Phase II multicenter, open-label study of oral ENMD-2076 for the treatment of patients with advanced fibrolamellar carcinoma Journal Article
| Authors: | Abou-Alfa, G. K.; Mayer, R.; Venook, A. P.; O'Neill, A. F.; Beg, M. S.; LaQuaglia, M.; Kingham, P. T.; Kobos, R.; Basturk, O.; Brennan, C.; Yopp, A.; Harding, J. J.; Leong, S.; Crown, J.; Hoti, E.; Leonard, G.; Ly, M.; Bradley, M.; Valentino, E.; Markowitz, D.; Zukiwski, A.; Ren, K.; Gordan, J. D. |
| Article Title: | Phase II multicenter, open-label study of oral ENMD-2076 for the treatment of patients with advanced fibrolamellar carcinoma |
| Abstract: | 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. © AlphaMed Press; the data published online to support this summary is the property of the authors. |
| Journal Title: | The Oncologist |
| Volume: | 25 |
| Issue: | 12 |
| ISSN: | 1083-7159 |
| Publisher: | Oxford University Press |
| Date Published: | 2020-12-01 |
| Start Page: | e1837 |
| End Page: | e1845 |
| Language: | English |
| DOI: | 10.1634/theoncologist.2020-0093 |
| PUBMED: | 32154962 |
| PROVIDER: | scopus |
| PMCID: | PMC8186410 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 4 January 2021 -- Source: Scopus |
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