Navarro, Shannon M.

e16200 Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Indoleamine-2,3-dioxygenase (IDO) is an intracellular enzyme expressed by HCC which helps to orchestrate immune suppression within the tumor microenvironment (TME) and may contribute to primary and acquired resistance of PD-(L)1 inhibitors. BMS-986205 is a novel oral drug that potently and selectively inhibits IDO1. This Phase I/II study is evaluating the safety and tolerability of the combination of BMS-986205 and nivolumab as first-line therapy in HCC. Methods: Patients (pts) ≥18y with untreated, unresectable/metastatic HCC received BMS-986205 in combination with nivolumab. A fixed dose of Nivolumab 240mg/m2 IV was administered on Day 1 of each 14-day cycle. BMS-986205 was an oral tablet administered daily; a total of two dose levels (50-100mg) were given to determine dose limiting toxicities (DLT) during the dose-escalation Phase I of the study. Safety was assessed using CTCAE v5.0 criteria, and efficacy was assessed by objective response rate (ORR) using RECIST v1.1 criteria. Secondary objectives included preliminary data on disease control rate (DCR), duration of response (DOR), ORR using immune RECIST criteria (iRECIST), progression free survival (PFS) and overall survival (OS). Results: Here we report the results of the dose escalation cohort. Eight pts were treated with median age 69y [60-76]; 75% male; and PS 0 (3 pts) or 1 (5 pts). Pts were White (62.5%), Asian (25%), and African American (12.5%). Six of 8 pts had underlying viral hepatitis (5 hepatitis C, 1 hepatitis B), and all pts were Child Pugh A at enrollment with median baseline alpha-fetoprotein (AFP) level 41.8 [3.8–917.2]; 4 pts received prior local therapies. A total of 91 cycles of therapy were administered; 2 pts received 27 and 43 cycles of treatment each. Six pts were evaluable for DLT; 2 pts were replaced for DLT assessment due to insufficient dose administered, unrelated to toxicity. No DLTs were observed at either the 50 or 100mg dose of BMS-986205. There were 24 treatment-related adverse events (TRAEs), 4 of which were Grade 3 events; there were no Grade 4-5 events. The most common TRAEs of all grades were AST elevation and ALT elevation in 3 pts, and diarrhea, maculopapular rash and increased alkaline phosphatase in 2 pts each. Grade 3 events were diarrhea and AST elevation (1 pt), and hyperglycemia and pancreatitis requiring treatment discontinuation (1 pt). Eight pts were evaluable for efficacy with best response of partial response in 1 pt (12.5%) and stable disease in 3 pts (37.5%), yielding a DCR of 50%. Median PFS was 8.5 weeks; median OS has not been reached. Conclusions: Combination BMS-986205 and nivolumab showed a manageable safety profile with durable benefit as 1st line therapy in a meaningful subset of patients with unresectable/metastatic HCC. Clinical trial information: NCT03695250.

ObjectivesTo evaluate the effectiveness of templated ultrasound reports using transplant renal artery stenosis (TRAS) risk stratification (RS), particularly with regard to utilization of downstream angiographic studies and angiographic presence of TRAS.MethodsUltrasounds with TRAS‐RS templated reports from August 2017 to May 2020 were included. Studies were excluded if performed <28 days posttransplant and where TRAS was not clinically considered. A total of 530 ultrasounds met inclusion/exclusion criteria. TRAS‐RS criteria were recorded (renal artery velocity ≥300 cm/s, spectral broadening in the renal artery, and intraparenchymal acceleration time ≥0.1 second). Depending on the number of criteria present, recipients were stratified into low (0/3), intermediate (1/3), high (2/3), and very high (3/3) risk for TRAS. Student's t‐test was performed to identify whether the TRAS‐RS category was associated with 1) performance of angiography to assess for TRAS and 2) angiographic presence of TRAS.ResultsOf the 530 ultrasounds, 74 (14%) underwent angiography. Of these, 41 (55%) were positive for TRAS (overall positive rate, 8%). Number of ultrasounds, angiograms, and angiograms positive for TRAS, respectively, in each of the TRAS‐RS categories for the 530 cases were: low probability: n = 370 (70% of all studied reports), 7 angiograms (2%), and 0 (0%) positive for TRAS; intermediate: n = 87 (16%), 24 angiograms (28%), and 8 (33%) positive; high: n = 46 (9%), 23 angiograms (50%), and 14 (61%) positive; and very high: n = 27 (5%), 20 angiograms (74%), and 19 (95%) positive. TRAS‐RS score was associated with subsequent performance of angiography and positive rate for TRAS (P < .01).ConclusionImplementing a defined ultrasound screening tool with templated reporting for TRAS allowed for effective selection of those requiring an angiogram.