-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

685 Initial Report of Part B Phase 1/2 Efficacy and Safety Results for Bruton Tyrosine Kinase Inhibitor Rilzabrutinib in Patients with Relapsed Immune Thrombocytopenia

Program: Oral and Poster Abstracts
Type: Oral
Session: 311. Disorders of Platelet Number or Function: Clinical and Epidemiological: Innovative Treatments for Immune Thrombocytopenia
Hematology Disease Topics & Pathways:
Bleeding and Clotting, Biological therapies, adult, platelet disorders, Diseases, thrombocytopenias, immune mechanism, Therapies, Immunotherapy, Biological Processes, Study Population, Human
Monday, December 11, 2023: 10:30 AM

Nichola Cooper, MD1*, A.J. Gerard Jansen, MD2, Robert Bird, MBBS3*, Jiří Mayer, MD4, Michelle Sholzberg, MDCM, MSc5, Michael D. Tarantino, MD6, Mamta Garg7*, Paula F Ypma, MD, PhD8*, Vickie McDonald, MD, PhD, FRPATH, MRCP9*, Charles Percy, MD10*, Milan Košťál11*, Isaac Goncalves, MD12*, Lachezar H. Bogdanov13*, Terry B Gernsheimer, MD14, Remco Diab15*, Mengjie Yao16*, Ahmed Abd Almalik Daak, MD, PhD, MSc, DPM/MFPM15 and David J Kuter, MD, DPhil17

1Hammersmith Hospital, London, United Kingdom
2Erasmus MC, University Medical Center, Rotterdam, Netherlands
3Princess Alexandra Hospital, Woolloongabba, Australia
4Masaryk University Hospital, Brno, CZE
5Li Ka Shing Knowledge Institute University of Toronto, St. Michael’s Hospital, Toronto, ON, Canada
6The Bleeding and Clotting Disorders Institute, University of Illinois College of Medicine-Peoria, Peoria, IL
7Leicester Royal Infirmary, Leicester, United Kingdom
8Department of Hematology, HagaZiekenhuis, Den Haag, Netherlands
9Barts Health NHS Trust, The Royal London Hospital, London, United Kingdom
10NHS Foundation Trust, University Hospitals Birmingham, Birmingham, United Kingdom
11Fourth Department of Internal Medicine and Hematology, Faculty of Medicine, University Hospital of Hradec Králové, Hradec Králové, Czech Republic
12Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Parkville, Australia
13Clinic of Hematology, University Hospital, Pleven, Bulgaria
14University of Washington and Fred Hutchinson Cancer Center, Seattle, WA
15Sanofi, Cambridge, MA
16Sanofi, Bridgewater, NJ
17Hematology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA

Introduction: Rilzabrutinib is a potent oral, reversible Bruton tyrosine kinase inhibitor that can treat hematological autoimmune diseases through multiple putative mechanisms of action: (1) inhibition of B-cell activation, (2) interruption of antibody-coated cell phagocytosis by FcϒR in spleen and liver, and (3) induce sustained anti-inflammatory effects (Langrish J Immunol 2021). Preliminary evidence showed that rilzabrutinib treatment resulted in rapid and durable platelet responses with a favorable safety profile in previously treated patients with immune thrombocytopenia (ITP) as studied in part A of a phase 1/2 clinical study (LUNA 2; Kuter N Engl J Med 2022). This abstract summarizes the results of part B that focused on the durability of response with rilzabrutinib in relapsed ITP patients.

Methods: Part B of the multicenter, open-label, phase 1/2 study evaluated the efficacy and safety of rilzabrutinib 400 mg bid in patients with relapsed ITP (NCT03395210). Adult patients aged 18-80 y were eligible with ≥2 baseline platelet counts <30x109/L no less than 7 days apart in the 15 days before the first dose. Eligible patients were required to have a past response (achievement of platelet count ≥50x109/L) to intravenous immunoglobulin (IVIg)/anti-D or corticosteroid (CS) that was not sustained and failed ≥1 other ITP therapy (that was not IVIg or CS). Stable doses of concomitant CS/thrombopoietin receptor agonists (TPO-RA) were allowed with rilzabrutinib. The primary endpoints for part B were safety and durable platelet response defined as platelet counts ≥50x109/L on ≥8 of the last 12 weeks of rilzabrutinib without rescue medication. Patients completing 24 weeks of rilzabrutinib with platelet counts ≥50x109/L or ≥30x109/L and doubling from baseline in ≥4 of the last 8 weeks of treatment without rescue medication could continue rilzabrutinib in the long-term extension (LTE) period.

Results: At baseline, 26 enrolled patients had a median age of 57 y (range, 20-75), 62% were female, and median baseline platelet count was 13x109/L (range, 2-24x109/L). Patients had a median duration of ITP of 10.3 y (range, 0.7-48.2) and had received a median of 6 prior unique ITP therapies (range, 3-19; 46% splenectomy). Seventeen patients (65%) received concomitant non-rescue CS and/or TPO-RA. Nine patients (35%; 95% CI, 17%-56%) achieved the primary endpoint of durable platelet response. Approximately 25% of patients achieved platelet counts ≥50x109/L by day 15 of rilzabrutinib treatment (Figure 1A). In 16 patients who achieved platelet counts ≥50x109/L, median time to first platelet count ≥50x109/L was 15 days (range, 7-134). Median platelet counts for all patients (responders and non-responders) increased over time, exceeding the platelet count thresholds of 30x109/L at day 57 and 50x109/L at day 120 (Figure 1B). The mean number of weeks with platelet counts ≥50x109/L and/or ≥30x109/L and doubling from baseline was both 9.3 weeks (SD, 10.1). Three patients (12%) received rescue medication in the main treatment period. Fifteen patients (58%) completed 24 weeks of rilzabrutinib and 11 (42%) entered the LTE.

