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
1084 - Dissociated responses in patients with metastatic solid tumors treated with immunotherapy
Presenter: Pauline Vaflard
Session: Poster Display session 3
Resources:
Abstract
4600 - Patterns and outcomes related to rapid progressive disease in a cohort of advanced solid tumors treated with immune checkpoint inhibitors (ICIs).
Presenter: Lucio Ghiglione
Session: Poster Display session 3
Resources:
Abstract
3547 - Real World Outcomes of Immune-Related Adverse Events (irAEs) among Patients Receiving Immune Checkpoint Inhibitors (ICIs) in Hospital Settings
Presenter: Saby George
Session: Poster Display session 3
Resources:
Abstract
1124 - Sex-based heterogeneity of efficacy of anticancer immunotherapy
Presenter: Fabio Conforti
Session: Poster Display session 3
Resources:
Abstract
4133 - Comparative efficacy and safety of PD-1/PD-L1 inhibitors for patients with solid tumors: a systematic review and Bayesian network meta-analysis
Presenter: Qingyuan Huang
Session: Poster Display session 3
Resources:
Abstract
2548 - Excess weight and efficacy of anti-PD-1 antibodies in advanced cancer patients
Presenter: Jacobo Rogado
Session: Poster Display session 3
Resources:
Abstract
2228 - Safety and efficacy of anti-PD-1 inhibitor ABBV-181 in lung and head and neck carcinoma
Presenter: Antoine Italiano
Session: Poster Display session 3
Resources:
Abstract
2333 - Efficacy and safety of immune checkpoint inhibitors (ICIs) for treatment of advanced solid tumours in octogenarian patients
Presenter: Soraya Mebarki
Session: Poster Display session 3
Resources:
Abstract
4847 - Association of programmed cell death 1 (PD-1) inhibitor therapy with overall survival (OS) in stage IV melanoma treated with targeted therapies
Presenter: Aracelis Torres
Session: Poster Display session 3
Resources:
Abstract
2215 - Clinical outcomes of immune checkpoint inhibitors in older and younger patients with advanced solid tumours in a real-life setting
Presenter: Pauline Corbaux
Session: Poster Display session 3
Resources:
Abstract