Long Term Update on Phase I/II Trial with Immucin Anti-MUC1 Signal Peptide Vaccine for Multiple Myeloma Patients with Residual Disease or Progression
Authors: Carmon Lior , Avivi Irit , Kovjazin Riva , Dary Lillian , Shapira Michael Y 
Published: October 2019

Abstract
Background:
ImMucin is a 21-mer long peptide therapeutic vaccine encoding the entire signal peptide (SP) domain of the MUC1 tumor-associated antigen, which is over expressed by most hematological tumors including multiple myeloma (MM).
Results from first in man phase I/II study (VAXIL-001) demonstrated that 100 micrograms (ug) ImMucin combined with 250ug hGM-CSF is highly tolerable and can induce a robust, diversified MUC1 SP-specific T cell and B cell immunity in most patients, across major histocompatibility complex barrier. ImMucin vaccination also led to a significant decline in soluble MUC1 (sMUC1) in 9/10 patients with abnormal prevaccination levels, accompanied with disease stabilization.
Methods:
This current follow–up phase I/II study investigated the long term safety, quality of Life (QOL) (primary endpoint) and efficacy (both immunity and clinical response a secondary endpoint), of ImMucin, obtained in VAXIL-001 study, in participant MM subjects that didn’t required further treatment post vaccination. Patients were being evaluated once every 3 months in the first year and twice a year at the following years till progression or Q4-2015. QOL easement was assessed every visit using the SF-36 questionnaire. Immunomonitoring analysis included; CD62L+effecter memory marker, ImMucin-specific IFN-g production in CD4+ and CD8+ T-cells and anti-MUC1 SP antibody production. Clinical response was assessed according to the international myeloma working group response criteria sMUC1 levels were also evaluated every visit.
Results:
Long- term safety was encouraging, with no evidence for any adverse events. Additionally, the average QOL score was maintained throughout the study. Immunity, determined by INF-g production by both CD4+ and CD8+ T-cells and anti-MUC1 SP antibodies, was maintained for 6-10 and 10-12 months post vaccination respectively. The predominant T-cell phenotype during the post vaccination period was characterized with CD62L+ CD4 and CD8+ T-cells. At 13-41.3 months after the completion of the VAXIL-001 study (measured for first and last patients, respectively), 12/15 patients are alive. Median time from first vaccination was 24 months (range 2.5-41.3), at which time 10/15 patients had a PD. Disease progressed during the vaccination period (up to week 26) in 4/15 patients and during the follow up period in 6/15 patients. Notably, 5/15 patients maintained their CR (n=3) or SD (n=2).
Notably, clinical response was associated with low-intermediate PDL-1 bone marrow (BM) levels prior and post vaccination, while high PDL-1 BM levels were associated with temporary response and progression. Moreover, sMUC1 levels have moderately increased during the follow up period (x>600pg/ml), though didn’t reach initial prevaccination values.
Conclusions
ImMucin demonstrated an encouraging short and long-term safety profile. Vaccination induced a remarkable anti-MM immune response. However, immunity was transient suggesting a need for boosting. Interestingly, durable disease stabilization was achieved in third of the patients, continuing despite loss of immune response in peripheral blood. Moreover, the encouraging responses to subsequent therapies employed at clinical progression, suggest this novel approach to be potentially valuable in the setting of maintenance and/or early biochemical progression.

Disclosures
Carmon: Vaxil BioTherapeutics Ltd. : Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Kovjazin:Vaxil BioTherapeutics Ltd. : Employment. Shapira:Vaxil BioTherapeutics Ltd. : Consultancy.