On 19 June 2018, a study was publishedin Leukemia & Lymphoma on a study of the combination of ofatumumab (Arzerra) and afuresertib in patients with chronic lymphocytic leukemia (CLL) by Christine Chen, Princess Margaret Cancer Centre/Ontario Cancer Institute, Toronto, Canada, and colleagues.
Afuresertib is an oral pan-AKT inhibitor and ofatumumab is a CD20 monoclonal antibody. The combination of these two therapies was tested in a phase II, open-label study in patients with relapsed or refractory (R/R) CLL.
Study Overview
- N = 28 patients were included in the study
- 68% were male and the median age was 62.5 (range, 43–76)
- Median number lines of prior therapy was 2 (range, 1–6)
- Patients were treated with intravenous ofatumumab and oral afuresertib in a lead-in phase, treatment phase and maintenance phase
- The primary endpoint was objective response rate (ORR). Responses were evaluated using the International Workshop on CLL (iWCLL) Response Criteria 2008
- The secondary endpoints included; toxicity, duration of response (DOR), progression-free survival (PFS) and overall survival (OS)
Key Findings
- The overall response was 50%
- N = 13 patients achieved a partial response and n = 1 achieved complete response
- The median DOR was 6.4 months
- Median follow-up = 13.4 months
- Median PFS = 8.5 months (95% CI, 7.7–13.2 months)
- Median OS = 34.8 months (95% CI, 21.5–not reached months)
- The most frequent adverse events (AEs) grade ≥3 were neutropenia (n = 11), thrombocytopenia (n = 7), anemia (n = 7) and lung infection (n =4)
The authors concluded that the combination of ofatumumab and afuresertib was well tolerated in patients with R/R CLL and demonstrated moderate activity. This was seen only when the combination was administered for a limited time of 18 cycles. The responses were not durable, however, and the authors suggested further investigation of the novel combination and its treatment schedules to identify optimal use.