Phase III DUO study data of Copiktra shows effect in CLL/SLL

Verastem announced new data highlighting Phase III DUO study clinical data for Copiktra (duvelisib) in patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Of 158 patients treated with duvelisib in a post-hoc analysis of Phase III DUO study data, 78% experienced lymphocytosis. Median time to onset of lymphocytosis was one week across all patients, including patients in the high-risk subgroups. Median time to resolution of lymphocytosis was 14 weeks, with a 50% reduction from baseline at 21 weeks. Similar results were observed regardless of high-risk status. Rapid shrinkage of lymph nodes was noted, with 86% of patients achieving lymph node response. Among patients who achieved a response with duvelisib at first or second assessment, 78% and 86%, respectively, experienced lymphocytosis; median time to resolution of lymphocytosis in these patients was 12 and 18 weeks, respectively.

Prolonged lymphocytosis (for more than 12 months) occurred in 12 patients (8%). The overall response rate in patients with prolonged lymphocytosis was 83%. Of note, the median PFS was similar among patients with and without prolonged lymphocytosis; 22.1 months (95% CI, 12.9-27.6), compared to 24 months (95% CI, 20.5-NE), respectively. Overall, there were low rates of tumor lysis syndrome (1 patient; 0.6%). These results showed that duvelisib monotherapy induced rapid and transient lymphocytosis temporally associated with a reduction in lymphadenopathy in patients with relapsed or refractory CLL/SLL.

Among the 158 Copiktra-treated patients in the DUO study, the median duration of exposure was 11.6 months, versus 5.3 months for patients treated with ofatumumab. The most common cause of dose interruption was diarrhea (23%), followed by neutropenia (12%) and pneumonia or colitis (11% each). Among responders (n=118), median time to first response on Copiktra was 1.9 months and the estimated median duration of response was 11.1 months. Median time to first dose interruption was 3.9 months and median duration of dose interruption was 15 days (range 1 to 133 days). Response to Copiktra was improved or maintained in most patients evaluated for response who had at least one dose interruption for more than 1 week (84%) or more than 2 weeks (82%) followed by at least 3 weeks on Copiktra.

In a landmark analysis, median PFS was similar in patients with dose interruptions and those without dose interruptions for more than 1 week (17.8 versus 16.3 months) or more than 2 weeks (17.8 versus 16.3 months) within the first 3 months. The median time to dose reduction after a complete response or partial response was 5.6 months (n=25) and median duration was 3.4 months. Median time to onset across adverse events of special interest (AESIs) after starting Copiktra ranged from 2.2 to 4.3 months. Median time to resolution was within 4 weeks across AESIs. Proportions of patients experiencing AESIs were stable or decreased over time after 3-6 months: 0-3 months, 64%; more than 3-6 months, 63%; more than 6-9 months, 47%; more than 9-12 months, 52%, and seldom led to discontinuation of Copiktra (less or equal to 10%). These findings support the thesis that dose interruptions or dose reductions may be useful in managing TEAEs with Copiktra and that dose interruptions of beyond 1-2 weeks or more did not appear to significantly impact response to Copiktra or PFS. Data were presented at the European Hematology Association (EHA) 2019 Annual Meeting.