KEY TAKEAWAYS
- The phase II trial aimed to evaluate the efficacy and tolerability of oral CVP in persistent and chronic ITP patients.
- The primary endpoint was the proportion of participants with a platelet response. Secondary endpoints were the proportion of pts achieving pre-specified PLT count.
- The study showed promising efficacy and safety of Cevidoplenib in persistent or chronic immune thrombocytopenia pts who had failed multiple prior therapies, warranting further clinical studies.
Immune thrombocytopenia (ITP) is an autoimmune disorder caused by platelet-targeting autoantibodies. It results in a low platelet count, which can cause bruising and potentially fatal internal bleeding.
Cevidoplenib (SKI-O-703), is a highly potent and selective spleen tyrosine kinase(SYK) inhibitor and is considered efficacious in autoantibody-driven pathologies such as ITP by inhibiting B cell and Fc receptor signaling downstream.
Researchers aimed to evaluate the efficacy and tolerability of oral CVP in persistent and chronic ITP pts who are resistant to conventional treatment.
The study included pts with persistent and chronic ITP who were unresponsive or relapsed after prior treatment. Stable doses of background medications, including corticosteroids and immunosuppressive drugs, were allowed, with fixed doses for at least 2 weeks before Day 1 and unchanged throughout the 12-week treatment period. Sixty-one participants were randomly assigned in a 2:2:1 ratio to receive 400 mg, 200 mg of CVP, and placebo twice daily.
The primary endpoint was the proportion of participants with a platelet response, defined as a platelet count ≥30,000/μL and doubling the baseline (average of 2 previous counts) without the use of rescue medication. Key secondary endpoints included the proportion of participants achieving pre-specified platelet count thresholds.
About 61 pts (23 in 400mg CVP, 26 in 200 mg CVP, and 12 in PBO, respectively), severe ITP was observed (median baseline PLT of 8,500/μ), and 68.3% had received ≥3 previous lines of therapies. On cevidoplenib, (63.6%) of patients on 400 mg and (46.2%) on 200 mg achieved an overall platelet response, compared to (33.3%) in the placebo group (P=0.151and P=0.504for 400mg and 200mg CVP, respectively, vs PBO).
Participants achieving 2 or more consecutive PLT counts ≥50,000/μL without rescue medication were 40.9% on 400 mg CVP, 19.2% on 200 mg CVP, vs. 8.3% on PBO (P=0.055 and P=0.371for 400 mg and 200 mg CVP, respectively, vs. PBO). Sustained PLT count (defined retrospectively as PLT counts ≥50,000/μL at ≥4 of the last 6 visits) was reached at 27.3% on 400 mg CVP and 19.2% on 200 mg CVP vs. 0% on PBO. The mean change from baseline in the average of the last 2 available PLT counts were 41,600/μL (46,586) on 400 mg CVP, 36,020/μL (50,270) on 200 mg CVP, and 17,500/μL (26,821) on PBO.
Platelet responses to cevidoplenib were consistent regardless of prior TRO-RAs use or baseline PLT counts <15,000/μL. Adverse events (AEs) were reported in 66.7% of participants in the combined CVP groups (32 out of 48 participants treated with cevidoplenib) and 66.7% in the placebo (PBO) group (8 out of 12 participants). The most commonly reported treatment-related AEs were ALT increase (8.3%), AST increase (6.3%), and nausea (4.2%).
The majority of AEs were grade 1 or 2. Serious AEs were reported in 4.2% of the combined CVP group and 25% in the PBO group. Treatment-related grade 3 or 4 AEs were observed in 6.3% of participants in the combined CVP group and resolved spontaneously or with medical management. No deaths were observed.
The study found that cevioplenib 400 mg twice daily exhibited promising efficacy and safety in treatment-refractory ITP patients, justifying further clinical trials to validate long-term benefits.
Jang, J. H., Grosicki, S., Cheong, J. W., Syrigou, A., Kim, S., & Hwang, H. J. (2023). CEVIDOPLENIB, A SELECTIVE INHIBITOR OF SPLEEN TYROSINE KINASE (SYK), IN PERSISTENT AND CHRONIC IMMUNE THROMBOCYTOPENIA (ITP): EFFICACY AND SAFETY IN A MULTICENTER, PLACEBO CONTROLLED PHASE 2 STUDY. Presented at EHA 2023.
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT04056195
