Ivonescimab Plus Chemotherapy in Patients with Initially Unresectable Colorectal Cancer Liver Metastases

Launched by CANCER INSTITUTE AND HOSPITAL, CHINESE ACADEMY OF MEDICAL SCIENCES · Feb 22, 2025

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment for patients with colorectal cancer that has spread to the liver and cannot be completely removed by surgery. The treatment being tested is a combination of a drug called ivonescimab and chemotherapy. The main goals of the trial are to see if this combination helps shrink the tumors and to monitor any side effects that patients may experience while receiving the treatment.

To participate in this study, you must be at least 18 years old and have been diagnosed with specific types of colorectal cancer that have spread only to the liver. You also need to have measurable liver tumors that doctors believe cannot be surgically removed. Participants will receive ivonescimab and chemotherapy every three weeks for up to eight cycles. During this time, they will visit the clinic every six weeks for check-ups and tests to monitor their progress. If the treatment is working well, some participants may be able to have surgery to remove the tumors later on. This trial is currently looking for new participants, and it aims to provide valuable information about the effectiveness and safety of this treatment option.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Age ≥18 years.
• • 2. Histologically confirmed colorectal adenocarcinoma.
• • 3. Radiologically confirmed liver-only metastases. Patients with ≤1 cm extrahepatic lesions not confirmed as metastatic are eligible.
• • 4. No prior systemic therapy or local therapy for metastatic lesions, or completion of neoadjuvant/adjuvant chemotherapy ≥6 months before diagnosed disease recurrence.
• • 5. Liver metastases considered unresectable or borderline resectable by multidisciplinary evaluation.
• • 6. Liver metastases were measurable according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• • 7. Eastern Cooperative Oncology Group performance status 0-1
• • 8. Life expectancy ≥12 weeks.
• • 9. No contraindications to hepatic resection/ablation, and primary tumor resectable or previously resected.
• • 10. Adequate organ function as determined by normal bone marrow function (hemoglobin ≥80 g/L, absolute neutrophil count ≥1.5×10⁹/L, and platelets ≥100×10⁹/L), renal function (serum creatinine ≤1.5×upper limit of normal \[ULN\] and creatinine clearance ≥30 mL/min), liver function (serum bilirubin ≤2×ULN and serum transaminases ≤5×ULN).
• Exclusion Criteria:
• • 1. Definite extrahepatic metastases.
• • 2. dMMR or MSI-H colorectal cancer.
• • 3. Intolerance to the study drug during prior neoadjuvant/adjuvant therapy.
• • 4. Toxicities from prior therapy have not resolved to ≤ Grade 1 (according to NCI-CTCAE v5.0), except for alopecia (any grade) and peripheral neuropathy (≤ Grade 2).
• • 5. History of or concurrent other malignancies within the past 5 years, except cured localized tumors.
• • 6. Surgery performed within 28 days prior to enrollment.
• • 7. Hypertension with systolic blood pressure ≥160mmHg or diastolic blood pressure ≥100mmHg despite antihypertensive treatment.
• • 8. Major cardiovascular events within 12 months prior to enrollment.
• • 9. History of severe bleeding tendency or coagulation disorders; tumor encasement of major blood vessels or significant necrosis or cavitation, and the investigator deems participation in the study may pose a bleeding risk.
• • 10. Active autoimmune disease requiring systemic treatment within the past 2 years.
• • 11. History of immunodeficiency, positive HIV antibody test, or long-term use of corticosteroids or other immunosuppressants.
• • 12. Prior history of allogeneic bone marrow or organ transplantation.
• • 13. Received live vaccines within 30 days prior to the first dose or plans to receive live vaccines during the study period.
• • 14. Allergy to any component of the study drugs; history of severe hypersensitivity reactions to other monoclonal antibodies.
• • 15. Women who are pregnant or breastfeeding.
• • 16. Severe comorbidities or any other condition that precludes safe administration of the study treatment, including but not limited to symptomatic congestive heart failure (Class II or higher per NYHA classification), unstable angina, acute myocardial ischemia, poorly controlled arrhythmias, decompensated cirrhosis, nephrotic syndrome, uncontrolled metabolic disorders, severe active peptic ulcer disease or gastritis, or psychiatric/social conditions that may limit compliance with study requirements or impair the subject's ability to provide written informed consent.
• • 17. Any other condition deemed by the investigator as unsuitable for participation in this study.