A Phase II Study to Assess the Safety and Efficacy of the Dual mTORC1/2 and PI3K Inhibitor Bimiralisib (PQR309) in Relapsed, Refractory Lymphoma
Year: 2021
Type: article
Study design: Clinical Trial
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.
Source: HemaSphere
Authors: Graham P. Collins, Toby A. Eyre, Debora Schmitz-Rohmer, William Townsend, Rakesh Popat, Lisa Giulino-Roth, Paul A. Fields, Fatime Krasniqi, Carole Soussain, Anastasios Stathis, Nebojsa Andjelkovic, David Cunningham, Danijela Mandic, Sinisa Radulovic, Ivan Tijanic, Netanel A. Horowitz, Sabira Kurtovic, Elisabeth Schorb, Christian Schmidt, Saša Dimitrijević, Martin Dreyling
Institutions: National Health Service, Churchill Hospital, National Institute for Health and Care Research, University of Oxford, PIQUR Therapeutics (Switzerland), University College London, Weill Cornell Medicine, Guy's Hospital, Guy's and St Thomas' NHS Foundation Trust, University of Basel, Inserm, Université Paris Sciences et Lettres, Institut Curie, Istituto Oncologico della Svizzera Italiana, University of Kragujevac, Clinical Centre of Kragujevac, Royal Marsden NHS Foundation Trust, University of Banja Luka, University clinical center of Republika Srpska, University of Nis, Klinički centar Niš, Rambam Health Care Campus, University of Sarajevo, Clinical Center University of Sarajevo, University of Freiburg, University Medical Center Freiburg, Ludwig-Maximilians-Universität München
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,480
Funder: National Cancer Institute
Award: G2768810539
OpenAlex ID: W3210294221