A phase 1b/2 study of amcasertib, a first-in-class cancer stemness kinase inhibitor, in advanced adenoid cystic carcinoma.

Abstract

6036 Background: Amcasertib (BBI-503) is an oral first-in-class cancer stemness kinase inhibitor. By targeting multiple serine-threonine stemness kinases, amcasertib inhibits Nanog and other cancer stemness pathways. A phase I clinical trial of amcasertib demonstrated safety and signs of anti-cancer activity in patients (pts) with advanced solid tumors. Cancer stemness pathways have been implicated in adenoid cystic carcinoma (ACC). An RP2D expansion cohort was opened for patients with ACC. Methods: Pts with metastatic, unresectable ACC for whom systemic therapy was indicated were enrolled. Amcasertib was administered orally, once or twice daily, in continuous 28-day cycles at a starting dose of 110 mg to 300 mg total daily. Adverse events were categorized according to CTCAE v4.03 and tumor imaging was evaluated per RECIST 1.1 guidelines. Results: 14 pts with ACC were enrolled. Prior treatments included surgery and radiation in all pts (100%), while 57% (n = 8) had received prior systemic therapy (average 2 prior lines, range 1 to 4). Treatment with amcasertib was well tolerated, with grade 3 diarrhea reported in 1 patient and no related grade 4 AEs. The disease control rate (DCR, proportion with stable disease at 8-weeks, partial response, or complete response per RECIST) was 86% (n = 12) with prolonged disease control (≥ 6 months) achieved in 57% (n = 8) patients. At 12 months, 79% of pts were alive. Median overall survival (mOS) was 28.3 months. Conclusions: Clinical safety and encouraging signs of anti-cancer activity were observed in pts with advanced ACC who received treatment with amcasertib. Long term follow-up demonstrates prolonged duration of disease control and that a majority of pts in this cohort have survived beyond 2 years. Further clinical evaluation of amcasertib in pts with ACC is warranted. Clinical trial information: NCT01781455.