TGR-1202, A NOVEL ONCE DAILY PI3K-DELTA INHIBITOR, DEMONSTRATES CLINICAL ACTIVITY WITH A FAVORABLE SAFETY PROFILE, LACKING HEPATOTOXICITY, IN PATIENTS WITH CLL AND B-CELL LYMPHOMA
(Abstract release date: 05/21/15)
EHA Library. A.Burris H. 06/13/15; 103192; S432
Howard A.Burris
Contributions
Contributions
Abstract
Abstract: S432
Type: Oral Presentation
Presentation during EHA20: From 13.06.2015 11:45 to 13.06.2015 12:00
Location: Room A7
Background
TGR-1202 is a novel, next generation PI3Kδ inhibitor which lacks the hepatotoxicity associated with other PI3Kδ inhibitors and is active in patients (pts) with advanced heme malignancies (ASH 2014).
Aims
Herein we present updated safety and efficacy results from a Ph I study of TGR-1202 in pts with rel/ref CLL and B-cell lymphoma.
Methods
TGR-1202 administered orally once-daily following a 3+3 dose escalation design. Eligible pts have rel/ref B-cell non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), or other B-cell malignancy and an ECOG PS < 2. Endpoints: safety, PK/PD, and efficacy.
Results
As of Feb 2015, 58 pts evaluable for safety including CLL, FL, Hodgkin’s (HL), DLBCL, MCL, and MZL. Median age 63 yo (range: 22-85), 72% male, ECOG 0/1/2: 19/38/1, median prior Tx: 3 (range: 1-14), 48% refractory to prior Tx. Safety: The only Gr≥3 AE in ≥10% of pts was neutropenia (10%). AEs (all grades, all causality) in >20% of pts were limited to diarrhea (34%), fatigue (31%), nausea (29%), and cough (26%). All diarrhea events Gr1/2, except one Gr3 event occurring in a pt in Cyc 1, which persisted for 2 days and resolved without dose interruption. Notably, in contrast to similar agents, no drug-related hepatotoxicity or colitis has been observed to date (ave time on study 7 Cyc). 2 episodes of Gr3 fatigue at 1800 mg of a new micronized formulation met the criteria for DLT. Expansion cohorts are open at 800 mg (CLL) and 1200 mg (NHL). Efficacy: A strong exposure-response relationship has been observed. Of 14 evaluable CLL pts, 13 (93%) achieved a nodal PR (median nodal ↓ of 76%), of which 7 (50%) achieved a PR per Hallek 2008 criteria. Responses have been limited in pts with DLBCL and HL. Of the 12 evaluable FL pts, 8 (67%) remain on study progression-free (range 7 - 99+ weeks), with 3 achieving a PR, notably being the 3 pts exhibiting the highest TGR-1202 plasma concentrations.
Summary
TGR-1202 is well tolerated in pts with rel/ref heme malignancies with no reported hepatotoxicity or colitis (41% of pts on study 6+ Cyc) and promising activity in CLL and NHL. Enrollment continues in expansion cohorts.
Keyword(s): B cell lymphoma, Chronic lymphocytic leukemia, PI3 kinase, PI3K
Session topic: CLL: Novel agents
Type: Oral Presentation
Presentation during EHA20: From 13.06.2015 11:45 to 13.06.2015 12:00
Location: Room A7
Background
TGR-1202 is a novel, next generation PI3Kδ inhibitor which lacks the hepatotoxicity associated with other PI3Kδ inhibitors and is active in patients (pts) with advanced heme malignancies (ASH 2014).
Aims
Herein we present updated safety and efficacy results from a Ph I study of TGR-1202 in pts with rel/ref CLL and B-cell lymphoma.
Methods
TGR-1202 administered orally once-daily following a 3+3 dose escalation design. Eligible pts have rel/ref B-cell non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), or other B-cell malignancy and an ECOG PS < 2. Endpoints: safety, PK/PD, and efficacy.
Results
As of Feb 2015, 58 pts evaluable for safety including CLL, FL, Hodgkin’s (HL), DLBCL, MCL, and MZL. Median age 63 yo (range: 22-85), 72% male, ECOG 0/1/2: 19/38/1, median prior Tx: 3 (range: 1-14), 48% refractory to prior Tx. Safety: The only Gr≥3 AE in ≥10% of pts was neutropenia (10%). AEs (all grades, all causality) in >20% of pts were limited to diarrhea (34%), fatigue (31%), nausea (29%), and cough (26%). All diarrhea events Gr1/2, except one Gr3 event occurring in a pt in Cyc 1, which persisted for 2 days and resolved without dose interruption. Notably, in contrast to similar agents, no drug-related hepatotoxicity or colitis has been observed to date (ave time on study 7 Cyc). 2 episodes of Gr3 fatigue at 1800 mg of a new micronized formulation met the criteria for DLT. Expansion cohorts are open at 800 mg (CLL) and 1200 mg (NHL). Efficacy: A strong exposure-response relationship has been observed. Of 14 evaluable CLL pts, 13 (93%) achieved a nodal PR (median nodal ↓ of 76%), of which 7 (50%) achieved a PR per Hallek 2008 criteria. Responses have been limited in pts with DLBCL and HL. Of the 12 evaluable FL pts, 8 (67%) remain on study progression-free (range 7 - 99+ weeks), with 3 achieving a PR, notably being the 3 pts exhibiting the highest TGR-1202 plasma concentrations.
Summary
TGR-1202 is well tolerated in pts with rel/ref heme malignancies with no reported hepatotoxicity or colitis (41% of pts on study 6+ Cyc) and promising activity in CLL and NHL. Enrollment continues in expansion cohorts.
