On 19 June 2018, a study was published in 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.
- 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)
- 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.
Chen C. et al. A phase 2 study of ofatumumab (Arzerra) in combination with pan-AKT inhibitor (afuresertib) in previously treated patients with chronic lymphocytic leukemia (CLL). Leukemia & Lymphoma. 2018 Jun 19:1-9. doi: 10.1080/10428194.2018.1468892. [Epub ahead of print]