PVX-410 is a multi-peptide therapeutic cancer vaccine being developed for patients with smoldering multiple myeloma. The goal of treatment with PVX-410 is to induce an immune response against multiple myeloma (MM) cells by "educating" the patient's cytotoxic T lymphocytes (CTLs) to target specific tumor associated antigens. By targeting multiple antigens simultaneously, multiple peptides are employed to target the tumor cell heterogeneity observed in MM, as in all cancers, and decrease the likelihood of tumor cells developing resistance to CTLs. The vaccine is composed of a unique combination of four peptides which specifically target the highly over-expressed tumor antigens XBP1, CD138 and CS1.
PVX-410 has the potential to be utilized as a stand-alone therapy and in combination with other immunotherapeutic drug-like checkpoint inhibitors. In 2013, PVX-410 was granted orphan drug designation from the U.S. Food and Drug Administration for the treatment of multiple myeloma.
August 16, 2018
Overall, 14 (64%) patients were men and the median age at enrollment was 56 years in the monotherapy and 57 years in the combination cohorts (overall range, 39-82 years). Six of 12 patients in the monotherapy and 9 of 10 in the combination cohorts were at moderate risk. The PVX-410 vaccine was well tolerated. The most common AEs were mild-to-moderate injection site reactions and constitutional symptoms. Of note, PVX-410 was immunogenic as monotherapy (10 of 11 patients) and in combination with lenalidomide (9 of 9 patients), as demonstrated by an increase in percentage of tetramer-positive cells and IFN-γ cells in the CD3+CD8+ cell population. The combination resulted in greater mean fold increases in proportions of CD3+CD8+ T cells that were tetramer-positive and IFN–γ-positive, statistically significant for IFN–γ-positive cells after 2 and 4 vaccinations. An increase and persistence of vaccine-specific effector memory cells was noted. In total, 7 of 12 patients in the PVX-410–alone cohort had stable disease with 2 of 3 (low-dose cohort) and 1 of 9 of the target-dose cohort progressing (median TTP, 36 weeks), whereas 5 of 12 patients in the combination cohort showed, clinical response, with 1 patient progressing (median TTP not reached).