Phase I study of the Syk inhibitor sovleplenib in relapsed or refractory mature B-cell tumors
Year: 2024
Type: article
Study design: Clinical Trial
Abstract: Sovleplenib (HMPL-523) is a selective spleen tyrosine kinase (Syk) inhibitor with anti-tumor activity in preclinical models of B-cell malignancy. We conducted a dose-escalation and dose-expansion phase I study of sovleplenib in patients with relapsed/ refractory mature B-cell tumors. Dose escalation followed a 3+3 design; patients received oral sovleplenib (200-800 mg once daily [q.d.] or 200 mg twice daily [b.i.d.], 28-day cycles). During dose expansion, patients were enrolled into four cohorts per lymphoma classification and treated at the recommended phase II dose (RP2D) (clinicaltrials gov. Identifier: NCT02857998). Overall, 134 Chinese patients were enrolled (dose escalation, N=27; dose expansion, N=107). Five patients experienced dose-limiting toxicities: one each of amylase increased (200 mg q.d.), febrile neutropenia (800 mg q.d.), renal failure (800 mg q.d.), hyperuricemia and blood creatine phosphokinase increased (200 mg b.i.d.) and blood bilirubin increased and pneumonia (200 mg b.i.d.). RP2D was determined as 600 mg (>65 kg) or 400 mg (≤65 kg) q.d.. The primary efficacy end point of independent review committee-assessed objective response rate in indolent B-cell lymphoma was 50.8% (95% confidence interval: 37.5- 64.1) in 59 evaluable patients at RP2D (follicular lymphoma: 60.5%, marginal zone lymphoma: 28.6%, lymphoplasmacytic lymphoma/Waldenström macroglobulinemia, 0%). The most common (≥10% patients) grade ≥3 treatment-related adverse events in the dose-expansion phase were decreased neutrophil count (29.9%), pneumonia (12.1%) and decreased white blood cell count (11.2%). Pharmacokinetic exposures increased dose-proportionally with ascending dose levels from 200-800 mg, without observed saturation. Sovleplenib showed anti-tumor activity in relapsed/refractory B-cell lymphoma with acceptable safety. Further studies are warranted.
Source: Haematologica
Authors: Yuqin Song, Junning Cao, Qingyuan Zhang, Caixia Li, Lugui Qiu, Junyuan Qi, Huilai Zhang, Wenyu Li, Lihong Liu, Hongmei Jing, Keshu Zhou, Weijing Zhang, Liling Zhang, Daqi Li, Liqun Zou, Haiyan Yang, Wenbin Qian, Hui Zhou, Jianda Hu, Hongyan Yin, Sisi Fu, Songhua Fan, Qian Xu, Jian Wang, Xiaoyun Jia, Guangxiu Dai, Weiguo Su, Jun Zhu
Institutions: Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Harbin Medical University, First Affiliated Hospital of Soochow University, Chinese Academy of Medical Sciences & Peking Union Medical College, Institute of Hematology & Blood Diseases Hospital, Tianjin Medical University Cancer Institute and Hospital, Guangdong Provincial People's Hospital, Fourth Hospital of Hebei Medical University, Peking University Third Hospital, Henan Cancer Hospital, Capital Medical University, Beijing Shijitan Hospital, Wuhan Union Hospital, Huazhong University of Science and Technology, Jinan Central Hospital, Shandong First Medical University, West China Hospital of Sichuan University, Zhejiang Cancer Hospital, First Affiliated Hospital Zhejiang University, Zhejiang University, Hunan Cancer Hospital, Union Hospital, HUTCHMED (China) Limited (China)
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,157
OpenAlex ID: W4390984425