A Phase II Clinical Study of Aipalolitovorelizumab (QL1706) Combined With Fruquintinib in the Treatment of Immunodominant pMMR/MSS Metastatic Colorectal Cancer That Has Failed Second-line or Above Treatment

NCT07229872 | Not Yet Recruiting Phase 2

• 1 other identifier: QL-CRC-QIBA-3007
• Study Type: interventional
• Target: 18
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to explore the preliminary efficacy and tolerability of Aipalolitovorelizumab (QL1706) in combination with fruquintinib for the treatment of metastatic colorectal cancer patients with immunodominant pMMR/MSS type who have failed second-line or above treatment. It is an open-label, single-arm, single-center phase II trial. The main questions it aims to answer are: What is the objective response rate (ORR) of this combination therapy? What are the outcomes in terms of progression-free survival (PFS), overall survival (OS), and disease control rate (DCR)? What are the safety profiles and tolerability of the treatment? Participants will receive: Aipalolitovorelizumab (QL1706) injection at a dose of 5mg/kg, administered intravenously on Day 1 of each 3-week treatment cycle. Fruquintinib at a dose of 5mg per day, taken orally continuously for the first 2 weeks of each 3-week cycle, followed by 1 week of withdrawal. The treatment will continue until disease progression as assessed by RECIST v1.1 criteria, occurrence of unacceptable toxicity, decision to withdraw by the doctor or patient, non-compliance, or discontinuation due to administrative reasons. Participants will be monitored throughout the trial period to evaluate the efficacy and safety of the treatment.

Conditions

Colorectal Cancer

Keywords

Colorectal cancer; Immunotherapy; Microsatellite stability; Immune advantage

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  Objective Response Rate (ORR) refers to the proportion of patients who achieve complete response (CR) and partial response (PR) after treatment among the total number of evaluable patients.

  6 months

Secondary Outcomes (4)

• Progression Free Survival

  1 year

• Overall survival

  2 years

• Disease Control Rate

  6 months

• Safety

  6 months

Study Arms (1)

Single-arm experimental group

EXPERIMENTAL

Participants will receive: Aipalolitovorelizumab (QL1706) injection at a dose of 5mg/kg, administered intravenously on Day 1 of each 3-week treatment cycle. Fruquintinib at a dose of 5mg per day, taken orally continuously for the first 2 weeks of each 3-week cycle, followed by 1 week of withdrawal.

Drug: Aipalolitovorelizumab; Drug: Fruquintinib

Interventions

Aipalolitovorelizumab DRUG

Aipalolitovorelizumab (QL1706) injection at a dose of 5mg/kg, administered intravenously on Day 1 of each 3-week treatment cycle.

Single-arm experimental group

Fruquintinib DRUG

Fruquintinib at a dose of 5mg per day, taken orally continuously for the first 2 weeks of each 3-week cycle, followed by 1 week of withdrawal.

Single-arm experimental group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have a full understanding of this study and voluntarily sign the informed consent form;
• Aged 18 - 75 years;
• Patients must be pathologically confirmed as advanced, metastatic or recurrent microsatellite stable (MSS) colorectal cancer (detected by immunohistochemistry, PCR or NGS according to the detection standards of each institutional testing center);
• The results of patients' genetic testing show no POLD1/POLE mutations;
• At least one immune marker is positive:
• PD-L1 CPS score ≥ 10 points, and positive for tumor-infiltrating CD8+ T cells;
• TMB ≥ 10 Muts/mb, and positive for tumor-infiltrating CD8+ T cells; ③ Functional mutations in epigenetic genes such as ARID1A, KMT2A/B/C/D, TET1/2/3, etc., and positive for tumor-infiltrating CD8+ T cells; ④ Presence of positive tertiary lymphoid structures (TLS) in the tumor microenvironment;
• Patients have previously received two or more treatment regimens for advanced or metastatic colorectal cancer, at least one of which includes fluorouracil; or patients have previously received one treatment regimen for advanced or metastatic colorectal cancer and cannot tolerate the second-line standard chemotherapy regimen;
• ECOG performance status of 0 - 1, with no deterioration within 7 days;
• Expected survival ≥ 3 months;
• Organ function levels must meet the following requirements:
• Sufficient bone marrow reserve: absolute neutrophil count ≥ 1.5×10⁹/L, platelet count ≥ 90×10⁹/L, hemoglobin ≥ 9 g/dL; no blood transfusion or use of blood products within 14 days;
• Liver: plasma albumin ≥ 2.8 g/dL; bilirubin ≤ 1.5 times the upper limit of normal (ULN); ALT and AST ≤ 2.5×ULN, and if there is liver metastasis, ALT and AST ≤ 5×ULN; ③ Kidney: serum creatinine ≤ 1.5×ULN;
• Heart: left ventricular ejection fraction (LVEF) ≥ 50%; ⑤ Coagulation: prothrombin time (PT) ≤ 1.5×ULN, international normalized ratio (INR) ≤ 1.5×ULN, activated partial thromboplastin time (APTT) ≤ 1.5×ULN; ⑥ Thyroid-stimulating hormone (TSH) ≤ ULN (if abnormal, FT3 and FT4 levels should be examined simultaneously; if FT3 and FT4 levels are normal, patients can be enrolled);
• Women of childbearing age need to take effective contraceptive measures;

You may not qualify if:

• Unable to comply with the study protocol or research procedures;
• Pregnant or lactating women;
• Any factors affecting oral administration;
• Patients who have previously received immunotherapy and fruquintinib;
• Complicated with any of the following conditions: uncontrolled hypertension, coronary artery disease, arrhythmia, and heart failure;
• Patients who participated in clinical studies of other drugs within 4 weeks before enrollment;
• Alcohol or drug abuse within 4 weeks after the last clinical trial;
• Anti-infective treatment did not stop 14 days before the start of the study;
• Severe uncontrolled systemic diseases, such as severe active infections;
• Urinalysis shows urine protein \> ++, and it is confirmed that 24-hour urine protein \> 1.0 g;
• Active bleeding within 3 months; severe arterial/venous thrombotic events within 6 months; hereditary or acquired bleeding (e.g., coagulation dysfunction); major surgery (except biopsy and electroresection of polyps) within 4 weeks before the study, incompletely healed surgical incisions, or major trauma; use of aspirin (\> 325 mg/day) or current or recent use of dipyridamole, clopidogrel, and cilostazol (10 days before the study);
• Acute myocardial infarction, acute coronary syndrome, or coronary artery bypass grafting within 6 months before the first treatment;
• Use of systemic glucocorticoids or other systemic immunosuppressive drugs within 2 weeks before treatment. Immunosuppressive drugs have been started or are expected to be used during the trial. Physiological replacement doses are allowed for inhaled glucocorticoids;
• Fractures or long-term unhealed wounds;
• Inactivated vaccines 接种 within 4 weeks before enrollment;

Sponsors & Collaborators

• Harbin Medical University: lead

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 Officials

• Yanqiao Zhang

  Harbin Medical University Cancer Hosptital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yanqiao Zhang, PhD

CONTACT

+86 138 4512 0210; yanqiaozhang@ems.hrbmu.edu.cn

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: professor

Study Record Dates

• First Submitted: August 5, 2025
• First Posted: November 17, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: November 17, 2025

Record last verified: 2025-11