A Phase II Study to Assess the Safety and Efficacy of the Dual mTORC1/2 and PI3K Inhibitor Bimiralisib (PQR309) in Relapsed, Refractory Lymphoma.
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Embargo End Date
ICR Authors
Authors
Collins, GP
Eyre, TA
Schmitz-Rohmer, D
Townsend, W
Popat, R
Giulino-Roth, L
Fields, PA
Krasniqi, F
Soussain, C
Stathis, A
Andjelkovic, N
Cunningham, D
Mandic, D
Radulovic, S
Tijanic, I
Horowitz, NA
Kurtovic, S
Schorb, E
Schmidt, C
Dimitrijević, S
Dreyling, M
Eyre, TA
Schmitz-Rohmer, D
Townsend, W
Popat, R
Giulino-Roth, L
Fields, PA
Krasniqi, F
Soussain, C
Stathis, A
Andjelkovic, N
Cunningham, D
Mandic, D
Radulovic, S
Tijanic, I
Horowitz, NA
Kurtovic, S
Schorb, E
Schmidt, C
Dimitrijević, S
Dreyling, M
Document Type
Journal Article
Date
2021-11-01
Date Accepted
2021-10-07
Abstract
Bimiralisib is an orally bioavailable pan-phosphatidylinositol 3-kinase and mammalian target of rapamycin inhibitor which has shown activity against lymphoma in preclinical models. This phase I/II study evaluated the response rate to bimiralisib at 2 continuous dose levels (60 mg and 80 mg) in patients with relapsed/refractory lymphoma. Fifty patients were enrolled and started treatment. The most common histologies were diffuse large B-cell lymphoma (n = 17), follicular lymphoma (n = 9), T-cell lymphoma (n = 8), and others (mostly indolent). Patients had been treated with a median of 5 prior lines of treatment and 44% were considered refractory to their last treatment. Mean duration of treatment (and standard deviations) with 60 mg once daily (o.d.) was 1.3 ± 1.2 months, and with 80 mg o.d. 3.7 ± 3.9 months. On an intention to treat analysis, the overall response rate was 14% with 10% achieving a partial response and 4% a complete response. Thirty-six percent of patients were reported as having stable disease. No dose-limiting toxicities were observed during the phase I portion of the study. Overall, 70% of patients had a grade 3 treatment emergent adverse events (TEAE) and 34% had a grade 4 TEAE; 28% of patients discontinued treatment due to toxicity. The most frequent TEAEs grade ≥3 was hyperglycemia (24%), neutropenia (20%), thrombocytopenia (22%), and diarrhea (12%). Per protocol, hyperglycemia required treatment with oral antihyperglycemic agents in 28% and with insulin in 14%. At 60 mg or 80 mg continuous dosing, bimiralisib showed modest efficacy with significant toxicity in heavily pretreated patients with various histological subtypes of lymphoma.
Citation
HemaSphere, 2021, 5 (11), pp. e656 - ?
Source Title
Publisher
WILEY
ISSN
2572-9241
eISSN
2572-9241
Collections
Research Team
Medicine (RMH Smith Cunningham)