title: SAR3419: an anti-CD19-Maytansinoid Immunoconjugate for the treatment of B-cell malignancies.
abstract: SAR3419 is a novel anti-CD19 humanized monoclonal antibody conjugated to a maytansine derivate through a cleavable linker for the treatment of B-cell malignancies. SAR3419 combines the strengths of a high-potency tubulin inhibitor and the exquisite B-cell selectivity of an anti-CD19 antibody. The internalization and processing of SAR3419, following its binding at the surface of CD19-positive human lymphoma cell lines and xenograft models, release active metabolites that trigger cell-cycle arrest and apoptosis, leading to cell death and tumor regression. SAR3419 has also been shown to be active in different lymphoma xenograft models, including aggressive diffuse large B-cell lymphoma, resulting in complete regressions and tumor-free survival. In these models, the activity of SAR3419 compared favorably with rituximab and lymphoma standard of care chemotherapy. Two phase I trials with 2 different schedules of SAR3419 as a single agent were conducted in refractory/relapsed B-cell non-Hodgkin lymphoma. Activity was reported in both schedules, in heavily pretreated patients of both follicular and diffuse large B-cell lymphoma subtypes, with a notable lack of significant hematological toxicity, validating SAR3419 as an effective antibody-drug conjugate and opening opportunities in the future. Numerous B-cell-specific anti-CD19 biologics are available to treat B-cell non-Hodgkin lymphoma, and early phase I results obtained with SAR3419 suggest that it is a promising candidate for further development in this disease. In addition, thanks to the broad expression of CD19, SAR3419 may provide treatment options for B-cell leukemias that are often CD20-negative.
authors: Oncology Business Division, Sanofi, Vitry sur Seine, France. Veronique.Blanc2@sanofi-aventis.com
authors: Veronique
authors: V
authors: Blanc
authors: Anne
authors: A
authors: Bousseau
authors: Anne
authors: A
authors: Caron
authors: Chantal
authors: C
authors: Carrez
authors: Robert J
authors: RJ
authors: Lutz
authors: John M
authors: JM
authors: Lambert
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry / Q000494:pharmacology*; D018941:Antigens, CD19 / Q000276:immunology* / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D015448:Leukemia, B-Cell / Q000188:drug therapy; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000378:metabolism; D008453:Maytansine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018941:Antigens, CD19; D000972:Antineoplastic Agents, Phytogenic; D018796:Immunoconjugates; D008453:Maytansine; C569646:coltuximab ravtansine