Abstract LB048: An adjuvant personalized neoantigen peptide vaccine for the treatment of malignancies (PGV-001)
Authors: Marron Thomas Urban , Saxena Mansi , Bhardwaj Nina , Meseck Marcia , Rubinsteyn Alex , Finnigan John , Kodysh Julia , Blazquez Ana , O'Donnel Tim , Galsky Mathew , Doroshow Deborah , Miles Brett , Misiukiewicz Krysztof , Irie Hanna , Tiersten Amy , Parekh Samir , Posner Marshall , Wolf Andrea , Mandeli John , Brody Rachel , Gnjatic Sacha , Schadt Eric , Friedlander Philip , Hammerbacher Jeffrey 
Published: July 2021

Abstract
Background: The majority of novel cancer immunotherapies rely on adequate priming of T cells to tumor-specific neoantigens, which is believed to be lacking in patients who do not respond to therapy. We developed a personalized genomic vaccine (PGV-001) in which patient-specific synthetic neoantigen peptides (25 mer),are formulated and administered to patients with multiple cancer types in the adjuvant setting (NCT02721043). Methods: This trial enrolled patients whom had undergone curative-intent surgery (solid tumor patients) or autologous stem cell transplant (multiple myeloma patients), and for whom there was &gt;30% chance of recurrence. Sequencing of tumor and germline DNA and RNA was performed and the OpenVax custom computation pipeline was used to identify candidate neoantigens; this platform ranks transcribed mutations using predicted MHC-I binding affinity and neoantigen abundance. A maximum of 10 peptides were synthesized per patient. Peptides were administered over the course of 27 weeks with poly-ICLC and a tetanus helper peptide. Primary objectives were to determine the safety and tolerability of vaccination, feasibility of vaccine production and administration, and immunogenicity. Results: Within 15 patients enrolled, the OpenVax pipeline identified an average of 67.1 neoantigens/patient (range 8-193), only two patients did not have adequate number of neoantigens identified to synthesize 10 peptides. 13 of the 15 patients received PGV-001, including 10 patients with solid tumor diagnoses and 3 patients with multiple myeloma, 11 of whom received all 10 doses, while 1 experienced progression of disease while on treatment. The vaccine was well tolerated, with grade 1 injection site reactions in 31% of patients, and grade 1 fever in one patient; there were no other significant adverse events. While one patient was lost to follow-up, of the remaining 12 patients the median progression-free survival from the time of their surgery or transplant of 618 days. With a mean follow-up of 925 days, 4 patients remain without evidence of disease, 4 patients are receiving subsequent lines of therapy, and 4 patients have died, though notably only two with documented recurrence of their malignancy. Initial analysis of the patient samples analyzed confirms immunogenicity. T cell responses were measured using ex vivo ELISpot and intracellular cytokine staining following expansion with neoantigen peptide libraries, both demonstrating induction of IFN-gamma, TNF-alpha and IL-2. Notably, robust T cell reactivity was only seen at the completion of all 10 vaccines, supporting the need for a prolonged schedule. Conclusions: PGV-001 was successfully synthesized for 15 patients and administered successfully to 13 patients without significant adverse events. Immune monitoring of immunogenicity is ongoing, with initial analysis demonstrating induction of neoantigen-specific CD4 and CD8 T cell expansion.
Citation Format: Thomas Urban Marron, Mansi Saxena, Nina Bhardwaj, Marcia Meseck, Alex Rubinsteyn, John Finnigan, Julia Kodysh, Ana Blazquez, Tim O'Donnel, Mathew Galsky, Deborah Doroshow, Brett Miles, Krysztof Misiukiewicz, Hanna Irie, Amy Tiersten, Samir Parekh, Marshall Posner, Andrea Wolf, John Mandeli, Rachel Brody, Sacha Gnjatic, Eric Schadt, Philip Friedlander, Jeffrey Hammerbacher. An adjuvant personalized neoantigen peptide vaccine for the treatment of malignancies (PGV-001) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB048.