Phase Ib/II Study of QL1706 + Fruquintinib + SCRT vs. Standard Third-Line Therapy in Unresectable Liver-Metastatic pMMR/MSS Colorectal Cancer: Safety, Tolerability, and Efficacy.

NCT07353268 | Not Yet Recruiting Phase 2

• 1 other identifier: ZLK20250622
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to evaluate the safety, tolerability, and efficacy of Epalolitovoreli Monoclonal Antibody (QL1706) combined with Fruquintinib and Short-Course Radiotherapy (SCRT), compared with standard third-line therapy, in the treatment of patients with unresectable liver-metastatic pMMR/MSS colorectal cancer.

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival（PFS）

  Progression-free survival (PFS) is defined as the time from the initiation of study treatment to the first occurrence of disease progression or death from any cause, whichever comes first.

  an expected average of 6 months

Secondary Outcomes (2)

• Overall Survival

  an expected average of 5 years

• dverse events (AEs) were graded according to the NCI CTCAE version 5·0

  an expected average of 1.5 years

Study Arms (2)

QL1706 + Fruquintinib + Short-Course Ablative Radiotherapy (SCART)

EXPERIMENTAL

Patients will receive the PD-1/CTLA-4 bispecific antibody Epalolitovoreli Monoclonal Antibody (QL1706) at a dose of 5 mg/kg by intravenous infusion every 3 weeks (Q3W). Patients will concomitantly receive oral Fruquintinib once daily (QD). The dose will be determined in a Phase Ib dose-escalation phase exploring 3 mg and 4 mg QD levels, using a modified 3+3 design to establish the Recommended Phase II Dose (RP2D). Patients will undergo Short-Course Ablative Radiotherapy (SCART) to the liver metastasis/metastases. The prescribed dose is 15 Gy in 3 fractions to the Gross Tumor Volume (GTV) and 45-72 Gy in 3 fractions to the Subclinical Target Volume (STV). Treatment with QL1706 and Fruquintinib will continue until disease progression, unacceptable toxicity, or other protocol-specified discontinuation criteria.

Drug: QL1706 + Fruquintinib + Short-Course Ablative Radiotherapy (SCART)

Standard Third-Line Therapy

ACTIVE COMPARATOR

Patients will receive one of the following standard-of-care third-line therapies for metastatic colorectal cancer, selected by the investigator based on the patient's prior treatment history and comprehensive condition: Cetuximab with or without Irinotecan (for patients not previously treated with cetuximab). Regorafenib. Fruquintinib. Trifluridine/Tipiracil (TAS-102) with or without Bevacizumab.

Drug: Standard Third-Line Therapy

Interventions

QL1706 + Fruquintinib + Short-Course Ablative Radiotherapy (SCART) DRUG

Patients will receive the PD-1/CTLA-4 bispecific antibody Epalolitovoreli Monoclonal Antibody (QL1706) at a dose of 5 mg/kg by intravenous infusion every 3 weeks (Q3W). Patients will concomitantly receive oral Fruquintinib once daily (QD). The dose will be determined in a Phase Ib dose-escalation phase exploring 3 mg and 4 mg QD levels, using a modified 3+3 design to establish the Recommended Phase II Dose (RP2D). Patients will undergo Short-Course Ablative Radiotherapy (SCART) to the liver metastasis/metastases. The prescribed dose is 15 Gy in 3 fractions to the Gross Tumor Volume (GTV) and 45-72 Gy in 3 fractions to the Subclinical Target Volume (STV). Treatment with QL1706 and Fruquintinib will continue until disease progression, unacceptable toxicity, or other protocol-specified discontinuation criteria.

QL1706 + Fruquintinib + Short-Course Ablative Radiotherapy (SCART)

Standard Third-Line Therapy DRUG

Patients will receive one of the following standard-of-care third-line therapies for metastatic colorectal cancer, selected by the investigator based on the patient's prior treatment history and comprehensive condition: Cetuximab with or without Irinotecan (for patients not previously treated with cetuximab). Regorafenib. Fruquintinib. Trifluridine/Tipiracil (TAS-102) with or without Bevacizumab.

