Ipatasertib shows promising activity against AKT1E17K-mutant tumours

Treatment with the pan-AKT inhibitor ipatasertib appears to induce response in patients with tumours harbouring AKT1^E17K mutations, according to a study.

The study included 35 patients with AKT1^E17K-mutant metastatic tumours, none of which had known KRAS, NRAS, HRAS, or BRAF mutations. Prior exposure to PI3K and mTOR inhibitors were permitted. All patients received ipatasertib 400 mg, administered orally once daily in a 28-day cycle until progression or unacceptable toxicity.

Objective response rate (ORR) was the primary endpoint. Secondary endpoints included progression-free survival (PFS), 6-month PFS, and toxicity.

Of the enrolled patients, 29 were included in the prespecified primary efficacy analysis. The most common histologies were breast (n=18) and gynaecologic (n=7). Most patients had more than three lines of prior therapy (65.5 percent).

The primary endpoint was met, with an ORR of 24.1 percent (90 percent confidence interval [CI], 11.9–40.6; p<0.001). All responses were partial responses. The median duration of response was 10.1 months (90 percent CI, 3.7–10.8).

In terms of safety, frequently reported toxicities of any grade were diarrhoea (n=25), nausea (n=13), and hyperglycaemia (n=9). The grade 3/4 toxicities that occurred were consistent with those reported for AKT inhibition. Twelve grade 3 events were deemed to be at least possibly related to treatment.