DYNAMO: a PHASE 2 STUDY DEMONSTRATING THE CLINICAL ACTIVITY OF DUVELISIB IN PATIENTS WITH DOUBLE‐REFRACTORY INDOLENT NON‐HODGKIN LYMPHOMA

Introduction: Duvelisib is an oral, dual inhibitor of PI3K-δ,γ being developed to treat hematologic malignancies. Methods: DYNAMO is an open-label, single-arm, safety, and efficacy study in patients (pts) with follicular lymphoma (FL), small lymphocytic lymphoma (SLL), or marginal zone lymphoma (MZL), whose disease is double-refractory to rituximab and to chemotherapy or radioimmunotherapy. Pts received duvelisib 25 mg BID in 28-day cycles until disease progression or unacceptable toxicity. The primary endpoint is overall response rate (ORR) as assessed by an independent review committee (IRC) per revised IWG criteria, with significance tested against the null hypothesis that ORR was ≤30% per IRC. Secondary endpoints include duration of response (DoR), progression-free survival (PFS), overall survival (OS), time to response (TTR), adverse events (AEs), and changes in safety laboratory values. Pneumocystis jiroveci pneumonia (PJP) prophylaxis was mandated for all pts. Results: 129 pts received duvelisib (FL = 83; SLL = 28; MZL = 18) with a median duration of exposure of 6 mo. (range 0.4 - 24). Median age was 65 years; 68% were male. Median time from last anticancer therapy to first dose of duvelisib was 3.5 months. Pts received a median of 3 prior anticancer regimens (range 1 - 18), and 40% of pts ≥ 4 regimens. 77% had disease refractory to ≥2 anticancer regimens and 96% were refractory to their last anticancer regimen. IRC-assessed ORR was 46% (p = 0.0001) (all PRs), and Investigator-assessed ORR was 58% (2 CRs). Median TTR was 1.9 mo. (range 1.4 – 11.7). 83% of pts had reduction in nodal target lesions after treatment with duvelisib. AEs were mostly Gr 1-2. Most common ≥ Gr 3 AEs were transient cytopenias (neutropenia [23%], anemia [12%], and thrombocytopenia [10%]), and diarrhoea (15%). 17% of pts discontinued duvelisib due to an AE. Opportunistic infections occurred in <5% of pts, none fatal, and were: 1 pt with pneumocystis; 3 pts with CMV infections. Six pts had an AE with outcome of death. Conclusions: In DYNAMO, duvelisib met its primary efficacy endpoint for ORR (p-value = 0.0001 against null hypothesis that ORR ≤ 30%) in a double-refractory iNHL population, with a 46% ORR, med. DoR 9.9 mo., and 83% with reduction in target lesions. Duvelisib was generally well tolerated, with a manageable safety profile with appropriate risk mitigation. Duvelisib monotherapy has a favorable benefit-risk profile in double-refractory iNHL, and may represent an important treatment option. Mature clinical data will be available at the time of presentation. Keywords: indolent lymphoma; PI3K/AKT/mTOR; small lymphocytic lymphoma (SLL). NE = not estimable * Median follow-up 11.5 mo.