A Phase 3 Study of the Efficacy and Safety of Pexidartinib in East Asian Patients with Tenosynovial Giant Cell Tumor

一项评估佩西达替尼治疗东亚腱鞘巨细胞瘤患者疗效和安全性的3期研究

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Abstract

INTRODUCTION: The aim of this study was to assess the efficacy and safety of pexidartinib, an inhibitor of colony-stimulating factor 1 receptor, in East Asian patients with tenosynovial giant cell tumor (TGCT). METHODS: This multicenter, single-arm, phase 3 study (NCT04488822) enrolled patients with symptomatic TGCT to receive pexidartinib 400 mg twice daily. The primary efficacy endpoint was overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) per central review at week 25. Secondary endpoints included ORR by tumor volume score (TVS), change in range of motion (ROM) of the affected joint, best overall response (BOR), and treatment-emergent adverse events (TEAEs). RESULTS: A total of 40 East Asian patients with TGCT received pexidartinib. RECIST v1.1 ORR was 22.5% (95% confidence interval [CI] 10.8-38.5), with no complete responses (CRs), 9 partial responses (PRs), 21 patients with stable disease (Sd), and 1 patient with progressive disease (PD). TVS ORR was 47.5% (95% CI 31.5-63.9), with no CRs, 19 PRs, 12 patients with Sd, and none with PD. At week 25, mean (standard error [SE]) change in ROM was 23.05 (3.207), with improvement noted at week 13 (15.64 [3.312]). RECIST v1.1 BOR was 30.0% (95% CI 16.6-46.5), and TVS BOR was 47.5% (95% CI 31.5-63.9). All patients had TEAEs, and grade ≥ 3 TEAEs were reported in 16 (40.0%) patients. The most common TEAEs were hair color changes (77.5%); increases in alanine aminotransferase (60.0%), aspartate aminotransferase (57.5%), and blood lactate dehydrogenase (47.5%); and pruritus (47.5%). CONCLUSIONS: In East Asian patients with symptomatic TGCT, pexidartinib demonstrated clinical benefits, with a safety profile comparable to previous reports. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04488822.

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