A Single-arm, Single-center, Phase II Clinical Study of Aipalolitovorelizumab (QL1706) Combined With Bevacizumab and Standard Chemotherapy as First-line Treatment for MSS/pMMR Metastatic Colorectal Cancer With BRAF V600E Mutation

NCT07229846 | Not Yet Recruiting Phase 2

• 1 other identifier: QL-CRC-QIBA-3006
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, single-arm, single-center phase II clinical study, aiming to investigate the safety and efficacy of Aipalolitovorelizumab (QL1706) combined with bevacizumab plus standard chemotherapy regimen as first-line treatment for patients with MSS/pMMR metastatic colorectal cancer harboring BRAF V600E mutation. Patients will receive intravenous administration of Aipalolitovorelizumab (QL1706) injection + bevacizumab + oxaliplatin/irinotecan/fluorouracil/calcium folinate, along with oral capecitabine. After completing the corresponding treatment cycles, patients will enter the maintenance treatment phase as determined by the researcher. In the maintenance treatment phase, a 3-week treatment regimen of Aipalolitovorelizumab (QL1706) injection combined with bevacizumab and capecitabine will be adopted, with the administration method and dosage remaining unchanged. The primary endpoint of this study is objective response rate (ORR); the secondary endpoints include progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response (DOR), and safety.

Conditions

Colorectal Cancer

Keywords

Colorectal cancer; BRAF V600E mutation; Microsatellite stability; Immunotherapy; First-line treatment

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  Defined as the proportion of patients who achieved complete response (CR) andpartial response (PR) according to RECIST v1.1.

  6 months

Secondary Outcomes (5)

• Progression Free Survival

  1 year

• Disease Control Rate

  6 months

• Duration of Response

  6 months

• Overall survival

  2 years

• Safety

  6 months

Study Arms (1)

Single-arm experimental group

EXPERIMENTAL

Drug: Aipalolitovorelizumab; Drug: XELOX + Bevacizumab; Drug: mFOLFOX + Bevacizumab; Drug: FOLFOXIRI + Bevacizumab; Drug: Oxaliplatin + Irinotecan + Capecitabine + Bevacizumab

Interventions

Aipalolitovorelizumab DRUG

Aipalolitovorelizumab (QL1706) Injection: 5 mg/kg, intravenous infusion (ivgtt), d1, Q3W;

Single-arm experimental group

XELOX + Bevacizumab DRUG

Bevacizumab 7.5 mg/kg, intravenous infusion, Day 1; Oxaliplatin 130 mg/㎡, intravenous infusion over 2 hours, Day 1; Capecitabine 1000 mg/㎡, oral administration (po), twice a day (bid), Days 1-14. Repeat every 3 weeks.

Single-arm experimental group

mFOLFOX + Bevacizumab DRUG

Bevacizumab 5 mg/kg, intravenous infusion, Day 1; Oxaliplatin 85 mg/㎡, intravenous infusion over 2 hours, Day 1; Calcium Folinate 400 mg/m², intravenous infusion over 2 hours, Day 1; Fluorouracil 400 mg/m², intravenous bolus, Day 1, followed by 1200 mg/(m²·d) continuous intravenous infusion for 2 days (total dose 2400 mg/m², infusion over 46-48 hours). Repeat every 2 weeks.

Single-arm experimental group

FOLFOXIRI + Bevacizumab DRUG

Bevacizumab 5 mg/kg, intravenous infusion, Day 1; Irinotecan 165 mg/m², intravenous infusion, Day 1; Oxaliplatin 85 mg/m², intravenous infusion, Day 1; Calcium Folinate 400 mg/m², intravenous infusion, Day 1; Fluorouracil with a total dose of 2400-3200 mg/m², continuous intravenous infusion over 48 hours on Day 1. Repeat every 2 weeks.

Single-arm experimental group

Oxaliplatin + Irinotecan + Capecitabine + Bevacizumab DRUG

Bevacizumab 7.5 mg/kg, intravenous infusion, Day 1; Oxaliplatin 130 mg/㎡, intravenous infusion over 2 hours, Day 1; Irinotecan 180 mg/m², intravenous infusion over 30-90 minutes, Day 1; Capecitabine 1000 mg/㎡, oral administration (po), twice a day (bid), Days 1-14. Repeat every 3 weeks.

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:

