LESSONS LEARNED: The fibrolamellar carcinoma-associated DNAJB1-PRKACA gene 
fusion transcript RNA codes for the catalytic domain of protein kinase A and, 
thus, overexpression of Aurora kinase A. ENMD-2076 showed a favorable toxicity 
profile. The limited results, one patient (3%) with a partial response and 57% 
of patients with stable disease, do not support further evaluation of ENMD-2076 
as single agent. Future studies will depend on the simultaneous targeting 
approach of DNAJB1-PRKACA and the critical downstream components.
BACKGROUND: Fibrolamellar carcinoma (FLC) represents approximately 0.85% of 
liver cancers. The associated DNAJB1-PRKACA gene fusion transcript RNA codes for 
the catalytic domain of protein kinase A and overexpression of Aurora kinase A 
(AURKA). ENMD-2076 is a selective anti-AURKA inhibitor.
METHODS: Patients aged >12 years with pathologically confirmed incurable FLC, 
with measurable disease, Eastern Cooperative Oncology Group performance status 
0-2 or Lansky 70-100, and adequate organ function were eligible. Patients were 
prescribed ENMD-2076 based on body surface area. The primary endpoint was 
overall objective response rate by RECIST v1.1, with a null hypothesis of true 
response rate of 2% versus one-sided alternative of 15%. Secondary endpoints 
included 6-month progression-free survival (PFS) rate (Fig. 1), median PFS, time 
to progression (TTP), and overall survival (OS). Safety was evaluated throughout 
the study.
RESULTS: Of 35 patients who enrolled and received treatment, 1 (3%) had a 
partial response (PR) and 20 (57%) had stable disease (SD). Median TTP, PFS, and 
OS were 5, 3.9, and 19 months, respectively. The most frequently reported 
drug-related serious adverse event was hypertension in three patients. Three 
deaths were reported on-study-two due to disease progression and one due to 
pulmonary embolism not related to ENMD-2076.
CONCLUSION: The study provided no rationale for further studying ENMD-2076 as a 
single agent in FLC.