DEVELOPMENT IN SMM
The Phase 1/2a dose escalation study of PVX-410 enrolled a total of 22 patients with smoldering myeloma at moderate or high risk of progression to multiple myeloma. Twelve patients were enrolled in the dose escalation stage of the study and received PVX-410 plus adjuvant and 10 patients received PVX-410 plus adjuvant and lenalidomide.
Lenalidomide (Revlimid®, Celgene, Corp.) is an analogue of thalidomide with immunomodulatory, antiangiogenic, and antineoplastic properties1. Given the clinical experience in high risk SMM and the known immunomodulatory properties, OncoPep investigated whether the co-administration of lenalidomide could enhance the T cell-mediated immune response induced by PVX-410.
All tested doses of PVX-410 were found to be well tolerated, both as monotherapy and in combination with lenalidomide. An immune response to PVX-410 was observed with PVX-410 alone, which was enhanced by the addition of lenalidomide. Final results from the study were presented in a poster presentation [LINK TO POSTER PRESENTATION] at the American Society of Hematology in December 2016. Based on these promising findings, OncoPep’s is planning to initiate a Phase 2 clinical trial of PVX-410 to determine the optimal dosing regimen in the moderate and high risk smoldering multiple myeloma patient population.
1 Celgene Corporation. (2017). Revlimid®: Highlights of prescribing information. Retrieved from http://media.celgene.com/content/uploads/revlimid-pi.pdf
Additional clinical trials are being developed to evaluate the combination of PVX-410 plus checkpoint antibodies to the PD-1/PD-L1 ligand. Blocking immune checkpoint receptors on activated T cells should enhance the vaccine-stimulated immune response. The premise of the checkpoint antibody strategy is to combine a vaccine, such as PVX-410, that will stimulate a cellular response to critical antigens on MM cells while simultaneously removing the PD-1/PD-L1 mediated inhibition of the patient’s immune response. PVX-410 is currently being evaluated in an investigator initiated study in combination with an immunomodulator plus the PD1/PDL1 checkpoint inhibitor, durvalumab (Celgene, Inc.). A second investigator study is planned to evaluate PVX-410 in combination with the PD-1/PD-L1 checkpoint inhibitor, nivolumab (Bristol Myers Squibb).