NCT05909618
Crizanlizumab Alone or in Combination With Nivolumab for Glioblastoma and Melanoma With Brain Metastases
Recruiting · Phase 2 · Sheba Medical Center · registry updated 2025-07-22
Inclusion and exclusion lines below are quoted from ClinicalTrials.gov. No match score is shown, because a score needs a person's age, biomarkers, and treatment dates. Confirm the record with the study team.
A single-center, open-label, non-randomized phase I/II study to evaluate the efficacy, safety and tolerance of crizanlizumab monotherapy and in combination with nivolumab in patients with advanced glioblastoma (GB) who exhausted standard of care (SOC) therapy, patients with metastatic brain melanoma (MBM) and patients with newly diagnosed unmethylated GB. Subjects will be screened for up to 28 days prior to treatment initiation. Eligible subjects will be allocated to one of 3 cohorts: Cohort 1: Patients with metastatic melanoma with primarily diagnosed or newly progressing brain metastases who failed immunotherapy. Cohort 2: Patients with recurrent or progressing GB following primary radiation therapy and temozolomide. Patients may have failed up to 2 prior systemic treatment lines (including temozolomide as adjuvant therapy) and are candidates for further treatment. Cohort 3: Patients with newly diagnosed GB who were evaluated for methylguanine-DNA methyltransferase(MGMT) methylation status and have un-methylated MGMT promotor-therefore, they are not candidates for maintenance temozolomide therapy.
Inclusion
- Age ≥ 18 years.
- Estimated life expectancy at least 3 months
- Have metastatic melanoma with primarily diagnosed or newly progressing brain metastases.
- Was treated with 1 prior systemic line of immunotherapy - either PD-1 inhibitor monotherapy or combined CTLA4 and PD-1 antibodies or another investigational combination of immunotherapy. Patients with BRAF-mutant melanoma who have also received BRAF mutation targeted therapy are also eligible.
- Have failed prior immunotherapy line, either due to primary resistance or acquired resistance.
- Have measurable disease defined by RECIST criteria and have at least one, non-previously irradiated brain metastasis of at least 1-cm short diameter. Otherwise, previously irradiated lesions should present with enlargement following radiation therapy.
Exclusion
- Systemic steroid therapy for symptomatic brain disease. Note: a dose equivalent to 10 mg prednisone will be allowed
- Have leptomeningeal spread.
- Previous life-threatening toxicity to anti-PD-1 antibody monotherapy.
- Auto-immune disease in the last 2 years requiring systemic immune-suppressive therapy.
- Previous exposure to Crizanlizumab or any other P-selectin inhibitor.
- Previous or current brain hemorrhage.