CT-011 - ETHNIC SENSITIVITY ASSESSMENT OF MOSUNETUZUMAB PHARMACOKINETICS (PK) IN CHINESE PATIENTS WITH RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA (FL)

M. Liao¹, J. Li¹, J. Wilkins², B. Wang¹, S. Vadhavkar¹, K. Peng¹, Y. Zhang³, D. Li³, M. Zhou³, C. Li¹, C. li¹, D. Turner¹; ¹Genentech, ²Occams Coöperatie, ³Roche (China).

Background: Mosunetuzumab (Mosun) is a first-in-class CD20×CD3 T-cell bispecific antibody approved for the treatment of relapsed/refractory follicular lymphoma (r/r FL). This Phase I study, YO43555, aims to assess the PK, safety, tolerability, and efficacy of Mosun in Chinese patients with r/r FL. Ethnic sensitivity assessment was performed to assess the PK of Mosun in Chinese patients and bridge benefit:risk from global populations to Chinese patients with r/r FL.

Methods: Mosun IV 1/2/60/30 mg Q3W regimen was administered to patients in YO43555. Mosun PK concentrations in human serum were determined using a validated enzyme-linked immunosorbent assay. The global Mosun population pharmacokinetics (popPK) model had been built previously from 439 PK-evaluable patients outside of China from Study GO29781 (NCT02500407). PK analyses based on ethnicity were performed on the r/r FL population enrolled globally on Study GO29781 (n=90) and YO43555 (n=17). The impact of ethnicity was assessed through NCA and a popPK approach.

Results: In YO43555, observed mean Mosun concentrations from Chinese patients based on NCA were similar to the global patient population, as shown in the table. The popPK model-predicted mean of Mosun PK in Chinese patients was higher than the globally enrolled population receiving the same dosing regimen but generally fell within the 95% confidence interval. The overall exposure differences AUC0-42 and Cmax0-42 comparing Chinese and the reference global population were 28% and 27%, respectively. The difference for maximum CD20 receptor occupancy (ROmax), a safety exposure metric related to acute CRS, was 13%. Differences in AUC0-42, Cmax0-42, and ROmax between Chinese and other Asian patients from the global population were 3%, < 1%, and < 1%, respectively. Differences in AUC0-42, Cmax0-42, and ROmax between Chinese and non-Asian patients from the global population were 33%, 31%, and 15%, respectively.

Conclusion: Mosun PK in Chinese patients was overall similar to the global population. A modest increase in PK metrics for Chinese patients compared to non-Asian patients is partially attributable to differences in gender and body weight. Lower values of body weight and associated exposure differences are expected to maintain a similar benefit-risk ratio. Dose adjustment of Mosun in Chinese patients with r/r FL is not warranted.