TQB3473, a novel spleen tyrosine kinase inhibitor for primary immune thrombocytopenia: a single-arm, open-label,...

Effective treatments for relapsed/refractory immune thrombocytopenia (ITP) remain limited.

TQB3473, a novel oral spleen tyrosine kinase inhibitor, was evaluated to address this unmet need.

This phase 1 study enrolled patients aged 18 to 75 years with relapsed/refractory ITP from 6 centers in China. Patients received oral TQB3473 (400, 600, or 800 mg once daily) for 24 weeks during the dose escalation and expansion phases. The primary endpoints were safety and determination of the recommended phase 2 dose.

The overall response rate (platelet count ≥ 50 × 10⁹/L at least once within 12 weeks) was 56.8%. Response rates were 0% (400 mg), 60.7% (600 mg), and 66.7% (800 mg). The durable response rate (platelet count ≥ 50 × 10⁹/L in ≥4 of the last 6 visits within 14-24 weeks) was 25% with a 600 mg dose. Treatment-related adverse events occurred in 72.9% of patients and were mostly grade 1 to 2. The most frequent treatment-related adverse events in the 600 mg cohort were increased lactate dehydrogenase (32.1%), increased aspartate aminotransferase (28.6%), increased alanine aminotransferase (25.0%), and hypertriglyceridemia (21.4%). Hypertension (3.6%) and gastrointestinal toxicity were infrequent. No thrombotic events or deaths were reported. Based on a favorable benefit-risk profile, including a longer response duration and better tolerability, 600 mg once daily was established as the recommended phase 2 dose.

The promising efficacy and favorable safety profile of TQB3473, particularly its minimal hypertension and gastrointestinal toxicity, support 600 mg once daily as the recommended dose and underscore its potential as a new treatment option for relapsed/refractory ITP, a premise currently under evaluation in a phase 3 trial.