Roadmap for Immunotherapy in Genitourinary Cancers
Aims and Focus of Program
1. Combination Immunotherapy- Efficacy of Immunotherapy with standard of care therapies
2. Neo-adjuvant immunotherapy for early and clinically localized Prostate Cancer
3. Racial disparity and impact of immune countermeasures in cancer
4. Immunotherapy for prostate cancer patients with biochemical recurrence
Ongoing Clinical Trials-(Recruiting)
1. Phase 1 Study of In Situ Augologous Vaccination Against Prostate Cancer with Intratumoral and Systemic Hiltonol® (Poly-ICLC) Prior to Radical Prostatectomy. Clinical Trial # NCT03262103
2. Kite-718-301: A Phase 1 Study Evaluating the Safety and Efficacy of MAGE-A3/A6 T Cell Receptor Engineered T Cell (KITE-718) in HLA-DPB1*04:01Positive Subjects with Advanced Cancers. Clinical Trial # NCT03139370
Suppression of immune responses is a hallmark of cancer and innovative immunotherapy strategies that can effectively manipulate and counteract immunosuppressive mechanisms are changing clinical practice. Despite the feasibility and promise of such approaches, certain solid malignancies like prostate cancer pose two major challenges for successful immunotherapy. First, the biology and tumor microenvironment is unique such that it can result in exclusion of immune cells. Second, the diverse and biologically heterogeneous nature of the tumor and the immune response that differs between individuals makes it difficult to readily stratify patients into responder and non-responder populations. To overcome these major challenges we have embarked upon a novel immunotherapy strategies that can convert the prostate tumor to an immune favorable ecosystem and in doing so identify biomarkers that can accurately identify patients who will receive clinical benefit. We propose several new approaches in prostate cancer patients who are at high risk of recurrence to change the tumor microenvironment and determine what parameters in the tumor and blood can be correlative biomarkers of an immune response. These biomarkers will aid us in stratifying what patients will benefit from this type of therapy. From other studies we have found that this approach, which involves injecting an immune modulator into the tumor bed, can dramatically change the tumor environment. Predictive biomarkers will enable prospective identification of patients who are most likely to respond to immunotherapy and has the potential to eventually define disease progression, predict relapse and enable rationale design of combination therapies for high-risk patients
Utilizing multidimensional platforms, our long-term goal is to develop mechanism-based robust biomarkers with high clinical specificity and utility that can be used in future immune monitoring programs. Our expected contribution is proof of concept that correlative biomarkers of immune response can predict success or failure of immunotherapy very early on. Immediate application of our research is that immunophenotyping of patients based on multimodal biomarkers can avoid adverse events, and significant treatment costs for patients who are not likely to benefit from immunotherapy. In patients who are eligible and receive immunotherapy, correlative studies with clinical endpoints like time to relapse, time to recurrence and progression can used to determine the impact of treatment and the extent of response. Utilizing this approach, we expect to develop a new ability to identify high-risk cancer-immune phenotypes among patients including non-responders or patients who initially respond and develop resistance, and map them to appropriate second-line treatments like combination therapy (eg. checkpoint inhibitors) or personalized immunotherapy treatment regimens (personalized peptide vaccine). Upon completion of this proposal we expect to have generated unparalleled data that can be used to identify eligible patients for immunotherapy in larger patient cohorts or within high risk ethnic minority or racial populations (African American). Our research is not standard of care however due to high clinical significance multimodal biomarkers has potential to become mainstay in clinical trials of immunotherapy and improve standard of care. Prospective identification of patients could possibly alter need for life changing surgery and improve quality of life (like BCG does).
Patients and advocate groups have an active role in medical research. The Tisch Cancer Institute at Mount Sinai, an NCI designated cancer center is a research site for Hoosier Cancer Research Network (HCRN), a non-profit organization that specializes in contract research for investigator initiated clinical trials. Through collaborative research agreements we will involve HCRN advocates at an early stage for implementation of study protocol as well as validation and dissemination study results by means of peer-reviewed publications, e-news reports or educational webinars within the widespread HCRN network. Through this productive collaborative experience, we expect to a) communicate scientific information to scientific and non-scientific audiences and b) accrue patients for the ongoing and future Phase-II portion of the trial. The Prostate Cancer Foundation (PCF) collaborates and provides support to multiple research initiatives within the Department of Urology and Icahn School of medicine. Ongoing and completed studies will be presented at Annual PCF meetings or shared via weekly webinars. We further plan to disseminate the highlights, ongoing progress and study outcomes through educational sessions, mini-symposiums or poster presentations at the annual meetings of cancer advocate groups like American Urological Association, American Cancer Society, American Association for Cancer Research and National Comprehensive Cancer Network. We will work closely with additional non-profit organizations such as the Cancer Hope Network, Cancer Support Community and ZERO-the end of prostate cancer to translate scientific information of the study to a larger patient community.