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

Official title

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

Overview

The goal of this clinical trial is to learn if ivonescimab plus chemotherapy works to treat colorectal cancer liver metastases that cannot be completely removed. It will also learn about the safety of ivonescimab. The main questions it aims to answer are: Does ivonescimab plus chemotherapy raise the objective response rate? What medical problems do participants have when receiving ivonescimab plus chemotherapy? Participants will: Receive ivonescimab and chemotherapy every 3 weeks, no more than 8 cycles. Visit the clinic once every 2 cycles (6 weeks) for checkups and tests. Receive curative surgery, maintenance therapy, or discontinue study treatment according to the expert team's evaluation.

Interventions

• Drug Ivonescimab plus chemotherapy
  Ivonescimab, 20mg/kg, D1, Q3W; Oxaliplatin, 130mg/m2, D1, Q3W; Capecitabine, 1000mg/m2, BID, D1-D14, Q3W

Primary outcome measures

• Objective Response Rate [Time frame: At the end of Cycle 8 (each cycle is 21 days)]
• Treatment-Emergent Adverse Events [Time frame: From the date of enrollment until 90 days after the Cycle 8 (each cycle is 21 days)]

Secondary outcome measures (7)

• No evidence of disease rate [Time frame: 6 months]
• Progression-free survival [Time frame: From date of enrollment until the date of first documented progression, assessed up to 2 years]
• Overall Survival [Time frame: From date of enrollment until the date of death, assessed up to 2 years]
• Recurrence-free survival [Time frame: From the date of curative resection until the date of first documented progression, assessed up to 2 years]
• Disease control rate [Time frame: At the end of Cycle 8 (each cycle is 21 days)]
• Treatment-related adverse events [Time frame: From the date of enrollment until 90 days after the Cycle 8 (each cycle is 21 days)]
• Immunotherapy-related adverse events [Time frame: From the date of enrollment until 180 days after the Cycle 8 (each cycle is 21 days)]

Eligibility criteria

Inclusion criteria

• Age ≥18 years.
• Histologically confirmed colorectal adenocarcinoma.
• Radiologically confirmed liver-only metastases. Patients with ≤1 cm extrahepatic lesions not confirmed as metastatic are eligible.
• No prior systemic therapy or local therapy for metastatic lesions, or completion of neoadjuvant/adjuvant chemotherapy ≥6 months before diagnosed disease recurrence.
• Liver metastases considered unresectable or borderline resectable by multidisciplinary evaluation.
• Liver metastases were measurable according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• Eastern Cooperative Oncology Group performance status 0-1
• Life expectancy ≥12 weeks.
• No contraindications to hepatic resection/ablation, and primary tumor resectable or previously resected.
• 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

• Definite extrahepatic metastases.
• dMMR or MSI-H colorectal cancer.
• Intolerance to the study drug during prior neoadjuvant/adjuvant therapy.
• 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).
• History of or concurrent other malignancies within the past 5 years, except cured localized tumors.
• Surgery performed within 28 days prior to enrollment.
• Hypertension with systolic blood pressure ≥160mmHg or diastolic blood pressure ≥100mmHg despite antihypertensive treatment.
• Major cardiovascular events within 12 months prior to enrollment.
• 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.
• Active autoimmune disease requiring systemic treatment within the past 2 years.
• History of immunodeficiency, positive HIV antibody test, or long-term use of corticosteroids or other immunosuppressants.
• Prior history of allogeneic bone marrow or organ transplantation.
• Received live vaccines within 30 days prior to the first dose or plans to receive live vaccines during the study period.
• Allergy to any component of the study drugs; history of severe hypersensitivity reactions to other monoclonal antibodies.
• Women who are pregnant or breastfeeding.
• 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.
• Any other condition deemed by the investigator as unsuitable for participation in this study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Uni — Beijing

Identifiers

NCT: NCT06848842 · NCC5043

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