LAUSR

CD20 antigen. Bendamustine (Benda) is an active chemotherapy agent in pts with lymphoma. The combination of UTX + TGR‐ 1202 is tolerable and active in pts with rel/ref hematologic malignancies and is under Phase 3 testing for pts with CLL and under Phase 2b testing for pts with DLBCL. This Phase 1 trial evaluates the safety and efficacy of UTX + TGR‐1202 + Benda in pts with advanced diffuse large B‐cell lymphoma (DLBCL) and Follicular Lymphoma (FL). Methods: Eligible pts had rel/ref DLBCL or FL with an ECOG PS ≤ 2 w/ o limit to number of prior therapies. ANC of ≥750 and Platelets ≥50,000 was permitted. Pts refractory to prior PI3Kδ, Benda, or anti‐ CD20 therapy were eligible. UTX was dosed on Days 1, 8, 15 of Cycle 1, Day 1 of Cycle 2–6, followed by Cycle 9 and 12. TGR‐1202 was started at 800 mg QD with a −1 dose reduction cohort at 600 mg if not tolerated in ≥2/6 pts. Benda was dosed at 90 mg/m on Days 1 and 2 of Cycles 1–6 only. Primary endpoints included safety and efficacy (Cheson 2007). Results: Twenty‐three pts were evaluable for safety: 15 diffuse large B‐cell (DLBCL) and 8 follicular (FL). Med age 68 yo (range 31‐81); 12 M/11 F; median prior treatment regimens = 2 (range 1–6); 12 pts (52%) were refractory to their immediate prior treatment and to prior CD20 therapy, and 7 pts had progressed post‐ transplant. ECOG PS 0/1/2 (3/18/2). Initially, 2/4 pts at 800 mg TGR‐1202 experienced AE's in Cycle 1 that led to treatment interruption (rash, neutropenia); thus, the 600 mg dose of TGR‐1202 was explored. No additional Cycle 1 treatment delays were reported at the 600‐mg dose level, which was later expanded, and the 800‐mg TGR‐1202 dose is now being evaluated with stricter eligibility criteria to require an ANC of ≥1.0, and the use of growth factor support in cycle 1 is now encouraged. The most common AE's included diarrhea (39%; G3/4 4%), decreased appetite (35%; G3/4 4%), nausea (30%; G3/4 4%), asthenia (26%; G3/4 4%) and neutropenia (22%). The only Grade 3/4 AE reported in >10% of pts was neutropenia (22%). Two pts had a TGR‐1202 dose reduction. Nineteen pts (11 DLBCL/8 FL) were evaluable for efficacy: ORR amongst all pts was 79% (15/19) with 42% (8/19) achieving a complete response (CR), of which 5 were DLBCL and 3 FL. ORR in the respective groups is as follows: