Phase 2 trial of pTVG-HP ± pTVG-AR DNA vaccines and pembrolizumab in patients with metastatic, castration-resistant prostate cancer (mCRPC)

Clinical Snapshot

Key Findings

• P Value: p=0.80 for PFS comparison, p=0.16 for OS comparison

• Effect Size: No significant difference between treatment arms

• Primary Outcome: 6-month PFS: 51% (Arm A) vs 45% (Arm B)

• Nnt Or Sensitivity: PSA decline >50% achieved in 20% of patients in both arms

• Confidence Interval: Not reported

Clinical Application

Limited by requirement for specialised vaccine preparation and administration protocols Pembrolizumab available on PBS for other cancer types; DNA vaccines would require TGA approval and likely be restricted to clinical trials initially Patients with mCRPC who have exhausted standard therapies and are candidates for immunotherapy

Abstract

BACKGROUND: We previously reported a trial using pembrolizumab with a DNA vaccine encoding prostatic acid phosphatase (pTVG-HP) in patients with metastatic castration-resistant prostate cancer (mCRPC). Favorable clinical outcomes were associated with T-cell activation, suggesting immune response to vaccination was critical. In the current trial, we evaluated whether immunization with two vaccines, to broaden the T-cell response to other cancer-associated antigens, would elicit greater anti-tumor efficacy. MATERIALS AND METHODS: 60 patients with mCRPC were treated with vaccine on days 1 and 8 of a 3 week cycle, with pembrolizumab given on day 1 of each cycle. Patients in Arm A (n=30) received pTVG-HP as the vaccine, and patients in Arm B (n=30) received pTVG-AR (encoding the ligand-binding domain of the androgen receptor) alternating with pTVG-HP every two cycles. After eight cycles (6 months), patients continued to receive pembrolizumab alone, with the option to receive further booster immunizations at prostate-specific antigen (PSA) progression. The primary objective was 6-month progression-free survival (PFS). Secondary objectives included safety, objective response rate, PSA response rate, overall survival (OS), and immunological evaluations. RESULTS: Overall median time to progression was 24 weeks (24 weeks Arm A, 24 weeks Arm B, p=0.80). The month 6 PFS rate was 51% in Arm A and 45% in Arm B. Median OS was 2.8 years (2.5 years Arm A, 3.7 years Arm B, p=0.16). 20% of patients in each arm experienced a PSA decline of >50%. 20 patients (n=8 Arm A, n=12 Arm B) had measurable disease, and 6/20 (30%) experienced a partial response. Eight patients received booster immunizations after 6 months, 3 of whom subsequently experienced a PSA decline. Three patients in Arm B experienced creatine kinase elevation with or without increased transaminases, which were not observed in Arm A. T cell immune responses to both antigens were detected in patients treated in Arm B. CONCLUSIONS: Treatment with DNA vaccines and pembrolizumab demonstrated anti-tumor activity in terms of PSA declines and objective responses. The addition of pTVG-AR did not significantly increase measures of clinical efficacy; however, it was associated with a slight increase in toxicity to tissues that also express AR. TRIAL REGISTRATION NUMBER: NCT04090528.

References

1. 1.Kyriakopoulos, C. E., Pachynski, R. K., Eickhoff, J. C., Tonelli, T. P., Jeon, D., & McNeel, D. G. (2026). Phase 2 trial of pTVG-HP ± pTVG-AR DNA vaccines and pembrolizumab in patients with metastatic, castration-resistant prostate cancer (mCRPC). Journal for Immunotherapy of Cancer, Article jitc-2025-014323. https://doi.org/10.1136/jitc-2025-014323