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PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec) is a cancer immunotherapy candidate in clinical development by Bavarian Nordic for the treatment of all prostate cancer although clinical trials are focusing on more advanced cases of metastatic castration-resistant prostate cancer (mCRPC). PROSTVAC is a vaccine designed to enable the immune system to recognize and attack prostate cancer cells by triggering a specific and targeted T cell immune response to cancer cells that express the tumor-associated antigen prostate-specific antigen (PSA).

PROSTVAC utilizes recombinant poxviruses that express PSA, along with 3 immune-enhancing costimulatory molecules collectively designated as TRICOM (LFA-3, ICAM-1, and B7.1) to stimulate an immune response. Treatment is initiated by subcutaneous administration of a priming dose of vaccinia encoding PSA-TRICOM, followed by 6 subsequent boosting doses of fowlpox encoding the same PSA-TRICOM cassette. Using this heterologous prime-boost dosing regimen, the immune system becomes focused on inducing PSA-specific T cell responses, designed to kill tumor cells expressing PSA.

Clinical development

PROSTVAC is being developed in partnership with the National Cancer Institute under a formal Cooperative Research and Development Agreement and has been the subject of multiple ongoing and completed clinical studies, including the global Phase 3 PROSPECT study underway in patients with asymptomatic or minimally symptomatic metastatic prostate cancer (mCRPC). This Phase 3 study is designed to validate positive clinical data from a randomized, controlled, double-blind Phase 2 clinical trial that enrolled 125 minimally symptomatic mCRPC patients. The Phase 2 study's secondary endpoint demonstrated that patients who received PROSTVAC had a median overall survival that was 9.9 months longer than the control group (26.2 versus 16.3 months)(p. < .01) and a reduction in the risk of death. PROSTVAC was generally well tolerated, with the most common side effects including injection site reactions, fever, fatigue, and nausea.

Based on non-clinical data supporting the scientific rationale for combination therapy with PROSTVAC, additional clinical trials are underway to evaluate the potential clinical benefit of combining PROSTVAC with different treatment modalities such as hormonal therapies (e.g. androgen inhibitors), radiopharmaceuticals and immune checkpoint inhibitors in the treatment of prostate cancer.

Commercialization

In 2015, Bristol-Myers Squibb obtained from Bavarian Nordic an "exclusive option to license and commercialize Prostvac". Under a separate agreement, Bavarian Nordic would "undertake the future commercial manufacturing of Prostvac".

References

1. "Survival Benefit Propels Prostate Cancer Vaccine to Phase III Trial". OncLive. June 2013. 2 (3). 3 July 2013. Retrieved 2014-10-31.
2. "A Randomized, Double-blind, Phase 3 Efficacy Trial of PROSTVAC-V/F +/- GM-CSF in Men With Asymptomatic or Minimally Symptomatic Metastatic Castrate-Resistant Prostate Cancer (Prospect)". Clinicaltrials.gov. Retrieved 31 October 2014.
3. Revised Overall Survival Analysis of a Phase II, Randomized, Double-Blind, Controlled Study of PROSTVAC in Men With Metastatic Castration-Resistant Prostate Cancer Philip W. Kantoff, James L. Gulley, and Cesar Pico-Navarro Journal of Clinical Oncology 2017 35:1, 124-125
4. Kantoff PW, Schuetz TJ, Blumenstein BA, Glode LM, Bilhartz DL, Wyand M, Manson K, Panicali DL, Laus R, Schlom J, Dahut WL, Arlen PM, Gulley JL, Godfrey WR (2010). "Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer". J Clin Oncol. 28 (7): 1099–105. doi:10.1200/JCO.2009.25.0597. PMC 2834462. PMID 20100959.
5. Madan RA, Mohebtash M, Arlen PM, Vergati M, Rauckhorst M, Steinberg SM, Tsang KY, Poole DJ, Parnes HL, Wright JJ, Dahut WL, Schlom J, Gulley JL (2012). "Ipilimumab and a poxviral vaccine targeting prostate-specific antigen in metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial". The Lancet Oncology. 13 (5): 501–8. doi:10.1016/S1470-2045(12)70006-2. PMC 6359905. PMID 22326924.
6. Jochems C, Tucker JA, Tsang KY, Madan RA, Dahut WL, Liewehr DJ, Steinberg SM, Gulley JL, Schlom J (2014). "A combination trial of vaccine plus ipilimumab in metastatic castration-resistant prostate cancer patients: immune correlates". Cancer Immunol Immunother. 63 (4): 407–18. doi:10.1007/s00262-014-1524-0. PMC 6314199. PMID 24514956.
7. ^ Staff (1 April 2015). "Bavarian Nordic Could Reap $975M in Prostate Cancer Deal with BMS". Genetic Engineering & Biotechnology News (Paper). 35 (7): 12. Retrieved 2016-06-12.

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