Abstract CT096: Phase I study of in situ autologous vaccination for prostate cancer in a neo-adjuvant setting
Authors: Nair Sujit S. , Weil Rachel , Gonzalez-Gugel Elena , Meseck Marcia , Rubinsteyn Alex , Kodysh Yulia , Gupta Akriti , Sadanala Keerthi , Schlussel Kacie , Bhatt Kamala , Reddy Avinash , Patel Rajan , Thawte Tin , Farkas Adam , Dzedzik Siarhei , Haines Kenneth , Wagner Julia , Robison Macy , Knauer Cynthia , Salazar Andres , Galsky Matthew , Bhardwaj Nina , Tewari Ashutosh 
Published: August 2019

Abstract
Background:
Certain solid malignancies like prostate cancer pose two major challenges for effective immunotherapy. The inherently low mutation load and spatial and temporal intra-tumor heterogeneity yields an immune exclusion and development of an “immune desert” within the tumor micro-environment (TME). Additionally, there is a response failure to immunomodulation, due to tumor/patient immunosuppressive mechanisms. In an effort to transform the prostate tumor environment into an immunogenic ecosystem, we are using PolyIC:LC as an immunemodulator. The novelty of this approach is a “host targeted”, in-situ “autovaccination” strategy, which uses the patient’s own tumor as the antigen source leading to activation of both an innate and adaptive immune response. As all patients will have their cancer removed after investigational therapy we can study baseline versus treatment induced changes in bio-specimens collected before, during, and after patients are exposed to PolyIC:LC. Correlative studies include characterization of tissue and systemic biomarkers of response using multiple platforms like cytometry by time of flight (CyTOF), RNA-seq, whole exome sequencing, seromics, TCR-sequencing, neoantigen specific T-cell responses, as well as assessing circulating tumor DNA (ctDNA) at multiple time points to determine the potential in detecting tumor response to immunemodulation.
Methods:
This is a Phase I dose escalation study (NCT03262103) seeking to determine a safe dose and schedule of intratumoral (IT) plus intramuscular (IM) PolyIC:LC injections prior to radical prostatectomy in patients with prostate cancer. The dose and frequency of IT PolyIC:LC will be increased in successive cohorts using a 3+3 design and traditional dose escalation rules. The dose and schedule of IM PolyIC:LC will remain fixed in successive cohorts. The study will consist of 24 enrolled subjects, recruited into cohorts consisting of a minimum of 3 and maximum of 6 patients per cohort. The first cohort, consisting of three patients, has been completed. Recruitment for the second cohort has begun with two patients already enrolled. The inclusion criteria extend to patients diagnosed with high risk (Gleason 7-10, cT2a-cT3b) clinically localized prostate cancer with no prior hormonal or radiation therapy and with plans to undergo radical prostatectomy. Week 1 serves as the priming course with the patient coming in for a pre-treatment biopsy followed by an IT injection. Weeks 3-6 consist of a booster treatment course with IM injections two times a week. Weeks 7-9 are a rest period with no injections followed by radical prostatectomy at week 10. Blood is drawn at weeks 1, 3, 6, and 9. At the time of surgery, blood, tissue, and lymph node are collected for research purposes. Following each IT and IM injection, the subject remains in clinic for monitoring for at least 1 hour or 30 minutes respectively. Patients are seen 6 weeks post-prostatectomy as per standard of care. The next follow-up visit is approximately 3 months following surgery where the first post-operative PSA check is performed. Assuming PSA levels are undetectable, the patient is followed up at routine intervals for PSA testing.
Citation Format: Sujit S. Nair, Rachel Weil, Elena Gonzalez-Gugel, Marcia Meseck, Alex Rubinsteyn, Yulia Kodysh, Akriti Gupta, Keerthi Sadanala, Kacie Schlussel, Kamala Bhatt, Avinash Reddy, Rajan Patel, Tin Thawte, Adam Farkas, Siarhei Dzedzik, Kenneth Haines, Julia Wagner, Macy Robison, Cynthia Knauer, Andres Salazar, Matthew Galsky, Nina Bhardwaj, Ashutosh Tewari. Phase I study of in situ autologous vaccination for prostate cancer in a neo-adjuvant setting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT096.