3142 - Multicenter Phase I Trial of a DNA Vaccine Encoding the Androgen Receptor Ligand Binding Domain (pTVG-AR, MVI-118) in Patients with Metastatic Prostate Cancer

Background

Preclinical studies have demonstrated that a DNA vaccine encoding the androgen receptor ligand-binding domain (AR LBD) can elicit CD8+ T cells specific for the AR LBD, delay disease progression and prolong survival of prostate tumor-bearing animals. Vaccination of tumor-bearing mice treated with androgen deprivation (AD) led to a delay in the emergence of castration-resistant disease. This same DNA vaccine (pTVG-AR, MVI-118) was evaluated in a phase I clinical trial in men with metastatic prostate cancer (mPC) on AD therapy.

Methods

40 patients with mPC, within 6 months of beginning standard AD therapy, were randomly assigned to receive pTVG-AR on one of two different treatment schedules, and with or without GM-CSF used as an adjuvant. Ten total vaccinations were given over 1 year, and patients were followed for 18 months. The primary objectives were safety and immune activity. Secondary objectives were to evaluate different schedules, the requirement for GM-CSF, and whether treatment was associated with PSA progression-free survival (PSA PFS).

Results

Between 2015 and 2017, 40 patients were enrolled at 3 centers. 27 patients completed treatment and 18 months of follow-up. Eleven patients (28%) had a PSA progression event. No grade 3 or 4 adverse events were observed. Samples from 30 patients were available for immune analysis. 14/30 (47%) developed Th1 biased immunity to the AR LBD as determined by IFNγ or granzyme B ELISPOT that was detectable at least twice after beginning treatment. Differences in immune responses were observed with different schedules, but not with GM-CSF adjuvant. Patients who developed immunity had a significantly prolonged PSA PFS compared to patients without immunity (HR = 0.18, 95% CI: 0.04-0.92, p = 0.040).

Conclusions

This trial showed that pTVG-AR was safe and immunologically active in patients with mPC, and identified a preferred schedule of administration. Association between immunity and PSA PFS suggests treatment may delay the time to castration resistance, similar to observations in preclinical studies. Future studies will evaluate pTVG-AR in earlier stages of disease, and in combination with other agents.

Clinical trial identification

NCT02411786.

Editorial acknowledgement

Legal entity responsible for the study

Douglas McNeel.

Funding

Madison Vaccines, Inc.

Disclosure

D.G. McNeel: Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Licensing / Royalties, Officer / Board of Directors: Madison Vaccines Inc; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Merck. R. Lesniewski: Leadership role, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: Madison Vaccines Inc. B. Olson: Licensing / Royalties: Madison Vaccines Inc. C. Kyriakopoulos: Research grant / Funding (institution): Madison Vaccines Inc. All other authors have declared no conflicts of interest.