Abstract CT053: High rates of personalized molecular matching are achievable in a precision oncology navigation trial: the I-PREDICT study
Authors: Sicklick Jason K. , Leyland-Jones Brian , Kato Shumei , Williams Casey , De Pradip , Heestand Gregory , Plaxe Steven , Solomon Benjamin , Miller Vincent , Benson Adam , Webster Jennifer , Ross Jeffrey , Scur Michael , Porter Robert , Jepperson Shelby , Fanta Paul , Kurzrock Razelle 
Published: July 2017

Abstract
Precision medicine has evolved as an individualized approach for treating cancer patients and has become standard in an ever-increasing number of clinical settings. It is predicated upon matching targeted-/immuno-therapy to genomic alterations detected in patients' tumors. However, widespread feasibility/adoption has been limited by: 1) high rates of insufficient tumor DNA (reaching 25%); 2) panels limited to few genes that are unable to detect multiple classes of genomic alterations; 3) testing patients late in the disease course; and 4) low molecular matching rates, which may be in part due to limited access to trials and the unpredictable nature of genomic alterations detected in each individual. We evaluated the feasibility of investigating molecular profile-related evidence for determining individualized cancer therapy (I-PREDICT) in patients with lethal tumors (NCT02534675). This navigation trial was performed under the auspices of 2 precision medicine programs (UCSD and Avera Cancer Institute) and an IRB-approved protocol. Treatment-naïve and previously treated patients with ECOG &lt;2 and metastatic/unresectable malignancies were eligible if their cancer was associated with ≥50% mortality risk at 2 years. Patients’ tumors underwent comprehensive genomic profiling (CGP, Foundation Medicine; ≥315 genes), PD-(L)1 immunostaining, assessment of microsatellite instability, tumor mutational burden and circulating tumor DNA analyses (CLIA certified CAP-accredited laboratory). A molecular tumor board discussed results immediately upon receipt, and provided recommendations, emphasizing customized combinations, for the use of FDA-approved or experimental therapeutics. Final management decisions were at the treating physician’s discretion.To date, 135 patients have enrolled (2/2015-10/2016). CGP was evaluable in 107 participants (79.3%). In 5 patients (3.7%), the tumor sample was inadequate for CGP. The other 23 patients were excluded due to screen failure or dropout. All 107 tumors had ≥1 (in)activating genomic alterations (median 4, range: 1-20; variants of unknown significance excluded). Of the 135 participants, 81 (60%) were treated; 63 (46.7% of enrollees) received matched therapy. There are 19 (14.1%) patients currently awaiting CGP results or medications, while 14 (10.4%) patients received only best supportive care before death. Sixty-two of the 81 (76.5%) patients treated have had ≥1-restaging scan to date.With the use of more comprehensive DNA panels, inclusion of patients earlier in their disease course, just-in-time molecular tumor board discussions, and increasing availability of cognate drugs, we report: 1) low rates of inevaluable tumor tissue ( &lt;5%); 2) high detection rates of ≥1 (in)activating alterations (100% with evaluable CGP); and 3) high molecular matching rates (approaching 50%). Response and survival assessments are ongoing.
Citation Format: Jason K. Sicklick, Brian Leyland-Jones, Shumei Kato, Casey Williams, Pradip De, Gregory Heestand, Steven Plaxe, Benjamin Solomon, Vincent Miller, Adam Benson, Jennifer Webster, Jeffrey Ross, Michael Scur, Robert Porter, Shelby Jepperson, Paul Fanta, Razelle Kurzrock. High rates of personalized molecular matching are achievable in a precision oncology navigation trial: the I-PREDICT study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT053. doi:10.1158/1538-7445.AM2017-CT053