Background: TGR-1202 is a novel, next generation PI3Kδ inhibitor which exhibits a differentiated safety profile from other PI3Kδ inhibitors, both approved and in development, and has demonstrated activity in patients (pts) with advanced heme malignancies (ASH 2014). Herein we present updated safety and efficacy results from a Ph I study of TGR-1202 in pts with rel/ref CLL and lymphoma.

Methods: TGR-1202 is administered orally once-daily (QD) following a 3+3 dose escalation design. Eligible pts have rel/ref non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), or other B-cell malignancy and an ECOG PS ≤ 2. Endpoints include safety, PK/PD, and efficacy.

Results: As of August 2015, 75 pts are evaluable for safety including pts with CLL, FL, Hodgkin's (HL), DLBCL, MCL, and MZL. Patients had a median age of 65 yo (range: 22-85), 67% male, ECOG 0/1/2: 26/47/2, median prior Tx: 3 (range: 1-14), and 49% refractory to prior Tx. No Gr≥3 AEs were observed in ≥10% of pts. AEs (all grades, all causality) in >20% of pts were limited to nausea (44%, Gr3/4 0%), diarrhea (36%, Gr3/4 1%), and fatigue (31%, Gr3/4 3%). Notably, general tolerability and the incidence of hepatotoxicity and colitis appear significantly less than that reported with other agents in this class. Expansion cohorts are open at 800 mg, 1000 mg, and 1200 mg QD. Of 16 evaluable CLL pts, 15 (94%) achieved a nodal PR (median nodal ↓ of 76%), of which 10 (63%) achieved a PR per Hallek 2008 criteria. Among the 32 evaluable NHL patients, 10 achieved an objective response, including 3/11 evaluable patients with DLBCL, while responses have been limited in pts with MCL (1/5) and HL (1/9). Of the 16 evaluable indolent NHL (FL & MZL) pts, 14 (88%) have achieved reductions in tumor burden with 6 pts on study for over 12 cycles (and durations upwards of 29+ cycles), with 5/12 FL and 1/4 MZL pts achieving an objective response to date. Notably, a strong exposure-response relationship has been observed. Of the 24 patients starting TGR-1202 at 800 mg or 1200 mg of the micronized formulation, 19 (79%) remain on therapy, with 9/18 (50%) evaluable pts (6 too early to evaluate) achieving an objective response to date (range on study 3 - 49+ weeks).

Conclusions: TGR-1202 is well tolerated in pts with rel/ref heme malignancies with a distinct safety and tolerability profile from other PI3K-delta inhibitors (with 43% of pts on study 6+ Cyc) and promising activity in CLL and NHL. Enrollment continues in expansion cohorts and registration directed Phase 3 studies are planned.


Flinn:Celgene Corporation: Research Funding. Fenske:Millennium/Takeda: Research Funding; Celgene: Honoraria; Seattle Genetics: Honoraria; Pharmacyclics: Honoraria. Deng:TG Therapeutics, Inc.: Honoraria, Research Funding; Seattle Genetics: Research Funding. Kuhn:TG Therapeutics, Inc.: Consultancy; Otsuka American Pharmaceutical: Consultancy; Azaya Therapeutics: Consultancy. Miskin:TG Therapeutics, Inc.: Employment, Equity Ownership. Sportelli:TG Therapeutics, Inc.: Employment, Equity Ownership. Vakkalanka:Rhizen Pharmaceuticals SA: Employment, Equity Ownership.

Author notes


Asterisk with author names denotes non-ASH members.