Standard Third-Line Therapy

Eligibility Criteria

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

You may qualify if:

• Signed written informed consent, and ability to comply with the scheduled visits and related procedures as specified in the protocol.
• Age ≥18 years and ≤75 years, male or female.
• Histologically or cytologically confirmed metastatic colorectal cancer with unresectable liver metastasis(es) measuring ≥5 cm in the longest diameter.
• Confirmed pMMR (proficient mismatch repair) or MSS (microsatellite stable) status by immunohistochemistry (IHC), next-generation sequencing (NGS), or PCR testing.
• Disease progression after, intolerance to, lack of access to, or refusal of standard second-line therapy.
• Baseline\* hematologic tests (within 7 days prior to the first dose of study drug) meeting the following criteria:
• Hemoglobin ≥90 g/L.
• Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L.
• Platelet count ≥100 × 10⁹/L.
• Eosinophil count ≤1.5 × Upper Limit of Normal (ULN).
• Baseline serum biochemical tests (within 7 days prior to the first dose) meeting the following criteria:
• Total bilirubin ≤1.5 × ULN (if total bilirubin \>1.5 × ULN but direct bilirubin ≤ ULN, enrollment is permitted).
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤3 × ULN.
• Serum creatinine ≤1.5 × ULN or creatinine clearance (CCr) ≥45 mL/min (calculated using the Cockcroft-Gault formula with actual body weight).
• Albumin ≥30 g/L.

You may not qualify if:

• \. History of allergy to any study drug, including Epalolitovoreli Monoclonal Antibody and Fruquintinib.
• \. Pregnant or breastfeeding women, or women planning to become pregnant within 6 months before, during, or after the last dose of study drug.
• \. Known history of active seizures, active central nervous system metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal metastases; newly diagnosed brain or leptomeningeal metastases.
• \. Cardiovascular or cerebrovascular diseases with significant clinical implications, including:
• Ventricular arrhythmias or other uncontrolled arrhythmias requiring medical intervention (e.g., antiarrhythmic medication).
• Severe conduction disorders (e.g., third-degree atrioventricular block).
• Heart rate-corrected QT interval (QTc, calculated using Fridericia's formula) ≥480 ms.
• Uncontrolled hypertension (systolic blood pressure \>160 mmHg and/or diastolic blood pressure \>100 mmHg), history of hypertensive crisis or hypertensive encephalopathy.
• History of myocarditis.
• Current congestive heart failure requiring treatment.
• New York Heart Association (NYHA) Class III or IV cardiovascular disease.
• Acute coronary syndrome (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to the first dose.
• Cerebrovascular accident or transient ischemic attack within 6 months prior to the first dose.
• Interstitial lung disease, pulmonary fibrosis, pneumoconiosis, drug-related pneumonia, radiation pneumonitis requiring steroid or other treatment, severe pulmonary dysfunction, or history of other forms of restrictive lung disease.
• \. History of allergic constitution, asthma, or atopic dermatitis. 6. Patients with massive pleural effusion or massive ascites. 7. Active autoimmune disease requiring systemic treatment (e.g., disease-modifying drugs, corticosteroids, or immunosuppressants) within 2 years prior to the first dose. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement for adrenal or pituitary insufficiency) is not considered systemic treatment.

Sponsors & Collaborators

• Tao Zhang: lead

Study Sites (1)

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, China

Location

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

• Tao Zhang, MD

  Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhenyu Lin, MD

CONTACT

027-83262683; whxhlzy@hust.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: January 13, 2026
• First Posted: January 20, 2026
• Study Start: January 21, 2026
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: January 20, 2026

Record last verified: 2026-01

Locations

CN (1)