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

Jason D. Lickliter, Mark Voskoboynik, Linda Mileshkin, Hui K. Gan, Ganessan Kichenadasse, Kathy Zhang, Maggie Zhang, Zhiyu Tang, Michael Millward

    Research output: Contribution to journalArticlepeer-review

    Abstract

    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. ClinicalTrials.gov Identifier: NCT02361723.

    Original languageEnglish
    Pages (from-to)576-585
    Number of pages10
    JournalBritish Journal of Cancer
    Volume126
    Issue number4
    Early online date18 Nov 2021
    DOIs
    Publication statusPublished - 9 Mar 2022

    Keywords

    • phase 1A/1B
    • dose-escalation
    • pamiparib
    • Solid tumor
    • pharmacokinetics
    • antitumor activity
    • adverse events

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