Evaluation of ROR1-targeted antibody-drug conjugates against ROR1-expressing pediatric preclinical models - a report from the pediatric preclinical testing consortium (PPTC)

Abstract

Abstract 3038

Introduction: ROR1 is an orphan-receptor tyrosine kinase-like surface antigen that is expressed primarily during development but is not expressed on normal adult tissues. ROR1 is expressed on multiple adult hematologic and solid cancers, making it a target for antibody-based therapies. UC-961 (cirmtuzumab), a humanized IgG1 monoclonal antibody, binds with high affinity to a specific extracellular epitope of human ROR1 and rapidly internalizes and traffics to lysosomes. VLS-101 is an ADC developed by conjugating UC-961 to a cleavable linker with an MMAE payload. VLS-211 was generated by conjugating UC-961 with a PNU payload. VLS-101 is in clinical development for adults with hematologic and solid cancers and has received FDA Fast Track and Orphan Drug designation for the treatment of patients with mantle cell lymphoma. To better define the utility of ROR1 as an immuno-oncology target for pediatric cancers, we evaluated VLS-101 and VLS-211 against pediatric preclinical models selected based on ROR1 expression.

Proceedings: AACR Annual Meeting 2021; April 10-15, 2021 and May 17-21, 2021; Philadelphia, PA