Data from ABBV-085, Antibody–Drug Conjugate Targeting LRRC15, Is Effective in Osteosarcoma: A Report by the Pediatric Preclinical Testing Consortium

Abstract

<div>Abstract<p>Membrane protein leucine–rich repeat containing 15 (LRRC15) is known to be expressed in several solid tumors including osteosarcoma. ABBV-085, an antibody–drug conjugate against LRRC15, conjugated to monomethyl auristatin E (MMAE), was studied in osteosarcoma patient-derived xenografts (PDXs) by the Pediatric Preclinical Testing Consortium (PPTC). <i>LRRC15</i> expression data were obtained from PPTC RNA-sequencing data for the PDX models. The TARGET database was mined for <i>LRRC15</i> expression in human osteosarcoma. Protein expression was confirmed via IHC in three PDX models. Seven osteosarcoma PDX models (OS1, OS9, OS33, OS34, OS42, OS55, and OS60) with varying <i>LRRC15</i> gene expression were studied. ABBV-085 was administered at 3 mg/kg (OS33), 6 mg/kg (all seven PDXs), and 12 mg/kg (OS60) weekly for 4 consecutive weeks via intraperitoneal injection. Control cohorts included vehicle and an isotype MMAE-linked antibody. Tumor volumes and responses were reported using PPTC statistical analysis. OS1, OS33, OS42, OS55, and OS60 had high <i>LRRC15</i> expression while OS9 and OS34 had low <i>LRRC15</i> expression. ABBV-085 inhibited tumor growth in six of seven PDX models as compared with vehicle control and significantly improved event-free survival in five of seven models as compared with isotype controls. Two models showed maintained complete responses while all others showed progressive disease. Response correlated with LRRC15 expression. ABBV-085’s antitumor activity against osteosarcoma PDX suggests LRRC15 may be a rational target for pursuing clinical trials in patients with this disease.</p></div>