Do We Need KYC/AML: The Bank Secrecy Act and Virtual Currency Exchanges

Technology is moving faster than government or law can keep up. It\u27s moving faster than you can keep up: you should be asking the question of what are your rights and who owns your data. - Gus Hunt, 2013 CIA Chief Technology Officer1 The Currency and Foreign Transactions Reporting Act, commonly referred to as the Bank Secrecy Act (the BSA), is the U.S. government’s 800-pound gorilla when it comes to regulating virtual currency.2 It has been expanded, transformed, and updated since its initial passage in 1970 to keep pace with new developments in global terrorism and money laundering, all the while only being challenged twice on its constitutional merits.3 The BSA, as notably amended by the Uniting and Strengthening America by Providing Appropriate Tools Required to Intercept and Obstruct Terrorism Act of 2001 (USA PATRIOT Act), imposes financial recordkeeping and reporting requirements, know your customer (KYC) requirements, and requirements to implement and maintain an anti-money laundering (AML) program. 4 Noncompliance can lead to both civil money penalties of varying amounts and criminal penalties of up to twenty-years imprisonment.

Abstract OT1-08-01: A phase Ib trial of sequential combinations of BN-brachyury, entinostat, ado-trastuzumab emtansine (T-DM1) and bintrafusp alfa (M7824) in advanced stage breast cancer (BrEAsT)

Abstract Immune checkpoint blockade (ICB) monotherapy has produced limited benefit in breast cancer (BC) with response rates (RR) ranging from 5 to 23%. Combination ICB improved RR and progression free survival (PFS) resulting in atezolizumab + nab-paclitaxel receiving FDA accelerated approval for programmed cell death ligand 1 (PD-L1) positive, triple negative breast cancers (TNBC). BC has historically been considered immunologically quiet with most having a low mutational burden, low PD-L1 expression, defective antigen presentation machinery, and immuosuppressive signals in the tumor microenvironment (TME). An approach using a combination of immuno-oncology (IO) agents including ICB, immunomodulators and vaccines may shift the TME to allow for improved antigen presentation, the release of immunostimulatory cytokines, more immunogenic cell death and increased PD-L1 expression. The transcription factor brachyury plays an important role in breast tumor plasticity. High brachyury expression is associated with treatment resistance and a worse prognosis. Entinostat is a histone deacetylase inhibitor that has activity in multiple breast cancer subtypes. Preclinical data demonstrates entinostat upregulates MHC, enhances immune-mediated lysis and upregulates PD-L1 expression through epigenetic modification. Bintrafusp alfa is a bifunctional protein composed of the extracellular domain of the TGF-βRII receptor (TGF-β“trap”) fused to a human IgG1. Preclinical data shows bintrafusp alpha treatment increases T-cell trafficking, antigen-specific CD8+ T-cell lysis and NK cell activation. Monotherapy clinical studies with these agents have produced modest results in solid tumors, including BC. Preclinical data evaluating combinations of these agents shows a reduction in in tumor size, improved antigen-specific T-cell responses, reduced regulatory T cells, increased CD8+T-cells, and increased PD-L1 expression. We propose the stepwise addition of BN-Brachyury, Bintrafusp alfa, T-DM1 and Entinostat in advanced BC. This phase Ib study will assess efficacy and safety of the regimen and has three cohorts: Cohort 1(TNBC) will receive BN-Brachyury + Bintrafusp alfa. Cohort 2 (HER2+) will receive T-DM1 + BN-Brachyury + Bintrafusp alfa +/- entinostat. After safety is established in Cohort 2, patients in Cohort 3 (HER2+) will be assigned to receive T-DM1 + BN-Brachyury + Bintrafusp alfa +/- entinostat. Responses are evaluated every 2 cycles (6 weeks). Patients in Cohorts 2 and 3 will undergo research biopsies -baseline and after 2 cycles to evaluate changes within TME. Peripheral immune responses will be evaluated at selected time points. All patients must have measurable disease and HER2+ patients must have biopsiable disease. >1 prior treatment is required. Asymptomatic or brain metastases treated > 6 weeks are allowed. Well controlled HIV, HBV or treated HCV is allowed. Exclusion criteria include symptomatic brain metastases or clinically significant bleeding (<3 months from study entry). Co-primary objectives are RR and safety. Secondary objectives include PFS and changes in tumor infiltrating lymphocytes (Cohorts 2 and 3). Exploratory analyses include changes in immune cells and cytokines in the peripheral blood. Analyses performed will be descriptive, reporting the outcome measure for each treatment arm indicated along with two-tailed 80% and 95% confidence intervals. All cohorts employ a safety assessment in the initial 6 patients and a Simon minimax 2-stage design for clinical efficacy. We plan to recruit 51 patients: 13 patients with TNBC, 38 patients with HER2+BC. This trial will open Fall 2019 at the National Institutes of Health (Bethesda, MD). For more information contact the PI, [email protected]. Citation Format: Margaret E Gatti-Mays, Claudia Palena, Sofia R Gameiro, Renee N Donahue, Caroline Jochems, Seth Steinberg, Stan Lipkowitz, Alexandra Zimmer, Deneise Francis, Julius Strauss, Houssein Abdul Sater, Lisa Cordes, Jason Redman, Fatima Karzai, Marijo Bilusic, Ravi A Madan, James L Gulley, Jeffrey Schlom. A phase Ib trial of sequential combinations of BN-brachyury, entinostat, ado-trastuzumab emtansine (T-DM1) and bintrafusp alfa (M7824) in advanced stage breast cancer (BrEAsT) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT1-08-01