Background: The Prostate Cancer Research Program at Weill Cornell Medicine (WCM) and New York-Presbyterian (NYP) is an internationally recognized prostate cancer (PC) clinical and translational research program. In 2017, we were awarded a Specialized Programs of Research Excellence (SPORE) grant in PC, highlighting the depth and breadth of our research. Since joining the Prostate Cancer Clinical Trials Consortium (PCCTC) as a Clinical Research Site in 2014, WCM has brought multiple high-impact and innovative therapeutic and biomarker studies to the PCCTC; enrolled more than 100 patients in clinical trials, including 56 this past year; collected, processed, and analyzed over 500 tumor biopsy specimens, circulating tumor cells, and plasma and serum samples in a regulatory-compliant manner; complied with consortium-developed quality assurance and quality control procedures; and led PC advocacy initiatives within the PCCTC. We are expanding our site to include NYP Brooklyn Methodist Hospital (NYPBMH) and Columbia University Medical Center (CUMC).
Objective/Hypothesis: The objective of this proposal is for WCM, together with NYPBMH and CUMC, to participate in the PCCTC as a multi-site Clinical Research Site. Our overall aim is to translate our PC expertise in targeted therapies, PC imaging, immunotherapy, and correlative science into novel therapeutic approaches that can be tested in multi-institutional studies performed within the PCCTC. We intend to bring novel agents and new biomarker-driven trials directly to PC patients, including underrepresented minorities.
1. Develop and study novel, targeted therapeutics identified through high-quality molecular analyses.
2. Identify effective treatments and biomarkers based on discovery of mechanisms of PC therapy resistance and sensitivity.
3. Advance PC immunotherapeutics based on pre-clinical investigations.
4. Study PSMA-targeted radionuclide therapy and develop PSMA molecular imaging.
5. Open up PCCTC studies to underrepresented minorities in Brooklyn and Upper Manhattan.
Study Design: We have a well-balanced portfolio of therapeutics and molecular diagnostics, with a robust pipeline of agents and new concepts. Planned Phase I/II clinical trials or correlative studies to be conducted within the PCCTC include (1) PSMA-targeted studies of beta (177Lu-PSMA-617 and 177Lu-J591) and alpha radionuclides (225Ac-J591); (2) antibody-drug conjugate targeting Delta-like protein 3 expressed on NEPC with rovalpituzumab tesirine; (3) antibody-drug conjugate targeting Trop-2 expressed on PC with sacituzumab govitecan; (4) combination immunotherapy affecting multiple immune pathways (PD-1 inhibition using nivolumab and NK activation using elotuzumab); (5) B7-H3/CD3 bispecific antibody MGA-271 to facilitate T-cell trafficking to primary PCs; (6) epigenetic therapy using the anti-EZH2 inhibitor, GSK126; (7) PSMA imaging using novel PSMA ligands; (8) androgen receptor/microtubule pathway targeted by combination agents (taxane, CYP17 inhibitor, and AR signaling inhibitor, ARN-509), including biomarkers, novel taxanes, CTC, and ctDNA analyses to predict treatment response; and (9) circulating tumor DNA (ctDNA) analysis using the PCF SELECT platform. In addition, drugs are currently in development at our Tri-I Target-Discovery Institute to target AR-v7 splice variant and N-myc-Aurora A (for NEPC). We will engage and recruit underrepresented minorities to PCCTC studies by incorporating NYPBMH and CUMC into the current WCM Clinical Research Site.
Clinical Impact: Our team has a strong track record in clinical and translational research, with the expertise and resources necessary to directly impact and improve care of PC patients. We will treat these patients with targeted therapies and immunotherapies based on scientific discoveries; develop novel imaging platforms to detect PC; and incorporate into our clinical trials laboratory-based investigations of biomarkers for risk assessment and prediction of PC aggressiveness, progression, and treatment outcome. We will directly improve the health of African American and Hispanic men with PC by enrolling them in PCCTC clinical trials. Each of our treatment and diagnostic approaches has the potential to forcefully impact clinical management and improve outcomes for men with this disease.