A Study to Explore the Third-line Treatment of Fruquintinib Combined With Serplulimab in Advanced Non-isolated Hepatic Metastatic Colorectal Cancer: a Single-center, Phase 2 Study

Trial Title: A Study to Explore the Third-line Treatment of Fruquintinib Combined With Serplulimab in Advanced Non-isolated Hepatic Metastatic Colorectal Cancer: a Single-center, Phase 2 Study

NCT ID: NCT05954429

Condition: Colorectal Cancer

Conditions: Official terms:
Colorectal Neoplasms

Conditions: Keywords:
MSS
serplulimab
fruquintinib

Study type: Interventional

Study phase: Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: serplulimab
Description: Serplulimab is an innovative monoclonal antibody targeting PD-1, developed by Shanghai Henlius Biotech, Inc. 300 mg, q3w Other name: HLX10
Arm group label: Serplulimab+Fruquintinib

Intervention type: Drug
Intervention name: Fruquintinib
Description: 5mg (QD) orally for 2 weeks, 1 week off, repeated every 3 weeks until disease progression or intolerable toxicity.
Arm group label: Serplulimab+Fruquintinib

Summary: The aim of this clinical trial is to learn about efficacy of fruquintinib combined with serplulimab in patients with microsatellite stabilized mCRC who have failed standard therapy. The main purpose is to explore efficacy, safety and tolerability of the treatment. At the same time, the correlation between biomarkers (including ctDNA, TPS, CPS, tumor mutation burden, lymphocyte subpopulation, cytokines, TCR, intestinal microbes, etc.) and the efficacy and drug resistance mechanism will be analyzed, which could provide reference for determining the advantaged group.

Detailed description: Serplulimab is an anti-PD-1 monoclonal antibody, and fruquintinib is a tyrosine kinase inhibitor that inhibits tumor angiogenesis. Studies have shown that immunotherapy combined with fruquintinib has preliminary efficacy in the treatment of colorectal cancer. Whether serplulimab combined with fruquintinib can improve the prognosis of patients with colorectal cancer remains to be determined. Therefore, the study is to evaluate the efficacy and safety of serplulimab combination with fruquintinib in patients with microsatellite stabilized mCRC who have failed standard therapy.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Age ≥18 years old, both sexes; - Patients with histologically or cytologically confirmed unresectable and metastatic CRC - Non-isolated hepatic metastasis: including no liver metastasis or liver metastasis accompanied by other metastatic lesions, such as lung metastasis, peritoneal metastasis, etc - Before enrollment, the tumor tissue was pMMR by immunohistochemistry, or MSS or MSI-L by PCR or NGS; - Have received standard treatment in the past and developed disease progression or intolerance to standard treatment based on RECIST 1.1 during or after standard treatment. Standard treatment should include: 1. Fluorouracil, oxaliplatin and irinotecan 2. With or without anti-VEGF monoclonal antibody 3. For RAS wild-type patients, combined with anti-EGFR monoclonal antibody 4. For patients with BRAF mutations, BRAF inhibitor therapy is recommended when drugs are available - Patients with ECOG score of 0-2 and expected survival time ≥3 months, patients who can cooperate to observe adverse reactions and efficacy; - At least one measurable tumor lesion according to RECIST 1.1 criteria - Good organ function: 1. neutrophil ≥1.5*109/L; Platelet ≥100*109/L; Hemoglobin ≥9g/dl; Serum albumin ≥3g/dl; 2. Thyroid stimulating hormone (TSH) ≤ 1 times the upper limit of normal, T3 and T4 in the normal range; 3. bilirubin ≤ 1.5 times the upper limit of normal value; ALT and AST≤ 2 times the upper limit of normal; 4. Serum creatinine ≤ 1.5 times the upper limit of normal, creatinine clearance ≥60ml/min; 5. International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times the upper limit of the normal range, unless the patient is receiving anticoagulant therapy and the PT value is within the intended range for anticoagulant therapy; 6. Activated partial thromboplastin time (aPTT) ≤ 1.5 times the upper limit of normal; - There were no serious concomitant diseases that could make the survival time less than 5 years; - Negative pregnancy test in female subjects (for female patients of childbearing potential); Infertile female patients; - Male patients of childbearing potential and female patients of childbearing potential and at risk of pregnancy must agree to use adequate contraception for the entire duration of the study and for 12 months after receiving treatment with the protocol; - Signed and dated informed consent indicating that the patient has been informed about all relevant aspects of the study; - Patients who are willing and able to comply with the visit schedule, treatment plan, laboratory tests, and other study procedures; - Willing to comply with the arrangement during the study period can not participate in any other clinical research on drugs and medical devices Exclusion Criteria: - Pathological diagnosis of other intestinal tumors, such as gastrointestinal stromal tumor; - Tumor tissues were dMMR detected by immunohistochemistry, or MSI-H detected by PCR or NGS - Prior treatment with PD-1 antibody, PD-L1 antibody, or CTLA-4 antibody; - Previous or concurrent history of other malignant tumors, excluding adequately treated non-melanoma skin cancer, cervical carcinoma in situ and thyroid papillary carcinoma; - Active autoimmune disease, history of autoimmune disease (such as interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes); It does not include autoimmune-mediated hypothyroidism treated with stable doses of thyroid replacement hormone; Type I diabetes on stable doses of insulin; Vitiligo or cured childhood asthma/allergy without any intervention in adulthood; - A history of immunodeficiency, including HIV positive, other acquired or congenital immunodeficiency diseases, or organ transplantation or allogeneic bone marrow transplantation; - Contraindications to antiangiogenic drugs (such as active bleeding, gastrointestinal bleeding, hemoptysis, etc.); - History of interstitial lung disease (excluding radiation pneumonitis without steroid treatment) and non-infectious pneumonia; - Patients with active pulmonary tuberculosis infection detected by medical history or CT examination, or with a history of active pulmonary tuberculosis infection within 1 year before enrollment, or with a history of active pulmonary tuberculosis infection more than 1 year before enrollment but without regular treatment; - The subject has active hepatitis B (HBV DNA ≥2000 IU/mL or 104 copies/mL), hepatitis C (hepatitis C antibody positive and HCV-RNA above the detection limit of the assay) - Severe cardiopulmonary and renal dysfunction; - Have hypertension that is not well controlled with antihypertensive medication (systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90mmHg); - A history of psychotropic substance abuse, alcohol or drug abuse; - Other factors that may affect subject safety or trial compliance as judged by the investigator. Severe medical conditions requiring concomitant treatment (including mental illness), serious laboratory abnormalities, or other family or social factors

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Fudan University Shanghai Cancer Center

Address:
City: Shanghai
Zip: 200000
Country: China

Contact:
Last name: Junjie Peng

Phone: 021-64175590
Email: pengjj67@hotmail.com

Start date: July 20, 2023

Completion date: August 31, 2026

Lead sponsor:
Agency: Junjie Peng
Agency class: Other

Source: Fudan University

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05954429