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
3128 - Systemic bevacizumab for the treatment of recurrent respiratory papillomatosis: A retrospective analysis from an academic tertiary care center
Presenter: Sumita Trivedi
Session: Poster Display session 3
Resources:
Abstract
1242 - Monalizumab in combination with cetuximab in patients (pts) with recurrent or metastatic (R/M) head and neck cancer (SCCHN) previously treated or not with PD-(L)1 inhibitors (IO): 1-year survival data.
Presenter: Roger Cohen
Session: Poster Display session 3
Resources:
Abstract
4703 - Updated results of a phase II study evaluating accelerator-based boron neutron capture therapy (AB-BNCT) with borofalan(10B) (SPM-011) in recurrent squamous cell carcinoma (R-SCC-HN) and recurrent and locally advanced non-SCC (R/LA-nSCC-HN) of the head and neck
Presenter: Katsumi Hirose
Session: Poster Display session 3
Resources:
Abstract
3638 - Phase 3 KEYNOTE-048 Study of First-Line (1L) Pembrolizumab (P) for Recurrent/Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC): Asia vs Non-Asia Subgroup (subgrp) Analysis
Presenter: Makoto Tahara
Session: Poster Display session 3
Resources:
Abstract
2954 - Integrated data review evaluating safety, pharmacokinetics (PK) and immunogenicity of RM-1929 photoimmunotherapy (PIT) in subjects with locoregional, recurrent head and neck squamous cell carcinoma (rHNSCC).
Presenter: Jennifer Johnson
Session: Poster Display session 3
Resources:
Abstract
3629 - First line versus second line immunotherapy in recurrent/metastatic squamous cell carcinoma of the head and neck
Presenter: Caroline Even
Session: Poster Display session 3
Resources:
Abstract
767 - Sensitizing HRAS overexpressing head and neck squamous cell carcinoma (HNSCC) to chemotherapy
Presenter: Theodoros Rampias
Session: Poster Display session 3
Resources:
Abstract
4985 - A Single-Arm, Open-Label, Multicenter, Phase IIIb Clinical Trial with Nivolumab in Subjects with Recurrent or Metastatic Platinum-refractory Squamous Cell Carcinoma of the Head and Neck.
Presenter: Paolo Bossi
Session: Poster Display session 3
Resources:
Abstract
1564 - Long-term Results of Phase 2 Trial of Reduced Modified Clinical Target Volume in Low-risk Nasopharyngeal Carcinoma Treated with Intensity Modulated Radiotherapy
Presenter: Jingjing Miao
Session: Poster Display session 3
Resources:
Abstract
3356 - To compare two oral mucosa contouring methods in predicting acute oral mucocitis in nasopharyngeal carcinoma treated with helical tomotherapy
Presenter: Yuan-Yuan Chen
Session: Poster Display session 3
Resources:
Abstract