646TiP VITALIZE: A phase IIb, open-label, multicenter, randomized parallel-group, two-stage, study of maveropepimut-S, pembrolizumab, with or without intermittent low-dose cyclophosphamide, in r/r DLBCL

Abstract

Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin’s lymphoma in adults, and up to 40% of patients are refractory to front-line therapy or experience a relapse. In the relapsed/refractory (r/r) setting, novel treatment options are available, but many patients relapse following or are ineligible for such treatment options, due in part to the safety profile. Thus, more effective, better tolerated therapeutic options are needed. Maveropepimut-S (MVP-S) leverages the DPX platform, a non-aqueous, lipid-based delivery system, to educate a specific, and persistent T cell-based immune response to HLA-restricted peptides of survivin, a cancer-associated protein commonly upregulated in advanced DLBCL. In a prior study in patients with r/r DLBCL (SPiReL), MVP-S with pembrolizumab and low dose, intermittent cyclophosphamide (CPA) led to durable complete and partial responses, and persistent, survivin-specific T cells, particularly in patients with PD-L1+ disease. Importantly, treatment was well-tolerated. Further exploration of the regimen in r/r DLBCL is warranted to confirm and extend these encouraging results. The VITALIZE trial (NCT04920617) is a phase 2b, open-label, randomized trial of MVP-S and pembrolizumab, with or without intermittent low-dose CPA. Eligible patients have r/r persistent or progressive DLBCL following ≥ 2 lines of prior systemic therapy and are ineligible for, or have relapsed after, ASCT and/or CAR-T. Using a Simon’s Two-Stage Design, patients are randomized (1:1) to: Arm 1: MVP-S, pembrolizumab and CPA or Arm 2: MVP-S and pembrolizumab, and will be treated for up to 2 years. The primary objective of the study is centrally assessed ORR, and secondary endpoints include PFS, DoR, DCR, OS and safety. Exploratory objectives include characterization of outcomes based on PD-L1 expression, and survivin-specific immunogenicity in baseline and on-treatment blood and tissue samples. This study will enroll up to 102 eligible subjects at 65 global study sites. Enrollment has begun. NCT04920617. IMV inc.