QL1706 Combined With Standard Therapy for Conversion Therapy of Synchronous Liver Metastases From Colon Cancer: a Multicenter, Single-arm, Exploratory Study

NCT07649473 | Not Yet Recruiting Phase 2

• 1 other identifier: QL-CRC-QIBA-3067
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm clinical study aiming to enroll 30 colon cancer patients with liver-only metastases. All eligible participants will undergo screening and enrollment after signing the informed consent form. All patients will receive stereotactic body radiation therapy (SBRT) targeting 1 to 3 liver lesions (each \< 3 cm) at a total dose of 50 Gy delivered in 5 fractions. For lesions adjacent to the liver capsule, portal vein or bile duct, the target volume can be expanded by 5-10 mm outside the visible lesion boundary. One week after radiotherapy completion, patients will be treated with QL1706 (Apalitamab-Tovorizumab, 5 mg/kg, iv, Q3W) combined with CAPOX plus bevacizumab. Preoperative treatment consists of up to 6 cycles, with each cycle lasting 3 weeks. Efficacy assessment will be conducted every 2 cycles. The investigator or multidisciplinary team (MDT) will decide to initiate curative treatment (surgical resection or radiofrequency ablation of liver metastases, combined with synchronous or staged resection of primary colon lesion) or continue conversion therapy. Surgery shall be scheduled 6 weeks after the final dose of bevacizumab. During the preoperative waiting period, one extra cycle of QL1706 (5 mg/kg, iv, Q3W) plus CAPOX is permitted. The interval between the last immunochemotherapy administration and surgery is required to be 2-3 weeks. Adjuvant therapy is scheduled to start 3 weeks after surgery, and must be initiated no later than 2 months postoperatively. The investigator will determine the use of QL1706 and/or bevacizumab in adjuvant setting according to individual patient conditions. If the time from surgery to adjuvant therapy is less than 4 weeks, the first postoperative cycle will use QL1706 (5 mg/kg, iv, Q3W) combined with CAPOX only. Postoperative QL1706 maintenance treatment will not exceed 1 year. Patients receiving postoperative systemic adjuvant chemotherapy will complete 8 cycles of perioperative CAPOX with or without bevacizumab. Patients with progressive disease (PD) or those who fail conversion therapy within 18 weeks will switch to alternative systemic regimens in accordance with the 2025 guidelines issued by the Chinese Society of Clinical Oncology (CSCO) and the National Comprehensive Cancer Network (NCCN). CAPOX + bevacizumab regimen (repeated every 3 weeks): Oxaliplatin: 130 mg/m², intravenous infusion over 2 hours, d1; Capecitabine: 1000 mg/m² per dose, po, bid, d1-14; Bevacizumab: 7.5 mg/kg, ivgtt, d1.

Conditions

Colon Cancer; Synchronous Liver Metastases

Keywords

QL1706; colon cancer; synchronous liver metastases; conversion

Outcome Measures

Primary Outcomes (1)

• Rate of R0 Resection and Complete Ablation

  The proportion of participants who achieve both R0 resection (no residual tumor at the resection margin) and complete ablation (no evidence of residual ablated disease on imaging) as assessed by postoperative pathology and imaging at 1 month postoperatively.

  1 month postoperatively

Secondary Outcomes (9)

• Conversion Success Rate

  1 month postoperatively

• Objective Response Rate

  6 months after study completion

• Disease Control Rate

  6 months after study completion

• Event Free Survival

  5 years after study completion

• tumor regression grade

  1 month postoperatively

Study Arms (1)

