Contributions
Abstract: S777
Type: Oral Presentation
Presentation during EHA22: On Sunday, June 25, 2017 from 08:45 - 09:00
Location: Hall C
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 monotherapy in a double refractory iNHL population, which included a majority of patients (pts) with follicular lymphoma (FL).
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 of 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 other safety parameters. Pneumocystis jiroveci pneumonia (PJP) prophylaxis was mandated for all pts.
Results
129 pts with iNHL were treated on study. Of these, 83 pts with FL received duvelisib with a median duration of exposure of 6 mo. (range: 0.4 - 24). Median age was 64 years; 68% were male. Most FL pts had an ECOG performance status score at baseline of 0 (51%), followed by 1 (42%) and 2 (7%). Most FL pts (65%) had a FLIPI score at baseline ≥ 3, and most had either Stage 3 (46%) or Stage 4 (39%) disease. Median time from last anticancer therapy to first dose of duvelisib was 3.2 months. FL pts received a median of 3 prior anticancer regimens (range: 1 - 10); 65% of pts received ≥ 3 prior regimens, 17% ≥ 6 prior regimens.
Conclusion
In DYNAMO, duvelisib showed clinical activity in a double-refractory FL population (41% ORR, median DoR 9.2 mo., 80% 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. Updated clinical data will be available at the time of presentation.
Session topic: 19. Indolent Non-Hodgkin lymphoma - Clinical
Keyword(s): PI3K, Phase II, Follicular lymphoma, Clinical data
Abstract: S777
Type: Oral Presentation
Presentation during EHA22: On Sunday, June 25, 2017 from 08:45 - 09:00
Location: Hall C
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 monotherapy in a double refractory iNHL population, which included a majority of patients (pts) with follicular lymphoma (FL).
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 of 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 other safety parameters. Pneumocystis jiroveci pneumonia (PJP) prophylaxis was mandated for all pts.
Results
129 pts with iNHL were treated on study. Of these, 83 pts with FL received duvelisib with a median duration of exposure of 6 mo. (range: 0.4 - 24). Median age was 64 years; 68% were male. Most FL pts had an ECOG performance status score at baseline of 0 (51%), followed by 1 (42%) and 2 (7%). Most FL pts (65%) had a FLIPI score at baseline ≥ 3, and most had either Stage 3 (46%) or Stage 4 (39%) disease. Median time from last anticancer therapy to first dose of duvelisib was 3.2 months. FL pts received a median of 3 prior anticancer regimens (range: 1 - 10); 65% of pts received ≥ 3 prior regimens, 17% ≥ 6 prior regimens.
Conclusion
In DYNAMO, duvelisib showed clinical activity in a double-refractory FL population (41% ORR, median DoR 9.2 mo., 80% 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. Updated clinical data will be available at the time of presentation.
Session topic: 19. Indolent Non-Hodgkin lymphoma - Clinical
Keyword(s): PI3K, Phase II, Follicular lymphoma, Clinical data