Phase 1A/1B dose-escalation and -expansion study to evaluate the safety, pharmacokinetics, food effects and antitumor activity of pamiparib in advanced solid tumours.
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
received:
19
07
2021
accepted:
03
11
2021
revised:
25
10
2021
pubmed:
20
11
2021
medline:
11
3
2022
entrez:
19
11
2021
Statut:
ppublish
Résumé
Pamiparib, a PARP1/2 inhibitor, demonstrated antitumor activity in preclinical models. 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. 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%). Pamiparib was tolerated with manageable AEs, and antitumor activity was observed in patients with EOC. CLINICALTRIALS. NCT02361723.
Sections du résumé
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.
Identifiants
pubmed: 34795408
doi: 10.1038/s41416-021-01632-2
pii: 10.1038/s41416-021-01632-2
pmc: PMC8854719
doi:
Substances chimiques
Fluorenes
0
Poly(ADP-ribose) Polymerase Inhibitors
0
pamiparib
8375F9S90C
Banques de données
ClinicalTrials.gov
['NCT02361723']
Types de publication
Clinical Trial, Phase I
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
576-585Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2021. The Authors.
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