DYNAMO: THE CLINICAL ACTIVITY OF DUVELISIB IN PATIENTS WITH DOUBLE-REFRACTORY SMALL LYMPHOCYTIC LYMPHOMA IN A PHASE 2 STUDY
Author(s): ,
Pier Luigi Zinzani
Affiliations:
1. Institute of Hematology Serágnoli,University of Bologna,Bologna,Italy
,
Nina Wagner-Johnston
Affiliations:
Siteman Cancer Center,Washington University,St Louis,United States
,
Carole Miller
Affiliations:
Saint Agnes Hospital,Baltimore,United States
,
Scott Tertreault
Affiliations:
Florida Cancer Specialists -Tallahassee,Tallahassee,United States
,
Francisco Passamonti
Affiliations:
University Hospital Ospedale di Circolo,Varese,Italy
,
Scott Lunin
Affiliations:
Florida Cancer Specialist,Fort Myers,United States
,
Hagop Youssoufian
Affiliations:
Verastem Inc,Needham,United States
,
James Porter
Affiliations:
Verastem Inc,Needham,United States
,
Sergio Prados
Affiliations:
Verastem Inc,Needham,United States
Ian Flinn
Affiliations:
Tennessee Oncology,Nashville,United States
(Abstract release date: May 18, 2017) EHA Learning Center. Luigi Zinzani P. May 18, 2017; 180906
Pier Luigi Zinzani
Pier Luigi Zinzani

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Abstract
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Abstract: E1130

Type: Eposter Presentation

Background
Duvelisib is an oral, dual inhibitor of PI3K-δ,γ in development for the treatment of hematologic malignancies. DYNAMO is a Phase 2 study to evaluate the safety and efficacy of duvelisib in a double refractory iNHL population, which included 28 patients (pts) with small lymphocytic lymphoma (SLL).

Aims
The primary objective was to evaluate the antitumor activity of duvelisib monotherapy in pts whose disease is refractory to rituximab and to either chemotherapy or RIT, with an additional objective to further characterize the safety duvelisib.

Methods
DYNAMO is an open-label, single-arm, safety, and efficacy study in patients (pts) with FL, small lymphocytic lymphoma (SLL), or marginal zone lymphoma (MZL), whose disease is double refractory to rituximab (monotherapy or in combination) and to chemotherapy or radioimmunotherapy. Pts received duvelisib 25 mg BID in 28-day treatment 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. 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 with iNHL were treated on study. Of these, 28 pts with SLL received duvelisib with a median duration of exposure of 9 mo. (range 6.5 - 12). Median age was 65 years; 68% were male. Most SLL pts had an ECOG performance status score at baseline of 0 (43%), followed by 1 (54%) and 2 (4%). Most SLL pts had either Stage 3 (25%) or Stage 4 (61%) disease at baseline. Median time from last anticancer therapy to first dose of duvelisib was 3 months. SLL pts received a median of 3 prior anticancer regimens (range: 1 - 18); 43% of pts received ≥ 4 prior anticancer regimens, 29% ≥ 6 regimens.

The ORR for SLL pts was 68% (95% CI: 48, 84) per IRC assessment. All responses (19) were PRs. Four (14%) pts had a best response of SD and 3 (11%) pts had a best response of PD. 2 pts were unevaluable for response. Per Investigator assessment, the ORR was 79% (including 1 CR). Median time to IRC response was 1.9 months (range 1.4 – 5.5). 93% of pts had a reduction in nodal target lesions. Among the 19 SLL pts with a response per IRC, the median DOR was 9.9 months. The median PFS among all SLL pts was 11.3 months, while the median OS was not reached. The estimated probability of survival at 12 months was 83.9%.
Among all pts treated (n=129), AEs were mostly Gr 1-2. Most common ≥ Gr 3 AEs were transient cytopenias (neutropenia [23%], anemia [12%], and thrombocytopenia [10%]), and diarrhoea (15%). 4 SLL pts had SAEs that led to discontinuation of duvelisib: NSCLC, neuroendocrine carcinoma of the skin, pseudomembranous colitis, and pneumonia. Two SLL pts has a fatal AE, 1 pneumonia and 1 viral infection.

Conclusion
In DYNAMO, duvelisib showed clinical activity in a double-refractory SLL population (68% ORR, median DOR 9.9 mo., 93% with a reduction in target lesions). Duvelisib was generally well tolerated, with a manageable safety profile with appropriate risk mitigation. Duvelisib monotherapy appears to have a favorable benefit-risk profile in double refractory SLL. Updated clinical data will be available at the time of presentation.

Session topic: 19. Indolent Non-Hodgkin lymphoma - Clinical

Keyword(s): PI3K, Indolent Non-Hodgkin's Lymphoma, Clinical Trial, Clinical data

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