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Background Umbralisib is an oral, once-daily inhibitor of PI3Kδ and CK1e that is highly selective for the delta isoform. The UNITY-NHL trial (NCT02793583) is a multicenter, open-label, Phase 2b study evaluating umbralisib in previously treated NHL patients. Herein, we present results from the UNITY-NHL study. Methods 208 patients with R/R marginal zone, follicular, or small lymphocytic lymphoma (MZL, FL, SLL) unresponsive to prior treatments (≥1 MZL; ≥2 FL/SLL), including ≥1 anti-CD20–based therapy, were administered umbralisib 800mg orally once-daily until disease progression, unacceptable toxicity, or study withdrawal. The primary endpoint of the study was overall response rate (ORR) as assessed by an independent review committee, according to the revised IWG criteria. Results At a median follow up of 27.8 months, MZL patients (n=69) had an ORR of 49.3% (95% CI 37.0% - 61.6%) with 15.9% achieving a complete response (CR), and a Disease Control Rate (DCR: CR+PR+SD) of 82.6%. Median time-to-response (TTR): 2.8 months (95% CI 2.7 - 2.9). No patient who achieved CR has progressed to date. At a median follow up of 27.5 months, FL patients (n=117) had an ORR of 45.3% (95% CI 36.1% - 54.8%) with 5.1% achieving a CR, and a DCR of 79.5%. Median TTR: 4.6 months (95% CI 3.0 - 5.6). At a median follow up of 29.3 months, SLL patients (n=22) had an ORR of 50.0% (95% CI 28.2 - 71.8) with 4.5% achieving a CR, and a DCR of 86.4%. Median TTR: 2.7 months (95% CI 2.4 - 2.8). At least one grade ≥3 treatment-emergent adverse event (TEAE) was reported in 53.4% of patients. TEAEs led to umbralisib discontinuation in 32 patients (15.4%). Grade ≥3 TEAEs reported in ≥10% of patients: neutropenia (11.5%) and diarrhea (10.1%). Increased ALT/AST (grade ≥3) occurred in 6.7%/7.2% of patients. Conclusions Umbralisib achieved meaningful clinical activity in a heavily pretreated iNHL population. The safety profile was manageable, with a relatively low incidence of immune-mediated toxicities and AE-related discontinuations. These results suggest umbralisib has a favorable benefit-risk profile in this patient population and have supported the Accelerated Approval of umbralisib in previously treated MZL and FL patients.

Objective: Here, we report interim results from ZUMA-5, a Phase 2 study of axi-cel, an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy, in patients with relapsed/refractory iNHL. Design: Adults with relapsed/refractory follicular lymphoma (FL) or marginal zone lymphoma (MZL) after ≥2 lines of therapy (including an anti-CD20 monoclonal antibody with an alkylating agent) were eligible. Patients were leukapheresed and received conditioning chemotherapy followed by axi-cel at 2 × 106 CAR T cells/kg. The primary endpoint was objective response rate (ORR) by central review (Cheson, et al. J Clin Oncol. 2014). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety, and blood levels of CAR T cells. Results: As of 8/20/19, 94 patients (80 FL; 14 MZL) received axi-cel (median follow-up, 11.5 months). Median age was 63 years, 51% of patients had ≥3 FLIPI, 59% had high tumor bulk, 66% progressed Conclusions: Axi-cel showed significant clinical benefit, with high response rates, and a manageable safety profile in patients with relapsed/refractory iNHL. Funding provided by Kite, a Gilead Company.