Asian race and origin have no clinically meaningful effects on polatuzumab vedotin pharmacokinetics in patients with rel
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ORIGINAL ARTICLE
Asian race and origin have no clinically meaningful effects on polatuzumab vedotin pharmacokinetics in patients with relapsed/ refractory B‑cell non‑Hodgkin lymphoma Rong Shi1 · Tong Lu1 · Grace Ku1 · Hao Ding1 · Tomohisa Saito2 · Leonid Gibiansky3 · Priya Agarwal1 · Xiaobin Li1 · Jin Yan Jin1 · Sandhya Girish1 · Dale Miles1 · Chunze Li1 · Dan Lu1 Received: 20 March 2020 / Accepted: 19 July 2020 / Published online: 8 August 2020 © The Author(s) 2020
Abstract Purpose The CD79b-targeted antibody–drug conjugate polatuzumab vedotin (pola), alone and with chemoimmunotherapy, has clinical efficacy and a tolerable safety profile in B-cell non-Hodgkin lymphoma (B-NHL). We assessed (a) whether exposure from global studies of pola is comparable to Asian patients, and (b) if the recommended pola dose is appropriate in Asian patients based on exposure. Methods The pharmacokinetics (PK) of pola in Asian and global populations was characterized for three analytes (antibodyconjugated monomethyl auristatin E (MMAE) [acMMAE], total antibody, and unconjugated MMAE) in five phase 1b/2 single-agent and combination studies in B-NHL patients (JO29138 [JAPICCTI‐142580], DCS4968g [NCT01290549], GO27834 [NCT01691898], GO29044 [NCT01992653], and GO29365 [NCT02257567]). PK data were compared between Japanese phase 1 JO29138 (JAPICCTI‐142580) and global phase 1 DCS4968g (NCT01290549) studies and between Asian and nonAsian patients in the randomized relapsed/refractory B-NHL cohorts of the phase 1b/2 study GO29365 (NCT02257567). A population PK (popPK) model was used to assess the effects of Asian race and region on acMMAE and unconjugated MMAE exposure. Results PK non-compartmental analysis (NCA) parameters for the key analyte acMMAE in the Japanese JO29138 (JAPICCTI‐142580) and global phase 1 DCS4968g (NCT01290549) studies were similar. In GO29365 (NCT02257567), the phase 1b/2 combination study, mean exposure to the analytes was generally lower in Asian patients (by ~ 9.9 to 17.5%), but not to a clinically meaningful extent. Overall, the popPK model further suggested comparable PK in Asian patients with B-NHL (race or region) versus non-Asian patients. Conclusion Race has no clinically meaningful effect on pola PK. These results (and observations from efficacy/safety exposure–response analyses) support no pola dose adjustments are warranted for Asian patients with DLBCL. Keywords Ethnic sensitivity assessment · NHL · Non-hodgkin lymphoma · PK · Polatuzumab vedotin
Introduction Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00280-020-04119-8) contains supplementary material, which is available to authorized users. * Rong Shi [email protected] * Dan Lu [email protected] 1
Genentech Inc., South San Francisco, CA, USA
2
Chugai Pharmaceutical Co., Ltd., Tokyo, Japan
3
QuantPharm LLC, North Potomac, MD, USA
The antibody–drug conjugate (ADC) polatuzumab vedotin (pola; Polivy®) was approved by the United States Food and Drug Administration in June 2019 for use
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