2. Academic Validation
  3. Phase I study of samalizumab in chronic lymphocytic leukemia and multiple myeloma: blockade of the immune checkpoint CD200

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

  • J Immunother Cancer. 2019 Aug 23;7(1):227. doi: 10.1186/s40425-019-0710-1.
Daruka Mahadevan 1,  Mark C Lanasa 2,  Charles Farber 3,  Manjari Pandey 4,  Maria Whelden 5,  Susan J Faas 5,  Terrie Ulery 5,  Anjli Kukreja 5,  Lan Li 5,  Camille L Bedrosian 5,  Xiaoping Zhang 5,  Leonard T Heffner 6
Affiliations

Affiliations

  • 1 Department of Medicine Division of Hematology/Oncology, University of Arizona Cancer Center, 1515. N. Campbell Avenue, Room 1905, Tucson, AZ, 85724, USA. [email protected].
  • 2 Duke University Medical Center, Durham, NC, USA.
  • 3 Summit Medical Center, MD Anderson Cancer Center, Morristown, NJ, USA.
  • 4 The West Cancer Center, University of Tennessee, Memphis, TN, USA.
  • 5 Alexion Pharmaceuticals, Inc., New Haven, CT, USA.
  • 6 Winship Cancer Institute of Emory University, Atlanta, GA, USA.
PMID: 31443741 DOI: 10.1186/s40425-019-0710-1
Abstract

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.

Keywords

CD200; CLL; Immune checkpoint inhibitor; Multiple myeloma; Samalizumab.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-P99400
    99.81%, Anti-CD200 Antibody