Combining ivonescimab with chemotherapy for treating colorectal cancer liver metastases

A Phase II Clinical Study of Ivonescimab Plus CAPOX Regimen in Patients With Initially Unresectable Colorectal Cancer Liver-only Metastases

This study is testing if adding ivonescimab to chemotherapy can help people with colorectal cancer that has spread to the liver feel better and improve their treatment results.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences (Academic / other)
• Drugs / interventions: chemotherapy, ivonescimab
• Locations: 1 site (Beijing)
• Trial ID: NCT06848842 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness of ivonescimab in combination with chemotherapy for patients with initially unresectable colorectal cancer liver metastases. Participants will receive the treatment every three weeks for up to eight cycles, with regular clinic visits for monitoring and assessments. The study will focus on measuring the objective response rate and assessing the safety profile of the treatment. The ultimate goal is to determine if this combination can improve treatment outcomes for these patients.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with histologically confirmed colorectal adenocarcinoma and liver-only metastases deemed unresectable or borderline resectable.

Not a fit: Patients with resectable liver metastases or those who have received prior systemic or local therapy for metastatic lesions may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve response rates and overall outcomes for patients with colorectal cancer liver metastases.

How similar studies have performed: While the combination of immunotherapy and chemotherapy is being explored in various cancers, this specific approach with ivonescimab is novel and has not been extensively tested in this context.

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.

Where this trial is running

Beijing

• National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College — Beijing, China (Recruiting)

Study contacts

• Study coordinator: Lin Yang

Conditions Colorectal Liver Metastases; initially unresectable; ivonescimab; objective response rate