Safety, pharmacokinetics, and preliminary efficacy of the PARP inhibitor talazoparib in Japanese patients with advanced solid tumors: phase 1 study.
Adult
Aged
Antineoplastic Agents
/ administration & dosage
Asian People
Dose-Response Relationship, Drug
Humans
Japan
Maximum Tolerated Dose
Middle Aged
Neoplasm Grading
Neoplasm Metastasis
Neoplasms
/ drug therapy
Phthalazines
/ administration & dosage
Poly(ADP-ribose) Polymerase Inhibitors
/ administration & dosage
PARP inhibitor
Pharmacokinetics
Phase 1
Safety
Talazoparib
Journal
Investigational new drugs
ISSN: 1573-0646
Titre abrégé: Invest New Drugs
Pays: United States
ID NLM: 8309330
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
received:
30
01
2021
accepted:
21
04
2021
pubmed:
24
6
2021
medline:
17
2
2022
entrez:
23
6
2021
Statut:
ppublish
Résumé
Talazoparib is a poly(ADP-ribose) polymerase enzyme inhibitor. This open-label, non-randomized, phase 1 study of talazoparib investigated the safety, pharmacokinetics, and preliminary antitumor activity in Japanese patients with locally advanced or metastatic solid tumors, regardless of mutations in DNA damage repair-related genes, who are resistant to/ineligible for standard therapies. Patients received talazoparib dosed orally at 0.75 or 1 mg once daily using a modified 3 + 3 dose-escalation scheme. Primary endpoint was dose-limiting toxicities during the first cycle of talazoparib. Nine patients (median age 62.0 years) were included: 3 and 6 patients at the 0.75 and 1.0 mg once-daily dose levels, respectively. No dose-limiting toxicities were reported. The most commonly reported treatment-emergent adverse events (≥2 patients) were anemia, stomatitis, maculopapular rash, platelet count decreased, neutrophil count decreased, and alanine aminotransferase increased. Three patients had grade ≥ 3 treatment-emergent adverse events (anemia, brain metastases [1 patient each], and neutrophil and white blood cell count decreased [same patient]). Two patients temporarily discontinued treatment due to a treatment-emergent adverse event, and 1 patient required a dose reduction for neutrophil count decreased (all at 1 mg once daily). Talazoparib exposure (C Single-agent talazoparib was well tolerated and had preliminary antitumor activity in Japanese patients with advanced solid tumors. ClinicalTrials.gov identifier: NCT03343054 (November 17, 2017).
Sections du résumé
BACKGROUND
Talazoparib is a poly(ADP-ribose) polymerase enzyme inhibitor. This open-label, non-randomized, phase 1 study of talazoparib investigated the safety, pharmacokinetics, and preliminary antitumor activity in Japanese patients with locally advanced or metastatic solid tumors, regardless of mutations in DNA damage repair-related genes, who are resistant to/ineligible for standard therapies.
METHODS
Patients received talazoparib dosed orally at 0.75 or 1 mg once daily using a modified 3 + 3 dose-escalation scheme. Primary endpoint was dose-limiting toxicities during the first cycle of talazoparib.
RESULTS
Nine patients (median age 62.0 years) were included: 3 and 6 patients at the 0.75 and 1.0 mg once-daily dose levels, respectively. No dose-limiting toxicities were reported. The most commonly reported treatment-emergent adverse events (≥2 patients) were anemia, stomatitis, maculopapular rash, platelet count decreased, neutrophil count decreased, and alanine aminotransferase increased. Three patients had grade ≥ 3 treatment-emergent adverse events (anemia, brain metastases [1 patient each], and neutrophil and white blood cell count decreased [same patient]). Two patients temporarily discontinued treatment due to a treatment-emergent adverse event, and 1 patient required a dose reduction for neutrophil count decreased (all at 1 mg once daily). Talazoparib exposure (C
CONCLUSIONS
Single-agent talazoparib was well tolerated and had preliminary antitumor activity in Japanese patients with advanced solid tumors. ClinicalTrials.gov identifier: NCT03343054 (November 17, 2017).
Identifiants
pubmed: 34160752
doi: 10.1007/s10637-021-01120-7
pii: 10.1007/s10637-021-01120-7
pmc: PMC8541992
doi:
Substances chimiques
Antineoplastic Agents
0
Phthalazines
0
Poly(ADP-ribose) Polymerase Inhibitors
0
talazoparib
9QHX048FRV
Banques de données
ClinicalTrials.gov
['NCT03343054']
Types de publication
Clinical Trial, Phase I
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1568-1576Informations de copyright
© 2021. The Author(s).
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