KI Intolerance Study: A Phase 2 Study to Assess the Safety and Efficacy of TGR-1202 in Patients with CLL Intolerant to Prior Bruton’s Tyrosine Kinase or PI3Kδ Inhibitor Therapy

Conference Correspondent - ASCO 2017 - Chronic Lymphocytic Leukemia

Although kinase inhibitor (KI) therapies such as ibrutinib are well-tolerated overall, intolerance is the most common reason for discontinuation of such therapies in the management of patients with chronic lymphocytic leukemia (CLL) (Mato. Blood. 2016). Moreover, KI interruptions can shorten overall survival (Barr. ASCO 2015). Therefore, this poses a problem for patients who discontinue a KI due to intolerance but have ongoing efficacy.

As data have shown that an alternate KI, TGR-1202, can successfully treat these patients (Burris. ASCO 2016), researchers conducted a phase 2 study to assess the safety and activity of TGR-1202 in patients with CLL who are KI intolerant. TGR-1202 is a next-generation, highly specific PI3Kδ inhibitor. Enrollment includes up to 55 patients who have discontinued prior therapy with a Bruton’s tyrosine kinase (BTK) or PI3Kδ inhibitor due to intolerance. Intolerance is defined as ≥1 grade 3 or ≥2 grade 2 nonhematologic toxicities, ≥1 grade 3 neutropenia with infection or fever, and/or ≥1 grade 4 hematologic toxicities leading to KI discontinuation. All toxicity must have resolved to ≤grade 1 prior to dosing with TGR-1202. Furthermore, patients must be off prior KI for at least 14 days following discontinuation without disease progression. All eligible patients are treated with TGR-1202 800 mg daily and will continue treatment until disease progression, unacceptable toxicity, or the end of the study. The study’s primary end point is progression-free survival, with secondary end points, including overall response rate, duration of response, time to treatment failure, and safety profile. All patients are evaluated for response by CT and/or MRI.

The trial began October 1, 2016, and is expected to accrue in 12 to 15 months. As of June 1, 2017, 10 study sites are currently enrolling patients with an additional 4 or 5 sites to be activated.

Dorsey C, et al. ASCO Abstract TPS7569.

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Last modified: June 9, 2017
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