A phase 1b/2 study of amcasertib, a first-in-class cancer stemness kinase inhibitor in advanced head and neck cancer.

Abstract

6032 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 showed safety and signs of anti-cancer activity in patients (pts) with advanced solid tumors during dose-escalation and RP2D expansion, including pts with advanced head & neck cancer. Methods: Pts with advanced, pre-treated head & neck cancers were enrolled. Amcasertib was administered orally, once or twice daily, in continuous 28-day cycles at a starting dose of 10 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 every 8 weeks. Results: A total of 21 pts were enrolled, 15 with HNSCC and 6 with salivary or parotid gland cancers. Prior treatments included radiation in 90% (19/21), surgery in 71% (15/21) and prior systemic therapy in 90% (19/21, average 3 prior lines, range 1 to 6). Amcasertib was well tolerated with 43% of pts treated at 300 mg daily (n = 9), 33% at 150 mg BID (n = 7), 19% at 200 mg daily (n = 4), and 5% at 10 mg daily (n = 1). Grade 3 AE included diarrhea (n = 4) and nausea (n = 1). Among all patients who received an evaluation per RECIST (n = 16), the objective responses rate (ORR, proportion with partial response [PR] or complete response [CR] per RECIST) was 13% and the disease control rate (DCR, proportion with stable disease [SD] at 8 weeks, PR or CR) was 50%. At 12 months, in the intent-to-treat population (n = 21) 38% of pts were alive. Median overall survival (mOS) of 7.2 months. Conclusions: Clinical safety and encouraging signs of anti-cancer activity were observed in pts with advanced head and neck cancers who have received treatment with amcasertib. Objective response, prolonged disease control, and extended survival have been observed in this pre-treated population with a poor prognosis. Further clinical evaluation of amcasertib in patients with head and neck cancers is warranted. Clinical trial information: NCT01781455.