On October 26, AstraZeneca announced that the Phase III CAPItello-291 study of its Akt1/2/3 inhibitor capivasertib in combination with fulvestrant in breast cancer patients met the primary endpoint.
Breast cancer is the most common cancer worldwide, with approximately 70% being HR positive (expressing ER or progesterone receptor, or both) and HER2 low or negative. HR-positive breast cancer is the most common breast cancer subtype, and endocrine therapy is the first-line treatment for HR+ advanced breast cancer, and is often combined with CDK4/6 inhibitors. However, many patients with advanced breast cancer develop resistance to CDK4/6 inhibitors and existing endocrine therapies, resulting in limited treatment options.
Capivasertib is a potent oral Akt1/2/3 inhibitor independently developed by AstraZeneca. According to the results of tolerability and target inhibition in the early clinical trials, intermittent dosing was adopted, and the drug was continuously administered for 4 days and then suspended for 3 days.
The CAPItello-291 study is a global, multicenter double-blind, randomized Phase III clinical trial of 708 patients evaluating capivasertib plus fulvestrant versus placebo plus fulvestrant in the treatment of ER+ Efficacy and safety in patients with /HER2- breast cancer whose disease has relapsed or progressed during or after treatment with an aromatase inhibitor. The primary endpoint of the trial was progression-free survival (PFS) in the overall population and in the subgroup of patients with PIK3CA/AKT1/PTEN mutations, approximately 40% of whom had PIK3CA/AKT1/PTEN mutations.
The results showed a statistically and clinically meaningful improvement in PFS in patients in the capivasertib plus fulvestib cohort, both in the overall population and in subgroups with PIK3CA/AKT1/PTEN mutations. In addition, the safety profile of capivasertib in combination with fulvestrant was similar to that reported previously. Specific data will be presented at an upcoming medical meeting.
There are 26 Akt inhibitors under research globally, of which 2 are in Phase III and 14 are in Phase I/II. ipatasertib is another Phase III Akt inhibitor being developed by Pfizer and Roche. Currently, ipatasertib is conducting three Phase III clinical trials, two of which are in HR+ breast cancer and one in triple-negative breast cancer.