Brain metastasis represents one of the worst prognostic outcomes in advanced malignant tumors. Approximately 10% to 40% of patients with solid tumors develop brain metastases, a incidence rate significantly higher than that of primary malignant brain tumors. Over 80% of patients present with multiple brain metastases at diagnosis, often precluding surgical intervention.
Brain metastases typically occur in the late stages of cancer. Patients have often received multiple prior therapies and developed resistance to first- and second-line drugs, leaving limited pharmacological options. The rapid growth of intracranial tumors poses an immediate threat to life. Consequently, radiotherapy and surgery currently form the cornerstone of clinical management for these patients. Thus, developing effective systemic therapies is an urgent and unmet medical need .
Utidelone, a new-generation epothilone anticancer agent, has demonstrated good efficacy and safety. Previous studies indicate that utidelone achieves higher concentrations in most tissues, including the brain, compared to plasma, suggesting its ability to readily cross the blood-brain barrier . Furthermore, a Phase III clinical trial in metastatic breast cancer showed that utidelone in combination with capecitabine significantly improved the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) compared to capecitabine alone in patients previously treated with anthracyclines and taxanes .
A separate Phase II study demonstrated that bevacizumab combined with carboplatin achieved a central nervous system objective response rate (CNS ORR) of 63%, with a median PFS of 5.62 months and a median OS of 14.1 months in breast cancer patients with brain metastases . Regarding safety, utidelone has a relatively low incidence of adverse reactions aside from peripheral neurotoxicity .
Based on this evidence, this proposed study aims to evaluate the efficacy and safety of utidelone and bevacizumab, combined with etoposide for breast cancer cohorts or without etoposide for lung cancer cohorts, in patients with malignant tumor brain metastases.
Subjects must provide informed consent for the trial and voluntarily sign the written informed consent form (ICF) prior to the study.
Aged 18-75 years, male or female.
Patients with histologically or cytologically confirmed non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC):The pathological type of NSCLC must be adenocarcinoma.For advanced NSCLC patients with positive EGFR sensitive mutations, ALK fusion, ROS1 fusion, RET fusion, BRAF V600E, or NTRK fusion mutations, they must have experienced disease progression after adequate targeted therapy for the corresponding mutation AND after at least one platinum-based chemotherapy regimen, or be intolerant to platinum-based therapy.Patients with NSCLC without driver gene mutations and patients with SCLC must have experienced disease progression after platinum-based chemotherapy with or without PD-1/PD-L1 inhibitors, or be intolerant to the aforementioned therapy.
Eastern Cooperative Oncology Group (ECOG) performance status (PS) score: 0-2.
History of other malignancies (including primary brain or leptomeningeal tumors) within the past 5 years, except for cured basal cell skin carcinoma or cervical carcinoma in situ.
Prior use of Utidelone injection or Bevacizumab.
Imaging shows tumor invasion of major blood vessels, unclear demarcation from vessels, or judged by the investigator as having a high probability of fatal massive hemorrhage due to tumor invasion of important vessels during the study (major thoracic vessels include the thoracic aorta, left pulmonary artery, right pulmonary artery, 4 pulmonary veins, superior vena cava, inferior vena cava, and aorta).
Major organ surgery (excluding needle biopsy) or significant trauma within 4 weeks prior to the first dose of study drug, or scheduled elective surgery during the trial period.
Tianjin Medical University Cancer Institute and Hospital
Lead sponsor
Beijing Baiyang Zhihe Medical Technology Transfer Services Co., Ltd.
Collaborator
Innovent Biologics (Suzhou) Co. Ltd.
Collaborator