A Study to Explore the Third-line Treatment of Fruquintinib Combined With Serplulimab in Advanced Non-liver-limited Metastatic Colorectal Cancer: a Single-center, Phase 2 Study
Overview
- Phase
- Phase 2
- Intervention
- serplulimab
- Conditions
- Colorectal Cancer
- Sponsor
- Fudan University
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- objective response rate (ORR)
- Status
- Recruiting
- Last Updated
- 3 months ago
Overview
Brief 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.
Investigators
Junjie Peng
Prof.
Fudan University
Eligibility Criteria
Inclusion Criteria
- •Age ≥18 years old, both sexes;
- •Patients with histologically or cytologically confirmed unresectable and metastatic CRC
- •non-liver-limited 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:
- •Fluorouracil, oxaliplatin and irinotecan
- •With or without anti-VEGF monoclonal antibody
- •For RAS wild-type patients, combined with anti-EGFR monoclonal antibody
- •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;
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)
Arms & Interventions
Serplulimab+Fruquintinib
Participants will receive serplulimab 300 mg every 3 weeks (Q3W) concurrently with fruquintinib regimen: 5mg (QD) orally for 2 weeks, 1 week off, repeated every 3 weeks. Treatment repeats every 3 weeks until disease progression or intolerable toxicity.
Intervention: serplulimab
Serplulimab+Fruquintinib
Participants will receive serplulimab 300 mg every 3 weeks (Q3W) concurrently with fruquintinib regimen: 5mg (QD) orally for 2 weeks, 1 week off, repeated every 3 weeks. Treatment repeats every 3 weeks until disease progression or intolerable toxicity.
Intervention: Fruquintinib
Outcomes
Primary Outcomes
objective response rate (ORR)
Time Frame: 3 years
The proportion of participants whose best outcome is complete remission or partial remission
Secondary Outcomes
- overall survival (OS)(3 years)
- progression-free survival (PFS)(3 years)
- adverse events(3 years)