Phase I/Ib Study of Tenalisib (RP6530), a Dual PI3K delta/gamma Inhibitor in Patients with Relapsed/Refractory T-Cell Lymphoma

• Type of Material: Article
• Authors: Auris Huen, University of Texas MD Anderson Cancer Center; Bradley M. Haverkos, University of Colorado; Jasmine Zain, City Hope Comprehensive Cancer Center; Ramchandren Radhakrishnan, University of Tennessee; Mary Lechowicz, Emory University; Sumana Devata, University of Michigan; Neil J. Korman, Case Western Reserve University; Lauren Pinter-Brown, University of California Irvine; Yasuhiro Oki, University of Texas MD Anderson Cancer Center; Prajak J. Barde, Rhizen Pharmaceut SA; Ajit Nair, Rhizen Pharmaceut SA; Kasi Viswanath Routhu, Rhizen Pharmaceut SA; Srikant Viswanadha, Rhizen Pharmaceut SA; Swaroop Vakkalanka, Rhizen Pharmaceut SA; Swaminathan P. Iyer, University of Texas MD Anderson Cancer Center
• Language: English
• Date: 2020-08-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/cancers12082293
• Title of Journal or Parent Work: Cancers
• Volume: 12
• Issue: 8
• Start Page: 1
• End Page: 14
• Grant/Funding Information: This work was supported by Rhizen Pharmaceuticals SA, La Chaux-de-Fonds, Switzerland.
• Keywords: Romidepsin; maximum tolerated dose; Science & Technology; Organization; PTCL; Duvelisib; CTCL; Oncology; Response criteria; dose limiting toxicity; PI3K-DELTA,GAMMA; United States; Disease; Life Sciences & Biomedicine; Spectrum
• Research Categories: Health Sciences, Health Care Management; Health Sciences, Toxicology; Health Sciences, Oncology

Abstract

Tenalisib (RP6530), a dual phosphoinositide 3-kinase δ/γ inhibitor was evaluated in a phase I/Ib study for maximum tolerated dose (MTD), pharmacokinetics, and efficacy in patients with relapsed/refractory peripheral and cutaneous T-Cell Lymphoma (TCL). Histologically confirmed (TCL) patients, with ≥1 prior therapy received Tenalisib orally in a 28-day cycle in doses of 200 to 800 mg twice daily (800 mg in fasting and fed state) in escalation phase (n = 19) and 800 mg twice daily (fasting) in expansion phase (n = 39). The most frequently reported treatment emergent adverse events (TEAE) and related TEAE were fatigue (45%) and transaminase elevations (33%), respectively. Most frequently reported related Grade ≥3 TEAE was transaminase elevation (21%). Two dose-limiting toxicities occurred in the 800 mg fed cohort; hence, 800 mg fasting dose was deemed MTD. Tenalisib was absorbed rapidly with a median half-life of 2.28 h. Overall response rate in 35 evaluable patients was 45.7% (3 complete response (CR); 13 partial response (PR)) and median duration of response was 4.9 months. Responding tumors showed a marked downregulation of CD30, IL-31 and IL-32α. With an acceptable safety and promising clinical activity, Tenalisib can be a potential therapeutic option for relapsed/refractory TCL. Currently, a phase I/II combination study with romidepsin is ongoing.