> Details

Janku, Filip; Han, Sae-Won; Doi, Toshihiko; Amatu, Alessio; Ajani, Jaffer A.; Kuboki, Yasutoshi; Cortez, Alex; Cellitti, Susan E.; Mahling, Ping C.; Subramanian, Kulandayan; Schoenfeld, Heidi A.; Choi, Sarah M.; Iaconis, Lori A.; Lee, Lang Ho; Pelletier, Marc R.; Dranoff, Glenn; Askoxylakis, Vasileios; Siena, Salvatore

Preclinical Characterization and Phase I Study of an Anti–HER2-TLR7 Immune-Stimulator Antibody Conjugate in Patients with HER2+ Malignancies

Reference
management

Bookmarks

Remove from
bookmarks

Share this on Whatsapp

Close

Bookmarks



You can manage bookmarks using lists, please log in to your user account for this.
  • Media type: E-Article
  • Title: Preclinical Characterization and Phase I Study of an Anti–HER2-TLR7 Immune-Stimulator Antibody Conjugate in Patients with HER2+ Malignancies
  • Contributor: Janku, Filip; Han, Sae-Won; Doi, Toshihiko; Amatu, Alessio; Ajani, Jaffer A.; Kuboki, Yasutoshi; Cortez, Alex; Cellitti, Susan E.; Mahling, Ping C.; Subramanian, Kulandayan; Schoenfeld, Heidi A.; Choi, Sarah M.; Iaconis, Lori A.; Lee, Lang Ho; Pelletier, Marc R.; Dranoff, Glenn; Askoxylakis, Vasileios; Siena, Salvatore
  • Published: American Association for Cancer Research (AACR), 2022
  • Published in: Cancer Immunology Research, 10 (2022) 12, Seite 1441-1461
  • Language: English
  • DOI: 10.1158/2326-6066.cir-21-0722
  • ISSN: 2326-6066; 2326-6074
  • Origination:
  • Footnote:
  • Description: Abstract Immune-stimulator antibody conjugates (ISAC) combining tumor-targeting monoclonal antibodies with immunostimulatory agents allow targeted delivery of immune activators into tumors. NJH395 is a novel, first-in-class ISAC comprising a Toll-like receptor 7 (TLR7) agonist conjugated to an anti-HER2 antibody via a noncleavable linker payload. Preclinical characterization showed ISAC-mediated activation of myeloid cells in the presence of antigen-expressing cancer cells, with antigen targeting and TLR7 agonism contributing to antitumor activity. Safety, efficacy, immunogenicity, pharmacokinetics, and pharmacodynamics were investigated in a phase I, multicenter, open-label study in patients with HER2+ non-breast advanced malignancies (NCT03696771). Data from 18 patients enrolled in single ascending dose escalation demonstrated delivery of the TLR7-agonist payload in HER2+ tumor cells and induction of type I IFN responses, which correlated with immune modulation in the tumor microenvironment. Cytokine release syndrome was a common, but manageable, drug-related adverse event. Antidrug antibodies and neuroinflammation at high doses represented significant clinical challenges. Data provide proof-of-mechanism and critical insights for novel immunotherapies.
  • Access State: Open Access