Zhai John, Qin Yan, Zhu Jun, Song Yuqin, Shen Zhixiang, Du Xin, Jamois Candice, Brewster Michael, Shi Yuankai, Shi Jun
Roche Innovation Center Shanghai, Shanghai, China.
Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, China.
Br J Clin Pharmacol. 2017 Jul;83(7):1446-1456. doi: 10.1111/bcp.13232. Epub 2017 Feb 14.
The Phase Ib GERSHWIN study (NCT01680991) assessed the pharmacokinetic (PK) profile of obinutuzumab following multiple intravenous (i.v.) doses to Chinese patients with B-cell lymphomas, and compared findings with previous obinutuzumab PK studies in mainly Caucasian (non-Chinese) patients.
GERSHWIN was an open-label, single-arm intervention study. Patients aged >18 years with CD20+ relapsed/refractory chronic lymphocytic leukaemia (CLL), diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) were enrolled from four centres in China. The treatment period was 24 weeks; patients received obinutuzumab 1000 mg i.v. on Days (D)1, 8 and 15 of Cycle (C)1 (CLL patients: first infusion split over 2 days) and on D1 of C2-8 (all cycles: 21 days). PK parameters were estimated using non-compartmental analysis (NCA), and a population PK analysis was used to determine whether observed GERSHWIN PK data were in accordance with previous obinutuzumab PK studies in non-Chinese patients.
The PK analysis population included 48 patients: 28 patients completed all treatment cycles. NCA showed a similar PK profile in Chinese patients with FL, DLBCL and CLL. Steady-state concentrations of obinutuzumab appeared to be reached at the start of C2 irrespective of histology. There was no apparent relationship between body weight and systemic exposure. Most PK profiles observed in GERSHWIN lay within the 90% prediction interval of simulated profiles.
Obinutuzumab exposure was comparable in CLL, DLBCL and FL patients. NCA and population PK analysis indicate that PK characteristics of Chinese patients with B-cell lymphomas are similar to those in non-Chinese patients.
Ib期GERSHWIN研究（NCT01680991）评估了多次静脉注射奥滨尤妥珠单抗后，中国B细胞淋巴瘤患者的药代动力学（PK）特征，并将研究结果与之前主要针对高加索（非中国）患者的奥滨尤妥珠单抗PK研究进行比较。
GERSHWIN是一项开放标签、单臂干预研究。年龄大于18岁、患有CD20+复发/难治性慢性淋巴细胞白血病（CLL）、弥漫性大B细胞淋巴瘤（DLBCL）或滤泡性淋巴瘤（FL）的患者从中国的四个中心入组。治疗期为24周；患者在第1周期（C1）的第1、8和15天静脉注射1000mg奥滨尤妥珠单抗（CLL患者：首次输注分2天进行），并在第2-8周期（所有周期：21天）的第1天给药。使用非房室分析（NCA）估计PK参数，并采用群体PK分析来确定观察到的GERSHWIN PK数据是否与之前非中国患者的奥滨尤妥珠单抗PK研究一致。
PK分析人群包括48例患者：28例患者完成了所有治疗周期。NCA显示，中国FL、DLBCL和CLL患者的PK特征相似。无论组织学类型如何，奥滨尤妥珠单抗的稳态浓度似乎在第2周期开始时达到。体重与全身暴露之间无明显关系。GERSHWIN中观察到的大多数PK特征落在模拟特征的90%预测区间内。
CLL、DLBCL和FL患者的奥滨尤妥珠单抗暴露情况相当。NCA和群体PK分析表明，中国B细胞淋巴瘤患者的PK特征与非中国患者相似。
