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

NCT05954429 | Recruiting Phase 2

• 1 other identifier: FDCRC87PJJ
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

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.

Conditions

Colorectal Cancer

Keywords

MSS; serplulimab; fruquintinib

Outcome Measures

Primary Outcomes (1)

• objective response rate (ORR)

  The proportion of participants whose best outcome is complete remission or partial remission

  3 years

Secondary Outcomes (3)

• overall survival (OS)

  3 years

• progression-free survival (PFS)

  3 years

• adverse events

  3 years

Study Arms (1)

Serplulimab+Fruquintinib

EXPERIMENTAL

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.

Drug: serplulimab; Drug: Fruquintinib

Interventions

serplulimab DRUG

Serplulimab is an innovative monoclonal antibody targeting PD-1, developed by Shanghai Henlius Biotech, Inc. 300 mg, q3w Other name: HLX10

Serplulimab+Fruquintinib

Fruquintinib DRUG

5mg (QD) orally for 2 weeks, 1 week off, repeated every 3 weeks until disease progression or intolerable toxicity.

Serplulimab+Fruquintinib

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 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;
• At least one measurable tumor lesion according to RECIST 1.1 criteria
• Good organ function:
• neutrophil ≥1.5\*109/L; Platelet ≥100\*109/L; Hemoglobin ≥9g/dl; Serum albumin ≥3g/dl;
• Thyroid stimulating hormone (TSH) ≤ 1 times the upper limit of normal, T3 and T4 in the normal range;
• bilirubin ≤ 1.5 times the upper limit of normal value; ALT and AST≤ 2 times the upper limit of normal;

You may not qualify if:

• 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

Sponsors & Collaborators

• Fudan University: lead

Study Sites (2)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200000, China

NOT YET RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

HMPL-013

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: July 13, 2023
• First Posted: July 20, 2023
• Study Start: July 20, 2023
• Primary Completion (Estimated): December 28, 2026
• Study Completion (Estimated): August 31, 2027
• Last Updated: January 22, 2026

Record last verified: 2026-01

Locations

CN (2)