A novel patient-centric longitudinal data registry platform to generate insights into real-world cholangiocarcinoma (CCA) clinical practice.

person Amanda Nottke Invitae, San Francisco, CA info_outline Amanda Nottke, Milind M. Javle, Mitesh J. Borad, Nilofer Saba Azad, Elise Brimble, Richard L Martin, Conner OBrien, Stacie Lindsey, Melinda Bachini, Shishir K. Maithel

Authors person Amanda Nottke Invitae, San Francisco, CA info_outline Amanda Nottke, Milind M. Javle, Mitesh J. Borad, Nilofer Saba Azad, Elise Brimble, Richard L Martin, Conner OBrien, Stacie Lindsey, Melinda Bachini, Shishir K. Maithel Organizations Invitae, San Francisco, CA, The University of Texas MD Anderson Cancer Center, Houston, TX, Mayo Clinic Arizona, Scottsdale, AZ, Johns Hopkins University, Chevy Chase, MD, Cholangiocarcinoma Foundation, Salt Lake City, UT, Winship Cancer Center of Emory University, Atlanta, GA Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Invitae Corporation Background: Treatment of advanced CCA has changed dramatically over the past five years with the advent of molecularly targeted therapy, now approved in the 2nd line and beyond. However, real world utilization of molecular profiling and targeted therapy is still unknown and these data are critical to empower treatment decision-making. Methods: In 2019, the Cholangiocarcinoma Foundation (CCF) and Ciitizen (a wholly owned subsidiary of Invitae Corporation) collaboratively launched a registry platform that directly consents patients and collects comprehensive medical records. De-identified data including clinical characteristics, molecular testing, interventions, and outcomes are extracted and standardized for research use. The data is longitudinal with regularly planned updates; registry participants can be re-engaged to obtain additional data and communicate tailored insights. Results: We quantified the rate of molecular testing, the presence of targetable biomarkers, and the utilization and outcomes on matched targeted therapies for 372 individuals with CCA. 328 (88.2%) individuals had molecular testing, with the identified targetable mutations and matched therapies reported. Of 328 individuals who had molecular testing, 111 (33.8%) individuals had one or more targetable mutations (116 mutations total). Only 46% (51) of individuals with targetable mutations received targeted therapy. Of the 54% (60) individuals with targetable mutations that did not receive any matched therapy, the majority (61.7%, 37) were in early disease or first line of treatment and therefore not yet eligible for targeted therapy. These individuals will be informed that based on their molecular profile, a targeted therapy may be an option, and suggest they discuss with their treating physician. Conclusions: A novel prospectively-maintained database registry for CCA has been formed in collaboration between a patient advocacy organization (CCF) and industry (Invitae). Prevalence of actionable biomarkers was higher than historically expected and may reflect patient utilization bias of the registry platform. Molecular profiling and access to targeted therapeutics remains suboptimal at this time in CCA. Future directions for the registry include identifying and targeting disparities in care and supporting biopharmaceutical development and regulatory decisions. Biomarker Evaluable Cohort (n=328) # (%) # Not Receiving Matched Therapy # Receiving Matched Therapy Matched Therapy Outcomes (mean no. days; #) IDH1 R132 45 (13.7%) 28 17 ToT: 190 (16) TtP: 158 (9) FGFR2 Fusion / Rearrangement 34 (10.4%) 15 19 ToT: 319.4 (19) TtP: 367.5 (10) MSI-H / dMMR / TMB-H 25 (7.6%) 12 13 ToT: 368.4 (13) TtP: 210.6 (5) HER2 Positive / Amplified 9 (2.7%) 7 2 ToT: 219 (2) TtP: 499.5 (2) BRAF V600E 3 (0.9%) 2 1 ToT: 32 (n=1) TtP: 114 (n=1) ToT: Time on Treatment; TtP: Time to Progression.