Phase 2 trial of a DNA vaccine (pTVG-HP) and nivolumab in patients with castration-sensitive non-metastatic (M0) prostate cancer
Clinical/Translational Cancer Immunotherapy
Male
Nivolumab
Positron Emission Tomography Computed Tomography
Vaccines, DNA
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Humans
Prostatic Neoplasms
Castration
Prostate-Specific Antigen
RC254-282
DOI:
10.1136/jitc-2023-008067
Publication Date:
2023-12-15T07:07:31Z
AUTHORS (8)
ABSTRACT
PurposeWe have previously reported that a plasmid DNA vaccine encoding prostatic acid phosphatase (pTVG-HP) had greater clinical activity when given in combination with pembrolizumab to patients with metastatic, castration-resistant prostate cancer. The current trial was conducted to evaluate vaccination with PD-1 blockade, using nivolumab, in patients with early, recurrent (M0) prostate cancer.MethodsPatients with M0 prostate cancer were treated with pTVG-HP (100 µg administered intradermally) and nivolumab (240 mg intravenous infusion) every 2 weeks for 3 months, and then every 4 weeks for 1 year of total treatment. Patients were then followed for an additional year off treatment. The primary objectives were safety and complete prostate-specific antigen (PSA) response (PSA<0.2 ng/mL).Results19 patients were enrolled. No patients met the primary endpoint of complete PSA response; however, 4/19 (21%) patients had a PSA decline >50%. Median PSA doubling times were 5.9 months pretreatment, 25.6 months on-treatment (p=0.001), and 9.0 months in the subsequent year off-treatment. The overall median radiographic progression-free survival was not reached. Grade 3 or 4 events included adrenal insufficiency, fatigue, lymphopenia, and increased amylase/lipase. 9/19 (47%) patients developed immune-related adverse effects (irAE). The development of irAE and increased CXCL9 were associated with increased PSA doubling time. Quantitative NaF PET/CT imaging showed the resolution of subclinical lesions along with the development of new lesions at each time point.ConclusionsIn this population, combining nivolumab with pTVG-HP vaccination was safe, and immunologically active, prolonged the time to disease progression, but did not eradicate disease. Quantitative imaging suggested that additional treatments targeting mechanisms of resistance may be required to eliminate tumors.Trial registration numberNCT03600350.
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