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

Lickliter, JD; Voskoboynik, M; Mileshkin, L; Gan, HK; Kichenadasse, G; Zhang, K; Zhang, M; Tang, Z; Millward, M

Author(s): Lickliter, JD; Voskoboynik, M; Mileshkin, L; Gan, HK; Kichenadasse, G; Zhang, K; Zhang, M; Tang, Z; Millward, M;
Details: Publication Year 2022-03,Volume 126,Issue #4,Page 576-585
Journal Title: British Journal of Cancer
Publication Type: Research article
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.
Publisher: Nature Portfolio
Keywords: Adult; Aged; Aged, 80 and over; Female; Fluorenes/*administration & dosage/adverse effects/pharmacokinetics; Food; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoplasms/*drug therapy; Poly(ADP-ribose) Polymerase Inhibitors/*administration & dosage/adverse; effects/pharmacokinetics; Survival Analysis; Treatment Outcome
Department(s): Medical Oncology
PubMed ID: 34795408
Publisher's Version: https://doi.org/10.1038/s41416-021-01632-2
Open Access at Publisher's Site: https://doi.org/10.1038/s41416-021-01632-2
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-01-17 07:00:18

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