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Phase 1A/1B dose-escalation and -expansion study to evaluate the safety, pharmacokinetics, food effects and antitumor activity of pamiparib in advanced solid tumours

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posted on 31.03.2022, 04:46 by JD Lickliter, M Voskoboynik, L Mileshkin, Hui GanHui Gan, G Kichenadasse, K Zhang, M Zhang, Z Tang, M Millward
Background: Pamiparib, a PARP1/2 inhibitor, demonstrated antitumor activity in preclinical models. Methods: This Phase 1A/1B dose-escalation/dose-expansion study enrolled adults (≥18 years) with advanced/metastatic cancer. The dose-escalation phase evaluated the recommended Phase 2 dose (RP2D), maximum tolerated dose (MTD), and pharmacokinetics; the dose-expansion phase evaluated the antitumor activity and food effects. Results: Patients (N = 101) were enrolled in dose-escalation (n = 64) and dose-expansion (n = 37). During BID dose-escalation, dose-limiting toxicities were Grade 2 nausea (n = 1, 40 mg; n = 1, 80 mg); Grade 2 nausea and Grade 2 anorexia (n = 1, 120 mg), Grade 2 nausea, Grade 3 fatigue and Grade 3 paraesthesia (n = 1, 120 mg); MTD was 80 mg BID and RP2D was 60 mg BID. Common adverse events (AEs) were nausea (69.3%), fatigue (48.5%) and anaemia (35.6%); the most common Grade ≥3 AE was anaemia (24.8%). There was a dose-proportional increase in pamiparib exposure; no food effects on pharmacokinetics were observed. In the efficacy-evaluable population (n = 77), objective response rate (ORR) was 27.3% (95% CI, 17.7–38.6%). Median duration of response was 14.9 months (95% CI, 8.7–26.3). In the epithelial ovarian cancer (EOC)-evaluable population (n = 51), ORR was 41.2% (95% CI, 27.6–55.8%). Conclusions: Pamiparib was tolerated with manageable AEs, and antitumor activity was observed in patients with EOC.

History

Publication Date

09/03/2022

Journal

British Journal of Cancer

Volume

126

Pagination

(p. 576-585)

Publisher

Springer Nature

ISSN

0007-0920

Rights Statement

© The Authors 2021 This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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