Experimental

EXPERIMENTAL

Patients receive SBRT for 1-3 liver metastases (each lesion \<3 cm) at a dose of 50 Gy in 5 fractions. For lesions adjacent to the liver capsule, portal vein or bile duct, the target volume is expanded by 5-10 mm beyond the visible lesion margin. One week after radiotherapy, patients are treated with QL1706 (Apalitamab-Tovorizumab; 5 mg/kg, iv, Q3W) combined with CAPOX plus bevacizumab. Patients receive up to 6 preoperative 3-week treatment cycles, with efficacy evaluation performed every 2 cycles. The investigator or MDT team decides subsequent management, including curative treatment (surgical resection or radiofrequency ablation of liver metastases with synchronous or staged intestinal lesion resection) or continuous conversion therapy. Surgery is scheduled 6 weeks after the last bevacizumab dose. One additional cycle of QL1706 plus CAPOX may be given during the preoperative waiting period, with a 2-3-week interval between the end of chemoimmunotherapy and surgery.

Drug: QL1706 (Iparomlimab/Tuvonralimab)

Interventions

QL1706 (Iparomlimab/Tuvonralimab) DRUG

Patients receive SBRT for 1-3 liver metastases (each lesion \<3 cm) at a dose of 50 Gy in 5 fractions. For lesions adjacent to the liver capsule, portal vein or bile duct, the target volume is expanded by 5-10 mm beyond the visible lesion margin. One week after radiotherapy, patients are treated with QL1706 (Apalitamab-Tovorizumab; 5 mg/kg, iv, Q3W) combined with CAPOX plus bevacizumab. Patients receive up to 6 preoperative 3-week treatment cycles, with efficacy evaluation performed every 2 cycles. The investigator or MDT team decides subsequent management, including curative treatment (surgical resection or radiofrequency ablation of liver metastases with synchronous or staged intestinal lesion resection) or continuous conversion therapy. Surgery is scheduled 6 weeks after the last bevacizumab dose. One additional cycle of QL1706 plus CAPOX may be given during the preoperative waiting period, with a 2-3-week interval between the end of chemoimmunotherapy and surgery.

Experimental

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 to 70 years, male or female.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Histologically or cytologically confirmed colon adenocarcinoma, with pathologically or radiographically verified liver-only metastases.
• Microsatellite stable (MSS) / proficient mismatch repair (pMMR) confirmed by immunohistochemistry (IHC) or polymerase chain reaction (PCR).
• No prior local or systemic anti-tumor therapy for colon cancer liver metastases, including but not limited to targeted therapy, immunotherapy, systemic or hepatic arterial infusion chemotherapy, radiotherapy and surgery.
• At least one radiographically measurable lesion per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).
• Expected survival of no less than 12 weeks.
• Laboratory test results meet the following criteria within 7 days prior to the first study drug administration (No blood products, hematopoietic growth factors, albumin or other corrective medications deemed necessary by the investigator shall be administered within 14 days before testing):
• Biochemistry: Alkaline phosphatase (ALP), alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 3 × upper limit of normal (ULN), or ≤ 5 × ULN in patients with liver metastases; Total bilirubin (TBIL) ≤ 1.5 × ULN, or ≤ 2 × ULN in patients with liver metastases; Serum creatinine ≤ 1.5 × ULN, or creatinine clearance \> 50 mL/min (calculated via Cockcroft-Gault formula).
• Hematology: Hemoglobin (Hb) ≥ 9.0 g/dL; No red blood cell transfusion within 1 week (including the test day) before baseline Hb test; Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; Platelet count ≥ 100 × 10⁹/L; No platelet transfusion within 1 week (including the test day) before baseline platelet test.
• Coagulation function: International Normalized Ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN. For subjects receiving prophylactic anticoagulation without active bleeding (no bleeding within the past 14 days), INR ≤ 2 × ULN and APTT within normal range.
• Urinalysis: Urinary protein ≤ 30 mg/dL (1+) by dipstick or routine urinalysis. If urine protein ≥ 2+, 24-hour urinary protein quantification shall be less than 1 g/24h.
• No contraindications to radiotherapy, chemotherapy or immunotherapy.
• For female subjects of childbearing potential: serum pregnancy test must be negative within 7 days prior to enrollment. They must agree to use effective contraception throughout the study and for 5 months after the last study drug administration. Male subjects with partners of childbearing potential must also use effective contraception during the study and for 5 months after the last dose. Lactating women are excluded.
• Subjects must be fully informed of the study prior to enrollment, voluntarily sign the written informed consent form, and be willing and able to comply with all scheduled visits, treatment plans, laboratory tests and other study procedures.

