Abstract
Introduction: Blockade of the BAFF-R signaling pathway and depletion of BAFF-R–expressing B cells may offer clinical benefit to patients with immune thrombocytopenia (ITP). ESG206, a glycoengineered humanized anti–BAFF-R monoclonal antibody, efficiently blocks B-cell activation, proliferation, and survival, and at the same time enhances ADCC towards B-cell depletion. ESG206 has shown promising efficacy and good tolerability in relapsed/refractory (R/R) B-cell malignancies and is being investigated for ITP. This report presents preliminary safety, PK, PD, and efficacy data from the Phase 1 part of an ongoing study (NCT06853444) of ESG206 in patients with primary ITP.
Methods: This Phase 1, open-label, multicenter, dose-escalation study enrolled patients with primary ITP who were previously treated with at least a corticosteroid (CS), and had a platelet count < 30 × 109/L. Patients received ESG206 at 1, 3, 6, or 9 mg/kg intravenously every 4 weeks for up to 4 doses. Concomitant CS and/or TPO-RA were allowed if the dosage was stable at least 14 days before the first ESG206 infusion. The primary objective is safety and tolerability. Secondary endpoints include PK, PD, and efficacy outcomes, such as (complete) response rates and confirmed (complete) response rates over time, time to response, and sustained response rates. Patients will be followed until 24 weeks after the first infusion to assess response durability.
Results: Up to 1 Aug 2025, 10 patients received at least one dose of ESG206 (Median [range] age, 40 [25–63] years; 3 males [30%]). Two patients received 3 infusions, 4 received 2, and 4 received 1 (two of them discontinued early due to personal decision). Median (range) time from ITP diagnosis was 57.4 (1.8–317.6) months, and median (range) baseline platelet count was 11.5 (0–19) × 109/L. Patients were previously treated with a median (range) of 4 (1–7) prior ITP therapies, including CS (100%), TPO-RAs (40%), rituximab (20%), and other immunosuppressants. ESG206 was given as monotherapy in 7 patients; while the other 2 received CS and 1 received TPO-RA as background therapy.
By cutoff, 5 patients (50%) achieved Response (platelet count ≥50 × 109/L without rescue therapy for at least 4 weeks prior to assessment and no additional ITP treatment before confirmed response). Three patients (30%) achieved Confirmed Response (≥50 × 109/L at more than 2 assessments at least 7 days apart). Five patients (50%) achieved Complete Response (platelet count ≥ 100 × 109/L without rescue therapy). Among responders, median (range) time to response was 7 (7–21) days. During treatment, 5 patients (50%) experienced adverse events (AEs), and most of them were Grade 1-2 and transient. Treatment-related AEs included rash (n=1, Grade 3) and fever (n=1, Grade 1). No patient discontinued treatment due to AEs. Pharmacokinetic results indicated a dose-dependent increase in ESG206 plasma concentrations, with a half-life of approximately 7 days across the 1–3 mg/kg dose range. PD assessment showed significant reductions of CD20+ B cells from baseline. In the 1 mg/kg group, all 4 patients had ≥ 90% reduction at Week 5; 3 of them achieved ≥ 98% reduction by Week 9. In the 3 mg/kg group, 3 patients showed ≥ 99% reduction at Week 5.
Conclusions: These represent the first data on ESG206 in patients with primary ITP. Preliminary findings suggest that partial administration of the ESG206 treatment schedule already demonstrated rapid and encouraging efficacy with a favorable tolerability profile in heavily pretreated patients with relapsed/refractory ITP. These early interim results support further clinical exploration of ESG206 in this population.