Over the main treatment period, the median duration of treatment was 167 days (range, 7-169). Sixteen patients (62%) had ≥1 related treatment-emergent adverse event (AE), including 35% diarrhea, 23% headache, and 15% nausea. Most AEs were grade 1 or 2; there was 1 treatment-related AE of grade 3 blood creatinine phosphokinase increase. There was no treatment-related grade ≥2 bleeding/thrombotic events or infections, serious AEs, or deaths.

Conclusion: Part B study results were consistent with part A. Rilzabrutinib demonstrated rapid, stable, and durable platelet responses in patients with relapsed ITP, with a favorable safety profile in part B.

Disclosures: Cooper: Sanofi: Honoraria; Sobi: Honoraria; Rigel: Research Funding; Novartis: Honoraria, Research Funding; Argenyx: Honoraria; Grifols: Honoraria; Amgen: Honoraria; UCB: Honoraria. Jansen: Erasmus MC: Current Employment; Principia, Argenx, Sobi, Sanofi, CSL Behring: Research Funding; European Patent Office: Patents & Royalties: P133951EP00; Novartis, 3SBIO, Amgen, Sobi: Speakers Bureau; Novartis, Sanofi: Membership on an entity's Board of Directors or advisory committees; 3SBIO, Novartis, Amgen: Other: Travel, accommodations, expenses. Bird: Amgen: Speakers Bureau; Rigel: Research Funding; Principia (Sanofi): Research Funding. Mayer: MSD: Research Funding; Novartis: Research Funding. Sholzberg: CSL Behring: Research Funding; Pfizer: Honoraria, Research Funding; Octapharma: Honoraria, Research Funding. Tarantino: Genentech: Consultancy; Biomarin: Consultancy; Novartis: Consultancy; Octapharma: Consultancy, Other: Clinical trial investigator; Principia: Consultancy; Spark: Other: Clinical trial investigator; Takeda: Other: Clinical trial investigator, Research Funding; Amgen: Consultancy. Garg: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding, Speakers Bureau; Alnylam: Honoraria, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees; Stemline Therapeutics: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Janssen: Membership on an entity's Board of Directors or advisory committees. Ypma: Janssen: Honoraria; Janssen: Other: support for attending meetings and/or travel. McDonald: Sobi: Consultancy; Novartis: Consultancy; Amgen: Consultancy; Grifols: Research Funding; Rigel: Research Funding. Percy: Roche-Chugai: Consultancy, Honoraria, Speakers Bureau; Novo Nordisk: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau; Sobi: Consultancy, Honoraria, Speakers Bureau; LFB: Consultancy, Honoraria, Speakers Bureau; University Hospitals Birmingham NHS Foundation Trust: Current Employment. Košťál: Principia Biopharma Inc, a Sanofi Company: Consultancy. Gernsheimer: Alpine Immune Science: Consultancy. Diab: Sanofi: Current Employment. Yao: Sanofi: Current Employment. Daak: Sanofi: Current Employment, Current equity holder in publicly-traded company. Kuter: Rubius: Current equity holder in publicly-traded company; AIRx, Alexion (Syntimmune), Alnylam, Alpine, Amgen, argenx, BioCryst, Bristol Myers Squibb (BMS), Caremark, Cellularity, Cellphire, Chugai, CRICO, Daiichi Sankyo, Dianthus, Electra Therapeutics, Fuji, Hemopure, Hengrui. Immunovant, Incyte, Inmagenebio: Consultancy; AIRx, Alexion (Syntimmune), Alnylam, Alpine, Amgen, Argenx, BioCryst, Bristol Myers Squibb (BMS), Caremark, Cellularity, Cellphire, Chugai, CRICO, Daiichi Sankyo, Dianthus, Electra Therapeutics, Fuji, Hemopure, Hengrui, Immunovant, Incyte, Inmagenebio, Ke: Honoraria; UpToDate: Patents & Royalties: UpToDate Chapters; Platelet Disorder Support Association: Membership on an entity's Board of Directors or advisory committees; Kezar, Kyowa-Kirin, Merck Sharp & Dohme: Honoraria; Kezar, Kyowa-Kirin, Merck Sharp Dohme, Momenta, Novartis, Nuvig, Pfizer, Platelet Biogenesis, Platelet Disorder Support Association, Protagonist, Rigel, Sanofi (Bioveratif), Sanofi (Principia), Sanofi (Genzyme), Sobi (Dova), Takeda, UCB, Up-To-Date, Zafge: Consultancy; Alnylam, BioCryst, Novartis, Rigel, Sanofi (Principia), Takeda (Bioverativ), and UCB: Research Funding.

OffLabel Disclosure: Yes, it is off label. Rilzabrutinib is an investigational therapy being evaluated in a clinical study for the treatment of patients with immune thrombocytopenia.

Previous Abstract | Next Abstract >>
*signifies non-member of ASH