Crizanlizumab Alone or in Combination With Nivolumab for Glioblastoma and Melanoma With Brain Metastases

Sponsor
Sheba Medical Center
Study ID
NCT05909618
Phase
PHASE2
Status
Recruiting
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Conditions

  • Advanced Glioblastoma
  • MGMT-Unmethylated Glioblastoma
  • Metastatic Melanoma in the Central Nervous System

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

Study Details

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.

Key Dates

Start date
Jul 11, 2023
Status verified
Jul 2025
Primary completion
Jul 30, 2028
Completion
Jul 30, 2030

Study Design

Enrollment
33 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Cohort 1 metastatic melanoma with brain metastases who failed immunotherapy
    The first 3 subjects enrolled to Cohort 1 and Cohort 2 will receive crizanlizumab 5 mg/kg at Cycle 1 Day 1 (C1D1) and C1D15 followed by crizanlizumab 5 mg/kg every 4 weeks until disease progression The subsequent 8 patients will receive crizanlizumab 5 mg/kg at C1D1 and C1D15 followed by 5 mg/kg every 4 weeks plus nivolumab 3mg/kg every 2 weeks until disease progression
  • Experimental: Cohort 2 - Patients with recurrent or progressing GB following radiation and temozolamide.
    The first 3 subjects enrolled to Cohort 1 and Cohort 2 will receive crizanlizumab 5 mg/kg at Cycle 1 Day 1 (C1D1) and C1D15 followed by crizanlizumab 5 mg/kg every 4 weeks until disease progression The subsequent 8 patients will receive crizanlizumab 5 mg/kg at C1D1 and C1D15 followed by 5 mg/kg every 4 weeks plus nivolumab 3mg/kg every 2 weeks until disease progression
  • Experimental: Cohort 3: Patients with newly diagnosed GB
    crizanlizumab starting from 4 weeks after completing radiation therapy. The first 2 subjects will receive crizanlizumab 2.5 mg/kg at C1D1 and C1D15 followed by crizanlizumab 5 mg/kg every 4 weeks. The subsequent 6 subjects will receive crizanlizumab 5 mg/kg at C1D1 and C1D15 followed by crizanlizumab every 4 weeks. Treatment will continue for up to 12 months or until disease progression or unacceptable toxicity.

Primary Outcome Measure

Incidence of treatment-related adverse, serious adverse events, immune-related AEs following treatment with crizanlizumab alone or in combination with nivolumab [ Time Frame: 48 months ]

Central Contacts

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