Drug: Chemotherapy; Radiation: SABR; Drug: Targeted therapy

Group C

EXPERIMENTAL

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: Serplulimab; Drug: Chemotherapy; Drug: Targeted therapy

Group D

EXPERIMENTAL

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: Serplulimab; Drug: Chemotherapy; Radiation: SABR; Drug: Targeted therapy

Interventions

Serplulimab DRUG

IV 3 mg/kg on Day 1, q2w

Group A; Group B; Group C; Group D

Chemotherapy DRUG

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

Group A; Group B; Group C; Group D

SABR RADIATION

SABR: 25-60 Gy/5 Fx

Group B; Group D

Targeted therapy DRUG

Cetuximab: 400 mg/m² IV on Day 1, then 250 mg/m² IV weekly ; Bevacizumab: 5 mg/kg IV on Day 1

Group A; Group B; Group C; Group D

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years, any gender;
• 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);
• Treatment-naive patients who have not received standard anti-tumor therapy;
• At least one measurable tumor lesion per RECIST 1.1 criteria;
• ECOG performance status of 0-1;
• 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;
• 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;

You may not qualify if:

• Pathologically diagnosed with other intestinal tumors, such as gastrointestinal stromal tumors;
• No testing for RAS mutation status;
• Resectable metastases or patients wishing to undergo metastasectomy;
• 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.;
• Uncontrolled active bleeding from the primary tumor or bowel obstruction;
• Contraindications to immune checkpoint inhibitors;
• Allergy to the therapeutic drugs and/or their excipients;
• Previous treatment with PD-1 antibodies, PD-L1 antibodies, or CTLA-4 antibodies;
• Received any form of radiation therapy within 4 weeks prior to enrollment;
• Previous or concurrent other malignancies, except adequately treated non-melanoma skin cancer, in situ cervical cancer, or papillary thyroid carcinoma;
• 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;
• History of immunodeficiency, including HIV-positive, or other acquired/congenital immunodeficiency diseases, or history of organ transplantation and allogeneic bone marrow transplantation;
• History of interstitial lung disease (excluding radiation pneumonitis not treated with steroids), non-infectious pneumonia;
• 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;
• 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);

Sponsors & Collaborators

• Fudan University: lead

Study Sites (10)

Fujian Cancer Hospital

Fuzhou, Fujian, 350000, China

NOT YET RECRUITING

The First Affiliated Hospital of Xiamen University

Xiamen, Fujian, 361000, China

NOT YET RECRUITING

Lanzhou Military Region General Hospital

Lanzhou, Gansu, 730000, China

NOT YET RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450000, China

NOT YET RECRUITING

Huai'an Second People's Hospital

Huaian, Jiangsu, 223001, China

NOT YET RECRUITING

Qianfoshan Hospital of Shandong Province

Jinan, Shandong, 250000, China

NOT YET RECRUITING

Taian City Central Hospital

Taian, Shandong, 271000, China

NOT YET RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200030, China

RECRUITING

Yunnan Cancer Hospital

Kunming, Yunnan, 650000, China

NOT YET RECRUITING

Anyang Cancer Hospital

Anyang, 455000, China

NOT YET RECRUITING

MeSH Terms

Interventions

Drug Therapy

Intervention Hierarchy (Ancestors)

Therapeutics

Central Study Contacts

Dawei Li, PhD

CONTACT

13774201693; li_dawei@fudan.edu.cn

Study Design

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

Study Record Dates

• First Submitted: July 22, 2024
• First Posted: July 26, 2024
• Study Start: March 1, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2027
• Last Updated: March 14, 2025

Record last verified: 2025-03

Locations

CN (10)