TG Therapeutics Inc (TGTX)

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Attend this session at the 2018 ASCO Annual Meeting
Session: Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia
Type: Poster Session
Time: Monday June 4, 8:00 AM to 11:30 AM
Location: Hall A

http://abstracts.asco.org/214/AbstView_214_223539.html

A phase 2 study to assess the safety and efficacy of umbralisib (TGR-1202) in pts with CLL who are intolerant to prior BTK or PI3Kd inhibitor therapy.

Sub-category: Chronic Lymphocytic Leukemia (CLL)

Category: Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia

Meeting:2018 ASCO Annual Meeting

Abstract No: 7530

Poster Board Number: Poster Session (Board #167)

Citation: J Clin Oncol 36, 2018 (suppl; abstr 7530)

Author(s): Anthony R. Mato, Stephen J. Schuster, Nicole Lamanna, Ian Flinn, Jacqueline Claudia Barrientos, Suman Kambhampati, Bruce D. Cheson, Paul M. Barr, John M. Pagel, James Andrew Reeves, Frederick Lansigan, Jeffrey J. Pu, Alan P. Skarbnik, Gustavo A. Fonseca, Colleen Dorsey, Eline Luning Prak, Dana Paskalis, Peter Sportelli, Hari P. Miskin, Danielle M. Brander; Memorial Sloan Kettering Cancer Center, New York, NY; Abramson Cancer Center, Philadelphia, PA; New York-Presbyterian, Columbia University Medical Center, Manhasset, NY; Sarah Cannon Research Institute, Nashville, TN; Northwell Health/CLL Research and Treatment Program, New Hyde Park, NY; Sarah Cannon Research Institute at Research Medical Center, Kansas City, MO; Georgetown University Hospital, Lombardi Comprehensive Cancer Center, Washington, DC; University of Rochester Medical Center, Rochester, NY; Swedish Cancer Institute, Seattle, WA; Florida Cancer Specialists South / Sarah Cannon Research Institute, Ft Myers, FL; Dartmouth-Hitchcock Medical Center, Lebanon, NH; Penn State Hershey Cancer Institute, Hershey, PA; City of Hope, New York, NY; Florida Cancer Specialists/Sarah Cannon Research Institute, St. Petersburg, FL; Memorial Sloan Kettering Cancer Center / CLL Program, Leukemia Service, New York, NY; Clinical Immunology Laboratory at the Hospital of the University of Pennsylvania, Philadelphia, PA; TG Therapeutics, Inc., New York, NY; Duke University School of Medicine, Durham, NC

Abstract Disclosures

Abstract:
Background: Although KI therapies are generally well-tolerated, intolerance is the most common reason for discontinuation, thus representing an unmet medical need. Umbralisib (TGR-1202), a next generation PI3Kd inhibitor, has a discontinuation rate due to adverse events (AEs) of < 10%. Methods: We report results from a Ph 2 study assessing the safety/efficacy of umbralisib in CLL pts who were intolerant (defined per protocol) to a prior KI within 12 mos. AEs must have resolved to ≤ GR 1 prior to umbralisib therapy. Umbralisib (800mg QD) administered until progression or toxicity. Primary endpoint is progression-free survival (PFS). Results: 40 pts were treated as of 2/2018 (36 BTK & 4 PI3Kd intolerant). Baseline demographics: median (med) age 69 yrs (range 52-96), med prior therapies 2 (1-7), 55% male, ECOG 0-1 (92%), del17p (20%), del11q (23%), IGHV unmutated (60%). 80% required treatment within 6 mos of prior KI discontinuation. Most AE’s leading to KI discontinuation were: arthralgia, rash (9 events each), A-fib (6), diarrhea (4), bleeding, fatigue and weight loss (3 each). AEs on umbralisib are listed in the table: GR ≥3 PI3Kd-associated AE’s were limited: AST/ALT (3%); diarrhea (7.5%); rash (3%). 4 pts discontinued umbralisib due to intolerance (rash, pneumonia, pneumonitis, pancreatitis), and 1 pt due to study noncompliance. No pt discontinued umbralisib as a result of a prior KI intolerant AE. 3 pts (7.5%) had dose reductions (headache, hematologic, and colitis) and were successfully re-challenged (colitis pt on study in PR now 12 mos). Med PFS not reached with 90% of pts progression free at a med follow up 6.5 mos (range 1–15). Conclusions: Umbralisib appears to be safe and effective in KI intolerant CLL pts. These are the first data to confirm that switching from KI to an alternate PI3Kd (umbralisib) can result in disease control (PFS) without recurrence of KI intolerance toxicities. BTK mutations and CYP polymorphisms are being assessed. Clinical trial information: NCT02742090

Umbralisib AEs (all causality) in > 15% pts (n = 40).

Adverse Events All Grades % All Grades GR 3/4 % GR 3/4
Diarrhea 17 43% 3 8%
Nausea 17 43%
Thrombocytopenia 11 28% 4 10%
Insomnia 9 23%
Neutropenia 9 23% 7 18%
Dizziness 8 20%
Fatigue 8 20%
Rash 7 18% 1 3%