Presentation Details
| Initial Report of Part B Phase 1/2 Efficacy and Safety Results for Bruton Tyrosine Kinase Inhibitor Rilzabrutinib in Patients with Relapsed Immune Thrombocytopenia Nichola Cooper1, A.J.Gerard Jansen2, Jiri Mayer3, Michael D Tarantino4, Remco Diab5, Brad Ward6, Ahmed Daak6, David J Kuter7. 1Hammersmith Hospital, London, United Kingdom.2Erasmus MC, University Medical Center, Rotterdam, Netherlands.3Masaryk University Hospital, Brno, Czech Republic.4The Bleeding and Clotting Disorders Institute, University of Illinois College of Medicine-Peoria, Peoria, IL, USA.5Sanofi, Rotkreuz, LU, Switzerland.6Sanofi, Cambridge, MA, USA.7Hematology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA |
Abstract
Introduction: Rilzabrutinib, a potent oral reversible inhibitor of Bruton tyrosine kinase, could potentially play a role in treating immune thrombocytopenia (ITP) due to its activities in both B cells and macrophages that would reduce production of anti-platelet autoantibodies and destruction of opsonized platelets, respectively. Preliminary data indicated that rilzabrutinib treatment in patients previously treated for ITP resulted rapid and durable platelet responses with a favorable safety profile: part A of phase 1/2 clinical study (LUNA 2, NCT03395210). Objective: To investigate rilzabrutinib effects on a more refractory ITP population. Methods: Part B of multicenter, open-label, phase 1/2 study assessed safety and effectiveness of rilzabrutinib 400 mg bid. Eligible patients were aged 18-80 years, with ≥2 baseline platelet counts <30x109/L not <7 days apart in 15 days before first dose, have past response (reached platelet count ≥50x109/L) to intravenous immunoglobulin (IVIg)/anti-D or corticosteroid (CS) that was not sustained and failed ≥1 other ITP therapy (not IVIg or CS). Consistent concomitant CS/thrombopoietin receptor agonists (TPO-RA) were allowed. Primary endpoints were safety and durable platelet response (platelet counts ≥50x109/L on ≥8 of last 12 weeks of rilzabrutinib without rescue medication). Patients with platelet counts of at least 50x109/L or 30x109/L and double from baseline ≥4 of final 8 weeks of treatment without rescue medication could continue receiving rilzabrutinib for a long-term extension (LTE) period following a 24-week course of treatment. Results: Enrolled patients (N=26) had median age (range) of 57 years (20–75), females (62%), and median baseline platelet count (range) was 13 (2–24)x109/L. Patients had median duration of ITP (range) of 10.3 years (0.7–48.2) and received prior unique median ITP therapies (range), 6 (3–19; 46% splenectomy). Seventeen patients (65%) received TPO-RA and/or concurrent non-rescue CS. Nine patients (35%; 95% CI, 17%–56%) achieved primary endpoint. By day 15 of rilzabrutinib treatment, 25% of patients had platelet counts ≥50x109/L (Figure 1A). The median time to reach a platelet count of at least 50x109/L was 15 days (range, 7–134) for 16 patients who attained this level of platelet count. Over time, median platelet counts of both responders and non-responders increased, surpassing 30x109/L platelet count threshold at day 57 and 50x109/L threshold at day 120 (Figure 1B). Mean (SD) number of weeks with platelet counts ≥50x109/L and/or ≥30x109/L and doubling from baseline was both 9.3 (10.1) weeks. During main treatment, three patients (12%) received rescue medications. Fifteen patients (58%) finished 24 weeks of rilzabrutinib and 11 (42%) entered LTE. Over the main treatment period, median treatment duration (range) was 167 days (7–169). Sixteen patients (62%) had ≥1 related treatment-emergent adverse event (rTEAE), including 35% diarrhea, 23% headache, and 15% nausea. Most rTEAEs were grade 1/2, except 1 Grade 3 rTEAE (blood creatinine phosphokinase increase) was observed. No serious rTEAEs, fatalities, or grade 2 bleeding/thrombotic rTEAEs were reported. Conclusion: Part B study results were consistent with part A despite the more refractory population. Rilzabrutinib provided quick, safe, and durable platelet responses in patients with relapsed ITP, with a favorable safety profile.
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No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.