NCT05909618: 14

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

Recruiting now Phase 2 Last updated 22 July 2025

What this trial tests

Phase 2 trial testing Crizanlizumab-Tmca 10 MG/1 ML Intravenous Solution [ADAKVEO] in Advanced Glioblastoma in 33 participants. Currently enrolling.

Timeline

11 July 2023

Primary endpoint
30 July 2028

30 July 2030

Quick facts

Lead sponsor	Sheba Medical Center
Phase	Phase 2
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	33
Start date	11 July 2023
Primary completion	30 July 2028
Estimated completion	30 July 2030
Sites	1 location across Israel

Drugs / interventions tested

• Crizanlizumab-Tmca 10 MG/1 ML Intravenous Solution [ADAKVEO] — full drug profile →
• Nivolumab 10 MG/1 ML Intravenous Solution [OPDIVO] — full drug profile →

Conditions studied

• Advanced Glioblastoma — all drugs for Advanced Glioblastoma →
• Metastatic Melanoma in the Central Nervous System — all drugs for Metastatic Melanoma in the Central Nervous System →
• MGMT-Unmethylated Glioblastoma — all drugs for MGMT-Unmethylated Glioblastoma →

Sponsor

Sheba Medical Center

Who can join

18 and older, any sex, with Advanced Glioblastoma or Metastatic Melanoma in the Central Nervous System. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Immunotherapeutic Strategies for the Treatment of Glioblastoma: Current Challenges and Future Perspectives.
   Salvato I, Marchini A. · · 2024 · cited 32× · PMID 38610954 · DOI 10.3390/cancers16071276
2. Therapeutic approaches to modulate the immune microenvironment in gliomas.
   Sarantopoulos A, Ene C, Aquilanti E. · · 2024 · cited 19× · PMID 39443641 · DOI 10.1038/s41698-024-00717-4
3. Targeting the dendritic cell-T cell axis to develop effective immunotherapies for glioblastoma.
   Gardam B, Gargett T, Brown MP, Ebert LM. · · 2023 · cited 14× · PMID 37928547 · DOI 10.3389/fimmu.2023.1261257
4. Immune checkpoint inhibitors for glioblastoma: emerging science, clinical advances, and future directions.
   Badani A, Ozair A, Khasraw M, Woodworth GF, et al · · 2025 · cited 12× · PMID 39570554 · DOI 10.1007/s11060-024-04881-2
5. Cancer Organoids as reliable disease models to drive clinical development of novel therapies.
   Blandino G, Satchi-Fainaro R, Tinhofer I, Tonon G, et al · · 2024 · cited 10× · PMID 39731178 · DOI 10.1186/s13046-024-03258-7
6. Targeting the P-selectin/PSGL-1 pathway: discovery of disease-modifying therapeutics for disorders of thromboinflammation.
   Escopy S, Chaikof EL. · · 2024 · cited 8× · PMID 40766814 · DOI 10.1016/j.bvth.2024.100015
7. Barriers to T Cell Functionality in the Glioblastoma Microenvironment.
   Nader NE, Frederico SC, Miller T, Huq S, et al · · 2024 · cited 8× · PMID 39409893 · DOI 10.3390/cancers16193273
8. Immune Checkpoint Inhibitors in Glioblastoma IDHwt Treatment: A Systematic Review.
   Baskaran AB, Kozel OA, Venkatesh O, Wainwright DA, et al · · 2024 · cited 5× · PMID 39766048 · DOI 10.3390/cancers16244148