Abstract 2492
Background
Therapeutic cancer vaccines targeting tumour associated antigens (TAAs) offer a potential method to activate cytotoxic T-cells. A vaccine using a novel Ad5 vector (E1-, E2b-) targeting 3 TAAs, PSA, MUC-1 and Brachyury, has been constructed. Both the C-terminus of MUC-1 and Brachyury have been shown to play an integral role in epithelial-to-mesenchymal transition, metastasis, and chemotherapy resistance. Both antigens are overexpressed in mCRPC. The transgenes for PSA, MUC-1 and Brachyury contain modifications for the expression of CD8+ T-cell enhancer agonist epitopes. This vaccine has not been previously tested in humans.
Methods
Pts with mCRPC were treated with the combination of 3 vaccines targeting PSA, MUC-1 and Brachyury at 5 x 1011 viral particles (VP) each, SQ every 3 weeks for maximum of 3 doses (dose de-escalation cohort) and followed by boost every 8 weeks for 1 year (dose expansion cohort only). The primary objective was to determine the safety and tolerability and to establish the recommended phase 2 dose. Immune assays were conducted in the first 5 enrolled patients.
Results
12 pts were enrolled (6 in each cohort) between 07/2018 and 04/2019 and received at least 1 dose. Median PSA was 37.8 (range, 5.81 – 1006 ng/mL). Vaccine was safe and tolerable, no DLTs or grade 3 or higher treatment-related adverse events (TRAEs) were observed. All other TRAEs were Grade 1 or 2; the most common was injection-site reaction in all pts. Two chemotherapy naïve pts had confirmed PSA declines (89% and 50%, respectively) observed after only 1 dose. Third had unconfirmed 12% PSA decline at week 3. 5/5 patients mounted responses to at least 1 TAA while 3/5 mounted immune responses to all 3 TAAs. Multifunctional T-cell responses to PSA, MUC-1 and Brachyury were also detected post-vaccination.
Conclusions
Ad5 PSA/MUC-1/Brachyury vaccine is safe and well tolerated. The recommended Phase 2 dose is 5 x 1011 VP. Confirmed PSA decline was observed in 2 pts. Multifunctional TAA specific T-cell responses to all 3 antigens were seen in a patient with 89% PSA decline. Further research is warranted to evaluate immunogenicity and eventual clinical benefit. Future trials will involve the use of this vaccine in combination with other immuno-oncology agents.
Clinical trial identification
NCT03481816.
Editorial acknowledgement
Debra Weingarten.
Legal entity responsible for the study
Center for Cancer Research, National Cancer Institute, National Institutes of Health.
Funding
Intramural Research Program of the Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), and by Cooperative Research and Development Agreements (CRADAs) between the NCI and NantCell/Etubics, and the NCI and NantBioscience.
Disclosure
E.S. Gabitzsch: Full / Part-time employment: Etubics Corporation. F.R. Jones: Full / Part-time employment: Etubics Corporation. J.P. Balint: Full / Part-time employment: Etubics Corporation. P. Soon-Shiong: Full / Part-time employment, Founder and an executive: NantCell; Full / Part-time employment, Founder and an executive: NantBioscience. S. Rabizadeh: Full / Part-time employment: NantCell. All other authors have declared no conflicts of interest.
Resources from the same session
2344 - Lung Cancer in Europe: strengthening policy responses to address unmet needs
Presenter: Mary Bussell
Session: Poster Display session 3
Resources:
Abstract
1359 - Curative treatment timelines for breast, colorectal, lung and prostate cancer: Implications for medical leave coverage
Presenter: Selina Wong
Session: Poster Display session 3
Resources:
Abstract
4433 - Acute Diagnostic Oncology Clinic: A Unique Primary Care-Oncology Service
Presenter: Abhijit Gill
Session: Poster Display session 3
Resources:
Abstract
3506 - THE NEW MUTATIONAL MODEL IN ONCOLOGY. What changes in welfare, clinical practice, research, and regulatory procedures
Presenter: Nicola Normanno
Session: Poster Display session 3
Resources:
Abstract
3350 - Selection of a set of quality indicators (QI) for oncological clinical pathway
Presenter: Aude Fourcade
Session: Poster Display session 3
Resources:
Abstract
4400 - Sustainable drug prices at market launch: policy proposals and their empirical evidence
Presenter: Nora Fanzen
Session: Poster Display session 3
Resources:
Abstract
4118 - Impact of financial considerations on French physicians’ prescription choices for advanced non-small cell lung cancer (NSCLC)
Presenter: Nathalie Olympios
Session: Poster Display session 3
Resources:
Abstract
1340 - The direct medical cost of breast cancer in a Belgian hospital
Presenter: Hannan Lemhouer
Session: Poster Display session 3
Resources:
Abstract
1863 - Does the healthcare system approaches cancer patients for using private services during diagnostic process?
Presenter: Karolina Osowiecka
Session: Poster Display session 3
Resources:
Abstract
2637 - Measuring financial toxicity of cancer in the Italian health care system: initial results of the patient reported outcome for Fighting Financial Toxicity of cancer project (proFFiT).
Presenter: Silvia Riva
Session: Poster Display session 3
Resources:
Abstract