Data from Genomic Profiling of Metastatic Uveal Melanoma and Clinical Results of a Phase I Study of the Protein Kinase C Inhibitor AEB071

• DOI: 10.1158/1535-7163.c.6538543.v1
• Publication Date: 2023-04-03T20:50:06Z
• Authors: Sophie Piperno-Ne...; James Larkin; Richard D. Carvajal; Jason J. Luke; Gary K. Schwartz; F. Stephen Hodi; Marie-Paule Sablin; Alexander N. Shou...; Sebastian Szpakowski; Niladri Roy Chowd...; A. Rose Brannon; Thiruvamoor Ramkumar; Leanne de Koning; Adnan Derti; Caroline Emery; Padmaja Yerramill...; Ellen Kapiteijn
• Keywords: GNAQ; BAP1

<div>Abstract<p>Up to 50% of patients with uveal melanoma (UM) develop metastatic disease, for which there is no effective systemic treatment. This study aimed evaluate the safety and efficacy orally available protein kinase C inhibitor, AEB071, in UM, perform genomic profiling tumor samples, aim propose combination therapies. Patients UM (<i>n</i> = 153) were treated AEB071 a phase I, single-arm study. received total daily doses ranging from 450 1,400 mg. First-cycle dose-limiting toxicities observed 13 (13%). These most commonly gastrointestinal system dose related, occurring at ≥700 mg/day. Preliminary clinical activity was observed, 3% achieving partial response stable disease (median duration 15 weeks). High-depth, targeted next-generation DNA sequencing performed on 89 biopsy samples. Mutations previously identified including mutations <i>GNAQ, GNA11, BAP1, SF3B1, PLCB4</i>, amplification chromosome arm 8q. <i>GNAQ</i>/<i>GNA11</i> similar frequency (93%) as reported, confirming therapeutic window inhibition downstream effector PKC UM.</p><p>In conclusion, inhibitor well tolerated, modest UM. The findings consistent previous reports primary Together, our data allow envisaging therapies inhibitors other compounds UM.</p></div>