title: An Open-Label, Dose-Escalation Phase I Study of Anti-TYRP1 Monoclonal Antibody IMC-20D7S for Patients with Relapsed or Refractory Melanoma.
abstract: OBJECTIVE
  Tyrosinase-related protein-1 (TYRP1) is a transmembrane glycoprotein that is specifically expressed in melanocytes and melanoma cells. Preclinical data suggest that mAbs targeting TYRP1 confer antimelanoma activity. IMC-20D7S is a recombinant human IgG1 mAb targeting TYRP1. Here, we report the first-in-human phase I/Ib trial of IMC-20D7S.
  
  
  METHODS
  The primary objective of this study was to establish the safety profile and the MTD of IMC-20D7S. Patients with advanced melanoma who progressed after or during at least one line of treatment or for whom standard therapy was not indicated enrolled in this standard 3 + 3 dose-escalation, open-label study. IMC-20D7S was administered intravenously every 2 or 3 weeks.
  
  
  RESULTS
  Twenty-seven patients were enrolled. The most common adverse events were fatigue and constipation experienced by nine (33%) and eight (30%) patients, respectively. There were no serious adverse events related to treatment, no discontinuations of treatment due to adverse events, and no treatment-related deaths. Given the absence of dose-limiting toxicities, an MTD was not defined, but a provisional MTD was established at the 20 mg/kg every 2-week dose based on serum concentration and safety data. One patient experienced a complete response. A disease control rate, defined as stable disease or better, of 41% was observed.
  
  
  CONCLUSIONS
  IMC-20D7S is well tolerated among patients with advanced melanoma with evidence of antitumor activity. Further investigation of this agent as monotherapy in selected patients or as part of combination regimens is warranted. Clin Cancer Res; 22(21); 5204-10. ©2016 AACR.
authors: Memorial Sloan Kettering Cancer Center, Ludwig Center for Cancer Immunotherapy, New York, New York.
authors: Danny N
authors: DN
authors: Khalil
authors: Memorial Sloan Kettering Cancer Center, Ludwig Center for Cancer Immunotherapy, New York, New York.
authors: Michael A
authors: MA
authors: Postow
authors: Merck Research Laboratories, North Wales, Pennsylvania.
authors: Nageatte
authors: N
authors: Ibrahim
authors: Eli Lilly and Company, New York, New York.
authors: Dale L
authors: DL
authors: Ludwig
authors: Sotio, Prague, Czech Republic.
authors: Jan
authors: J
authors: Cosaert
authors: Eli Lilly and Company, New York, New York.
authors: Siva Rama Prasad
authors: SR
authors: Kambhampati
authors: Eli Lilly and Company, New York, New York.
authors: Shande
authors: S
authors: Tang
authors: Kyowa Hakko Kirin Pharma, Inc., Princeton, New Jersey.
authors: Dmitri
authors: D
authors: Grebennik
authors: Eli Lilly and Company, New York, New York.
authors: John Sae Wook
authors: JS
authors: Kauh
authors: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors: Heinz-Josef
authors: HJ
authors: Lenz
authors: Massachusetts General Hospital, Boston, Massachusetts.
authors: Keith T
authors: KT
authors: Flaherty
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors: F Stephen
authors: FS
authors: Hodi
authors: Massachusetts General Hospital, Boston, Massachusetts.
authors: Donald P
authors: DP
authors: Lawrence
authors: Memorial Sloan Kettering Cancer Center, Ludwig Center for Cancer Immunotherapy, New York, New York. wolchokj@mskcc.org.
authors: Jedd D
authors: JD
authors: Wolchok
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology*; D008875:Middle Aged; D010088:Oxidoreductases / Q000276:immunology*; D011994:Recombinant Proteins / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D010088:Oxidoreductases; C489799:TYRP1 protein, human