• Aged 18-75 years (inclusive of 18 and 75 years) at the time of signing the ICF, male or female;
• Patients with histopathologically confirmed unresectable metastatic colorectal adenocarcinoma of MSS/pMMR type with known BRAF V600E mutation;
• Expected survival period ≥ 12 weeks;
• For subjects who have received neoadjuvant/adjuvant therapy previously, the time from the last treatment to recurrence or progression must exceed 6 months;
• Adverse events (AEs) related to previous treatment have recovered to grade ≤ 1 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) (except for alopecia);
• According to the RECIST version 1.1 criteria, the researcher assesses that there is at least one measurable lesion, which should not have received local treatment such as radiotherapy (lesions located in the previously irradiated area can also be regarded as eligible measurable lesions if progression is confirmed);
• Routine blood tests: No blood transfusion or use of blood products within 14 days. White blood cell count \> 3000/µl, absolute neutrophil count (ANC) ≥ 1500 cells/µl, platelet count ≥ 75,000/µl, hemoglobin ≥ 9.0 g/dL, left ventricular ejection fraction (LVEF) ≥ 50%, Fridericia-corrected QT interval (QTcF) \< 470 milliseconds, activated partial thromboplastin time (APTT) ≤ 1.5 times the upper limit of normal (ULN);
• Bilirubin ≤ 1.5 times ULN, ALT and AST ≤ 2.5 times ULN; if there is liver metastasis, ALT and AST ≤ 5 times ULN, total bilirubin (TBLL) ≤ 3 times ULN; creatinine \< 1.5 times ULN;
• ECOG PS score of 0-1 within 7 days before the first administration of the study drug;
• Hepatitis B surface antigen (HBsAg) (-) and hepatitis B core antibody (HBcAb) (-), and no active hepatitis is clinically determined. If HBsAg (+) or HBcAb (+), then hepatitis B virus deoxyribonucleic acid (HBV-DNA) must be \< 1000 copies/mL or 200 IU/mL (if the lower limit of detection in the research unit is \> 200 IU/mL, subjects with results below the lower limit of detection can be enrolled);
• Hepatitis C virus (HCV) antibody (-); if HCV antibody (+), HCV-RNA test must be negative for enrollment. Subjects with co-infection of hepatitis B and hepatitis C must be excluded (HBsAg or HBcAb positive, and HCV antibody positive);
• For female subjects of childbearing potential, the blood pregnancy test within 7 days before the first drug administration must be negative. Female subjects of childbearing potential and male subjects whose partners are women of childbearing age need to use at least one medically recognized contraceptive method (such as intrauterine device, contraceptives, or condoms) during the study treatment period and until at least 3 months after the last use of Aipalolitovorelizumab (QL1706) and bevacizumab, and at least 6 months after the last use of chemotherapy (whichever occurs later);
• Provide a signed ICF and be willing to comply with all research procedures and rules specified in the protocol;
• Have good compliance and be cooperative with follow-up.

You may not qualify if:

• Have other active malignant tumors within 5 years before the first administration of the study drug. Patients with cured localized tumors such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the prostate, carcinoma in situ of the cervix, and carcinoma in situ of the breast can be enrolled;
• Have central nervous system (CNS) or leptomeningeal metastasis;
• Have received radiotherapy within 6 months before the start of study treatment; except for palliative radiotherapy for bone lesions performed more than 14 days before the start of study treatment; radiotherapy covering more than 30% of the bone marrow area within 28 days before the first administration is not allowed;
• Have previously received treatment with targeted drugs against EGFR or VEGF/vascular endothelial growth factor receptor (VEGFR) targets (including bevacizumab, cetuximab, panitumumab, aflibercept, regorafenib, or biosimilars of the above drugs, etc.);
• Have previously received any T-cell co-stimulation or immune checkpoint inhibitor therapy, including but not limited to CTLA-4 inhibitors, PD-1 inhibitors, PD-L1/2 inhibitors, or other T-cell-targeted drugs;
• Have a known history of severe allergy to any study drug analogs or study drug excipients;
• Pleural effusion, pericardial effusion that cannot be controlled by appropriate intervention, or ascites that requires frequent drainage;
• Have had cerebrovascular accident, myocardial infarction, unstable angina, or poorly controlled arrhythmia (including QTc interval ≥ 450 ms in males and ≥ 470 ms in females) within half a year (QTc interval is calculated by Fridericia formula);
• Have New York Heart Association (NYHA) class III or IV cardiac insufficiency, or echocardiography shows left ventricular ejection fraction (LVEF) \< 50%;
• Have a history of immunodeficiency, including positive human immunodeficiency virus (HIV) antibody test, or have other acquired or congenital immunodeficiency diseases, or have a history of organ transplantation and allogeneic bone marrow transplantation;
• Have active pulmonary tuberculosis;
• Patients with past or current interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, severe impairment of pulmonary function, etc., which may interfere with the detection and treatment of suspected drug-related pulmonary toxicity;
• Have active autoimmune diseases or a history of autoimmune diseases (such as interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes). Except for the following subjects: patients with vitiligo or cured childhood asthma/allergies who do not need any intervention in adulthood; patients with autoimmune-mediated hypothyroidism treated with a stable dose of thyroid replacement hormone; type I diabetes mellitus using a stable dose of insulin;
• Have received live attenuated vaccine treatment within 28 days before the first administration of the study drug;
• Subjects who need continuous systemic treatment (\> 7 days) with corticosteroids (\> 10 mg/day prednisone or equivalent dose of similar drugs) or other immunosuppressants within 14 days before the first administration of the study drug or during the study period. In the absence of active autoimmune diseases, inhalation or topical use of steroids, or adrenal hormone replacement with a dose ≤ 10 mg/day prednisone equivalent dose is allowed;

Sponsors & Collaborators

• Yanqiao Zhang: lead

Study Sites (1)

Harbin Medical University Cancer Hosptital

Harbin, China

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

XELOX; Bevacizumab; Oxaliplatin; Irinotecan; Capecitabine

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Camptothecin; Alkaloids; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

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: SPONSOR INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: August 5, 2025
• First Posted: November 17, 2025
• Study Start: February 1, 2026
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2028
• Last Updated: January 8, 2026

Record last verified: 2026-01

Locations

CN (1)