lusvertikimab (OSE-127)

P2, N=48, Completed, Institut de Recherches Internationales Servier | Phase classification: P2a --> P2

Lusvertikimab-mediated in vitro ADCP levels significantly correlated with CD127 expression levels and the reduction of leukemia burden upon treatment of PDX animals in vivo. Altogether, through its dual mode of action and good safety profile, Lusvertikimab may represent a novel immunotherapy option for any CD127-positive ALL, particularly in combination with standard-of-care polychemotherapy.

In fact, ADCP levels induced by OSE-127 treatment in vitro correlated with its capacity to reduce ALL blasts in the blood of PDX mice in vivo. Altogether, through its dual mode of action, OSE-127 may represent a powerful novel immunotherapy option for ALL patients, including cases with dysregulated IL7R signaling, particularly in combination with standard of care polychemotherapy.

We previously reported high preclinical efficacy of OSE‑127 in BCP-ALL patient derived xenograft (PDX) models of different cytogenetic backgrounds (Lenk and Baccelli et al...Finally, we conducted a phase2-like PDX overt leukemia study testing OSE‑127 alone or in combination with Dexamethasone/Vincristine/PEG-Asparaginase chemotherapy employing PDX samples with high CD127 expression (6 BCP-ALL and 3 T-ALL-PDX samples with >50% CD127+ cells in flow cytometry analysis)...and D.M.S. share senior authorship

Antibody-based immunotherapies like Blinatumomab have improved BCP-ALL outcome, yet these can quickly turn ineffective due to CD19 antigen escape. Of note, OSE-127 therapy response associated with IL7R expression levels on BCP-ALL cells and no significant downregulation of the IL7R antigen was observed upon OSE-127 treatment. Taken together, our data demonstrate that IL7R-targeting using OSE-127, which has already demonstrated a good safety profile in healthy volunteers, is an efficient approach for BCP-ALL immunotherapy and may be particularly beneficial for patients with high IL7R-expression and/or relapsed/refractory disease after CD19-directed therapy.