The pan-AKT inhibitor, capivasertib, demonstrated promising single-agent activity against relapsed/refractory follicular lymphoma (FL) and a patient with marginal zone lymphoma (MZL) in the phase 2 CAPITAL study.
The safety profile was considered manageable, without the typical class adverse events of colitis or pneumonitis, and no immune-mediated events or grade 5 treatment-related events. These data were presented at the International Conference on Malignant Lymphoma 2023.
The ongoing open-label, phase 2 CAPITAL trial (ClinicalTrials.gov identifier: NCT05008055) has treated 15 patients with relapsed/refractory FL or MZL with capivasertib using a 4-day on and 3-day off schedule every 28 days. The primary endpoint is objective response rate (ORR) and secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.
At baseline, the median age was 55 years and 33.3% of patients were female. There were 53.3% of patients who were White, 40.0% who were Asian, 20.0% Hispanic or Latino, and the remaining unknown. The median number of prior lines of therapy was 3 (range, 2-5), with 40.0% of patients previously treated with a PI3K inhibitor and 6.7% had a prior autologous hematopoietic stem cell transplant. There were 54.5% of patients with FL and 0 with MZL who were refractory to their last treatment.
The overall ORR was 54%, including 8% of patients who achieved a complete response. All patients developed a treatment-related adverse event (TRAE), with 20% grade 3 or higher in severity. There were 6.7% of patients with a serious TRAE. The rates of treatment discontinuation or interruption due to an AE was 6.7% and 40.0%, respectively. One patient required a dose reduction.
The most common TRAEs of any grade were diarrhea, nausea, fatigue, vomiting, and flatulence. Diarrhea events occurred primarily on dosing days and were grade 1-2 in severity. There were no immune-mediated events or treatment-related deaths.
“Capivasertib has the potential to be an alternative therapeutic option for patients with relapsed/refractory B-cell non-Hodgkin lymphoma,” the authors concluded, “with a safety profile that does not overlap with that of currently available PI3K inhibitor in this setting.”
Disclosures: This research was supported by AstraZeneca. Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of disclosures.
Hodson D, Shouse G, Shin H-J, et al. A phase II, open-label, multicenter study of capivasertib, a potent, oral pan-AKT inhibitor, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (CAPITAL). ICML 2023. June 13-17, 2023. Abstract P421.