Phase i study of samalizumab in chronic lymphocytic leukemia and multiple myeloma: Blockade of the immune checkpoint CD200

Daruka Mahadevan, Mark C. Lanasa, Charles Farber, Manjari Pandey, Maria Whelden, Susan J. Faas, Terrie Ulery, Anjli Kukreja, Lan Li, Camille L. Bedrosian, Xiaoping Zhang, Leonard T. Heffner

Producción científica: Articlerevisión exhaustiva

58 Citas (Scopus)

Resumen

Purpose: Samalizumab is a novel recombinant humanized monoclonal antibody that targets CD200, an immunoregulatory cell surface member of the immunoglobulin superfamily that dampens excessive immune responses and maintains self-tolerance. This first-in-human study investigated the therapeutic use of samalizumab as a CD200 immune checkpoint inhibitor in chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). Experimental design: Twenty-three patients with advanced CLL and 3 patients with MM were enrolled in an open-label phase 1 study (NCT00648739). Patients were assigned sequentially to one of 7 dose level cohorts (50 to 600 mg/m2) in a 3 + 3 study design, receiving a single dose of samalizumab intravenously once every 28 days. Primary endpoints were safety, identification of the maximum tolerated dose (MTD), and pharmacokinetics. Secondary endpoints were samalizumab binding to CD200, pharmacodynamic effects on circulating tumor cells and leukocyte subsets, and clinical responses. Results: Twenty-one patients received > 1 treatment cycle. Adverse events (AEs) were generally mild to moderate in severity. Samalizumab produced dose-dependent decreases in CD200 expression on CLL cells and decreased frequencies of circulating CD200 + CD4+ T cells that were sustained at higher doses. The MTD was not reached. Decreased tumor burden was observed in 14 CLL patients. One CLL patient achieved a durable partial response and 16 patients had stable disease. All MM patients had disease progression. Conclusions: Samalizumab had a good safety profile and treatment was associated with reduced tumor burden in a majority of patients with advanced CLL. These preliminary positive results support further development of samalizumab as an immune checkpoint inhibitor. Trial registration: ClinicalTrials.gov, NCT00648739 registered April 1, 2008.

Idioma originalEnglish (US)
Número de artículo227
PublicaciónJournal for ImmunoTherapy of Cancer
Volumen7
N.º1
DOI
EstadoPublished - ago 23 2019
Publicado de forma externa

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research
  • Immunology and Allergy
  • Pharmacology
  • Immunology

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