Efficacy and Safety Results With Rilzabrutinib, an Oral Bruton Tyrosine Kinase Inhibitor, in Patients With Immune Thrombocytopenia: Phase 2 Part B Study

Abstract

Current treatments for persistent or chronic immune thrombocytopenia (ITP) are limited by inadequate response, toxicity, and impaired quality of life. The Bruton tyrosine kinase inhibitor rilzabrutinib was evaluated to further characterize safety and durability of platelet response. LUNA2 Part B is a multicenter, phase 1/2 study in adults with ITP (≥ 3 months duration, platelet count < 30 × 10⁹/L) who failed ≥ 1 ITP therapy (NCT03395210, EudraCT 2017-004012-19). Oral rilzabrutinib 400 mg bid was given over 24 weeks, with optional long-term extension (LTE). Primary endpoints were safety and platelet counts ≥ 50 × 10⁹/L on ≥ 8 of the last 12 weeks of main treatment without rescue medication. From 22 March2018 to 31 January2023, 26 patients were enrolled. Patients had baseline median platelet count 13 × 10⁹/L, ITP duration 10.3 years, and six prior ITP therapies (46% splenectomized). Nine (35%) patients achieved the primary endpoint. Platelet counts ≥ 50 × 10⁹/L or ≥ 30 × 10⁹/L and doubling from baseline without rescue therapy were sustained for a mean 9.3 weeks. 11 (42%) LTE-eligible patients were ongoing with median LTE platelet > 80 × 10⁹/L. Three (12%) patients received rescue medication during main treatment, none in LTE. Clinically meaningful improvements were observed in fatigue and women's health. With a median treatment duration of 167 days (main treatment), 16 (62%) patients had ≥ 1 treatment-related adverse event (AE), mainly grade 1, including diarrhea (35%), headache (23%), and nausea (15%). There was no treatment-related grade ≥ 2 bleeding/thrombotic events/infections, serious AE, or death. Rilzabrutinib continues to demonstrate durable platelet responses with favorable safety profile in previously treated ITP patients. Trial Registration: NCT03395210, EudraCT 2017-004012-19.

Keywords: adults; immune thrombocytopenia; platelets; quality of life; response.

FIGURE 1

Efficacy outcomes all patients including median platelet counts (interquartile range [IQR]) from trial entry for all patients in the main treatment period (A) and by response (responder^a n = 9 and non‐responder n = 17) in the main treatment period (B), swimmer's plot^b for duration of response during the main treatment period (C), and median platelet counts (IQR) for long‐term extension (LTE) patients (n = 11) during the main and LTE treatment periods (D). ^aResponder was defined as patients who met the primary endpoint. ^bThe swimmer's plot by patient per lane shows the duration of treatment with rilzabrutinib with or without concomitant corticosteroids (CS) and/or thrombopoietin receptor agonist (TPO‐RA) given at baseline, and platelet counts of < 30 × 10⁹/L (gray shading), ≥ 50 × 10⁹/L (blue shading) and ≥ 30 × 10⁹/L–< 50 × 10⁹/L (green shading). The red triangle represents prior splenectomy next to the number of prior ITP therapies (blue numbers) reported on the left side of each lane. The black triangle represents initiation of rescue medication and its duration with a black line. The blue arrow on the right of each lane signifies ongoing treatment after the 24‐week main treatment period.