You may not qualify if:

• Confirmed non-adenocarcinoma pathological types via histopathology or cytopathology, including squamous cell carcinoma, undifferentiated carcinoma, neuroendocrine carcinoma, etc. For mixed pathological types, eligibility is determined by the predominant component; patients are eligible only if a pathologist confirms the adenocarcinoma component accounts for more than 70%. Patients with primary appendiceal tumors are excluded.
• Presence of distant metastases at sites other than the liver.
• Prior systemic treatment with anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies or other immunotherapeutic agents, or the CAPOX regimen. Prior radiotherapy for liver metastases, or prior radiation exposure to normal liver tissue adjacent to the planned irradiation field.
• History of other malignant tumors within 5 years prior to enrollment, except cured carcinoma in situ of the cervix, basal cell or squamous cell skin cancer, radically treated localized prostate cancer, and radically treated ductal carcinoma in situ.
• Active autoimmune diseases requiring systemic treatment (with immunomodulators, corticosteroids or immunosuppressants) within the past 2 years. Replacement therapies such as thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency are permitted and not regarded as systemic immunosuppressive treatment.
• Immunodeficiency, or receipt of long-term systemic corticosteroids (prednisone equivalent \> 10 mg per day) or other immunosuppressants within 7 days before enrollment or anticipated during study treatment.
• Uncontrolled pleural effusion, pericardial effusion, or moderate to severe ascites.
• Tumor-related complications such as bleeding, perforation or intra-abdominal infection within 3 months prior to enrollment.
• Clinically significant bleeding symptoms or high bleeding risk within 3 months prior to enrollment, including gastrointestinal hemorrhage, gastroesophageal varices, bleeding gastric ulcer, hematochezia, hematemesis or hemoptysis. Presence of gastrointestinal disorders including active peptic ulcer, ulcerative colitis, gastrointestinal perforation, unhealed gastrointestinal fistula, malabsorption syndrome or uncontrolled inflammatory bowel disease.
• Thrombotic or thromboembolic events including cerebrovascular accident, pulmonary embolism and deep vein thrombosis within 6 months prior to enrollment.
• Medical history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonia or interstitial lung disease; or evidence of active pneumonia detected on contrast-enhanced chest CT.
• Any significant clinical or laboratory abnormalities judged by the investigator to compromise safety assessment, including uncontrolled active infection, poorly controlled diabetes, hypertension unresponsive to single-agent therapy, Grade ≥ 2 peripheral neuropathy, congestive heart failure, New York Heart Association (NYHA) Class ≥ II cardiac disease, myocardial infarction within 3 months prior to enrollment, unstable arrhythmia, unstable angina, chronic kidney disease and thyroid dysfunction.
• Major surgery performed within 28 days prior to enrollment without complete postoperative recovery.
• Active infection requiring systemic oral or intravenous treatment within 2 weeks prior to enrollment (excluding viral hepatitis and prophylactic medication).
• Patients with active tuberculosis, or those who received anti-tuberculosis therapy within 1 year prior to enrollment.

Sponsors & Collaborators

• Fujian Medical University: lead

Study Sites (1)

The First Affiliated Hospital of Fujian Medical University

Fuzhou, China

Location

MeSH Terms

Conditions

Colonic Neoplasms

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Xi Shi, MD

CONTACT

+8613960769368; sxi1991@fjmu.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: MD

Study Record Dates

• First Submitted: June 1, 2026
• First Posted: June 16, 2026
• Study Start (Estimated): August 15, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2033
• Last Updated: June 16, 2026

Record last verified: 2026-06

Locations

CN (1)