VLS-211 / Merck (MSD) - LARVOL DELTA

Preclinical evaluation of the ROR1-targeting antibody-drug conjugates zilovertamab vedotin and VLS-211 against B-cell ALL patient-derived xenografts. (PubMed, Hemasphere) - "Notably, we identified pediatric patients with TCF3::HLF gene fusions, which is a highly chemoresistant ALL subtype, as having some of the highest ROR1 expression in pediatric ALL and show that this subtype is susceptible to targeting ROR1 via ADC-based therapy. Given that ZV has a favorable toxicity profile in patients with hematological malignancies, it may have some utility in the treatment of very high-risk pediatric B-ALL, particularly cases with TCF3::HLF gene fusions."

Journal • Preclinical • Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Pediatrics • PBX1 • ROR1 • TCF3

The ROR1 antibody-drug conjugate, MK-2140, enhances the efficacy of established drugs in preclinical models of pediatric acute lymphoblastic leukemia (AACR 2024) - "Vincristine (0.15 mg/kg once weekly), dexamethasone (5 mg/kg daily x 5) and Lasparaginase (1,250 U/kg daily x 5) (VXL) were administered intraperitoneally for 3 weeks, followed by MK-2140 (5 mg/kg weekly x 3 weeks). MK-2140 and VLS-211 exerted significant single-agent in vivo activity against a panel of pediatric ALL PDXs. MK-2140 significantly enhanced the efficacy of an induction-type regimen and should be considered for further evaluation in a minimal residual disease setting."

ADC • Preclinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • PTPRC • ROR1

[VIRTUAL] Evaluation of ROR1-targeted antibody-drug conjugates against ROR1-expressing pediatric preclinical models - a report from the pediatric preclinical testing consortium (PPTC) (AACR 2021) - "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 and VLS-211 showed expression-level dependent activity against ALL and EWS models. These results support ROR1 as a relevant immuno-oncology target for the subset of B-ALL and Ewing sarcoma cases with elevated ROR1 expression. Further research is required to identify the optimal payload for ROR1 ADCs for use against pediatric cancers."

IO biomarker • Preclinical • Acute Lymphocytic Leukemia • Ewing Sarcoma • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Oncology • Sarcoma • Solid Tumor • ABL1 • BCR • ETV6 • PBX1 • ROR1 • RUNX1 • TCF3