Keyword(s): B cell lymphoma, Chronic lymphocytic leukemia, PI3 kinase, PI3K
Session topic: CLL: Novel agents
Abstract: S432
Type: Oral Presentation
Presentation during EHA20: From 13.06.2015 11:45 to 13.06.2015 12:00
Location: Room A7
Background
TGR-1202 is a novel, next generation PI3Kδ inhibitor which lacks the hepatotoxicity associated with other PI3Kδ inhibitors and is active in patients (pts) with advanced heme malignancies (ASH 2014).
Aims
Herein we present updated safety and efficacy results from a Ph I study of TGR-1202 in pts with rel/ref CLL and B-cell lymphoma.
Methods
TGR-1202 administered orally once-daily following a 3+3 dose escalation design. Eligible pts have rel/ref B-cell non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), or other B-cell malignancy and an ECOG PS < 2. Endpoints: safety, PK/PD, and efficacy.
Results
As of Feb 2015, 58 pts evaluable for safety including CLL, FL, Hodgkin’s (HL), DLBCL, MCL, and MZL. Median age 63 yo (range: 22-85), 72% male, ECOG 0/1/2: 19/38/1, median prior Tx: 3 (range: 1-14), 48% refractory to prior Tx. Safety: The only Gr≥3 AE in ≥10% of pts was neutropenia (10%). AEs (all grades, all causality) in >20% of pts were limited to diarrhea (34%), fatigue (31%), nausea (29%), and cough (26%). All diarrhea events Gr1/2, except one Gr3 event occurring in a pt in Cyc 1, which persisted for 2 days and resolved without dose interruption. Notably, in contrast to similar agents, no drug-related hepatotoxicity or colitis has been observed to date (ave time on study 7 Cyc). 2 episodes of Gr3 fatigue at 1800 mg of a new micronized formulation met the criteria for DLT. Expansion cohorts are open at 800 mg (CLL) and 1200 mg (NHL). Efficacy: A strong exposure-response relationship has been observed. Of 14 evaluable CLL pts, 13 (93%) achieved a nodal PR (median nodal ↓ of 76%), of which 7 (50%) achieved a PR per Hallek 2008 criteria. Responses have been limited in pts with DLBCL and HL. Of the 12 evaluable FL pts, 8 (67%) remain on study progression-free (range 7 - 99+ weeks), with 3 achieving a PR, notably being the 3 pts exhibiting the highest TGR-1202 plasma concentrations.
Summary
TGR-1202 is well tolerated in pts with rel/ref heme malignancies with no reported hepatotoxicity or colitis (41% of pts on study 6+ Cyc) and promising activity in CLL and NHL. Enrollment continues in expansion cohorts.
Keyword(s): B cell lymphoma, Chronic lymphocytic leukemia, PI3 kinase, PI3K
Session topic: CLL: Novel agents
Type: Oral Presentation
Presentation during EHA20: From 13.06.2015 11:45 to 13.06.2015 12:00
Location: Room A7
Background
TGR-1202 is a novel, next generation PI3Kδ inhibitor which lacks the hepatotoxicity associated with other PI3Kδ inhibitors and is active in patients (pts) with advanced heme malignancies (ASH 2014).
Aims
Herein we present updated safety and efficacy results from a Ph I study of TGR-1202 in pts with rel/ref CLL and B-cell lymphoma.
Methods
TGR-1202 administered orally once-daily following a 3+3 dose escalation design. Eligible pts have rel/ref B-cell non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), or other B-cell malignancy and an ECOG PS < 2. Endpoints: safety, PK/PD, and efficacy.
Results
As of Feb 2015, 58 pts evaluable for safety including CLL, FL, Hodgkin’s (HL), DLBCL, MCL, and MZL. Median age 63 yo (range: 22-85), 72% male, ECOG 0/1/2: 19/38/1, median prior Tx: 3 (range: 1-14), 48% refractory to prior Tx. Safety: The only Gr≥3 AE in ≥10% of pts was neutropenia (10%). AEs (all grades, all causality) in >20% of pts were limited to diarrhea (34%), fatigue (31%), nausea (29%), and cough (26%). All diarrhea events Gr1/2, except one Gr3 event occurring in a pt in Cyc 1, which persisted for 2 days and resolved without dose interruption. Notably, in contrast to similar agents, no drug-related hepatotoxicity or colitis has been observed to date (ave time on study 7 Cyc). 2 episodes of Gr3 fatigue at 1800 mg of a new micronized formulation met the criteria for DLT. Expansion cohorts are open at 800 mg (CLL) and 1200 mg (NHL). Efficacy: A strong exposure-response relationship has been observed. Of 14 evaluable CLL pts, 13 (93%) achieved a nodal PR (median nodal ↓ of 76%), of which 7 (50%) achieved a PR per Hallek 2008 criteria. Responses have been limited in pts with DLBCL and HL. Of the 12 evaluable FL pts, 8 (67%) remain on study progression-free (range 7 - 99+ weeks), with 3 achieving a PR, notably being the 3 pts exhibiting the highest TGR-1202 plasma concentrations.
Summary
TGR-1202 is well tolerated in pts with rel/ref heme malignancies with no reported hepatotoxicity or colitis (41% of pts on study 6+ Cyc) and promising activity in CLL and NHL. Enrollment continues in expansion cohorts.
Keyword(s): B cell lymphoma, Chronic lymphocytic leukemia, PI3 kinase, PI3K
Session topic: CLL: Novel agents
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