Vitalize Trial: A Phase 2b, Open-Label, Multicenter, Randomized Parallel-Group, Two-Stage, Study of the Novel Immunotherapeutic, Maveropepimut-S, and Pembrolizumab with and without Intermittent Low-Dose Cyclophosphamide, in Subjects with Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Background

Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin 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 their safety profiles. 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.

Methods

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 patients at 65 global study sites. As of now, 21 sites are actively recruiting in US, Canada, Australia, New-Zealand, and France. Enrollment has begun.

Matasar:ImmunoVaccine Technologies: Honoraria, Research Funding; GlaxoSmithKline: Honoraria, Research Funding; Teva: Consultancy; AstraZeneca: Consultancy; ADC Therapeutics: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Janssen: Honoraria, Research Funding; Karyopharm: Consultancy; IMV Therapeutics: Consultancy, Honoraria; Pharmacyclics: Honoraria, Research Funding; Rocket Medical: Consultancy, Research Funding; Merck: Consultancy, Current equity holder in private company; TG Therapeutics: Consultancy; Epizyme: Consultancy, Honoraria; Juno Therapeutics: Consultancy; IGM Biosciences: Research Funding; Genentech, Inc.: Consultancy, Honoraria, Research Funding; F. Hoffmann-La Roche Ltd.: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy; Bayer: Consultancy, Honoraria, Research Funding. Solh:Partner Therapeutics: Research Funding; ADC Therapeutics: Research Funding. Teti:IMV inc.: Current Employment; The Janssen Pharmaceutical Companies of Johnson & Johnson: Ended employment in the past 24 months. Mody:CytoDyn, Inc: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; IMV inc.: Current Employment, Current holder of stock options in a privately-held company. Fiset:IMV inc.: Current Employment. Graff:IMV inc.: Current Employment, Current equity holder in private company, Current holder of stock options in a privately-held company, Other: Travel & accommodations, Patents & Royalties, Research Funding; Avicenna Bio: Consultancy, Other: Travel & accommodations; OncXerna: Consultancy, Other: Travel & accommodations; HiberCell: Ended employment in the past 24 months, Other: Travel & accommodations, Patents & Royalties.