Preliminary Efficacy and Safety Results of TQB3473, a Novel Syk Inhibitor, in Adult Patients with Immune Thrombocytopenia (ITP)

Introduction: Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized with continuous thrombocytopenia and increased bleeding risk. A proportion of patients couldn't sustainedly benefit from current therapies and there remains an unmet need. The efficacy of Syk inhibitors for treating ITP has been recognized by the approval of fostamatinib. However, the durable response of fostamatinib is only 18%. TQB3473 is a novel, potent and highly selective oral Syk inhibitor designed to target immune-mediated B cell receptor (BCR) pathways and Fcγ receptors downstream signals. Here we report the initial phase 1 results of TQB3473 in patients with relapsed/refractory ITP enrolled in TQB3473-I-02.

Methods: TQB3473-I-02 is a dose escalation and expansion study aimed to evaluate the safety, preliminary efficacy and determine the recommended phase 2 dose (RP2D) of TQB3473. Relapsed/refractory adult ITP patients with duration of more than 6 months and who have received ≥1 prior standard care of ITP therapy with an average of 2 baseline platelet counts of <30×10⁹/L in the 2 months before baseline were eligible for the study. During 3+3 dose escalation, patients received a single oral dose of TQB3473 and then hold for 3 days observation followed by continuous dosing ranging from 400mg QD to 600mg QD and 800mg QD for 24 weeks. The primary endpoints were safety and RP2D for dose escalation and achievement of ≥1 platelet counts ≥50×10⁹/L within 12 weeks without rescue medication for dose expansion, respectively.

Results: As of May 28th, 2024, 36 pts were enrolled including 400mg QD (n=3), 600mg QD (n=27) and 800mg QD (n=6). 23 (64%) were female. At enrollment for patients initiating TQB3473 across 3 dose levels, the median age was 51 y (range, 18-75); and median duration of ITP was 6.0 y (range, 0.5-31). For 27 patients at 600mg QD, the median platelet count was 8×10⁹/L including 70% <15×10⁹/L; 67% received prior TPO and 44% received TPO-RA while 15% underwent splenectomy. Overall, 21/36 (58.3%) achieved responses (≥1 platelet counts ≥50×10⁹/L within 12 weeks without rescue medication), and the response rate was 0, 63.0% and 66.7% at 400mg QD, 600mg QD and 800mg QD, respectively. The overall durable response (platelets counts ≥50×10⁹/L for at least 4 of 6 scheduled visits) rate was 30.6%, which was 0, 33.3% and 33.3% at 400mg QD, 600mg QD and 800mg QD, respectively. Median time to first platelet counts of ≥50×10⁹/L for patients responded at 600mg QD was 25 days (3-70). In primary responders, platelet counts of ≥50×10⁹/L were maintained for 89% of visits. Subgroup analyses demonstrated that the response rate and durable response rate were 61.1% and 22.2%, and 58.3% and 25.0% for patients with prior TPO and TPO-RA treatment at 600mg QD, respectively. Treatment-related adverse events (TRAEs) were reported in 75% patients across all dose levels, mostly graded 1-2. The most common TRAEs were 42% lactate dehydrogenase increased, 33% increased aspartate aminotransferase (AST) levels, 31% increased alanine aminotransferase (ALT) levels and 25% hypertriglyceridemia. 4 patients (11%) had grade 3 TRAEs including 2 increased ALT levels, 2 increased AST levels, 1 hyperglycemia, and 1 hypertension, supporting a favorable safety profile of TQB3473. No related thrombotic events or deaths were observed.

Conclusions: TQB3473 was well tolerated in adult patients with relapsed/refractory ITP. TQB3473 600mg QD demonstrated a durable, clinically significant platelet responses across all subgroups with pretreated ITP. Continued randomized phase 3 study will further assess the durable clinical benefit of TQB3473 in adult pts with relapsed/refractory ITP.