Clinical outcome and biomarker assessments of a multi-centre phase II trial assessing niraparib with or without dostarlimab in recurrent endometrial carcinoma.

Female Humans Neoplasm Recurrence, Local / drug therapy Endometrial Neoplasms / drug therapy Biomarkers

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
15 03 2023
Historique:
received: 02 08 2022
accepted: 02 03 2023
entrez: 16 3 2023
pubmed: 17 3 2023
medline: 21 3 2023
Statut: epublish

Résumé

This multi-centre, non-randomized, open-label, phase II trial (NCT03016338), assessed niraparib monotherapy (cohort 1, C1), or niraparib and dostarlimab (cohort 2, C2) in patients with recurrent serous or endometrioid endometrial carcinoma. The primary endpoint was clinical benefit rate (CBR), with ≥5/22 overall considered of interest. Secondary outcomes were safety, objective response rate (ORR), duration of response, progression free survival and overall survival. Translational research was an exploratory outcome. Potential biomarkers were evaluated in archival tissue by immunohistochemistry and next generation sequencing panel. In C1, 25 patients were enrolled, and CBR was 20% (95% CI: 9-39) with median clinical benefit duration of 5.3 months. The ORR was 4% (95% CI: 0-20). In C2, 22 patients were enrolled, and the CBR was 31.8% (95% CI: 16-53) with median clinical benefit duration of 6.8 months. The ORR was 14% (95% CI: 3-35). No new safety signals were detected. No significant association was detected between clinical benefit and IHC markers (PTEN, p53, MMR, PD-L1), or molecular profiling (PTEN, TP53, homologous recombination repair genes). In conclusion, niraparib monotherapy did not meet the efficacy threshold. Niraparib in combination with dostarlimab showed modest activity.

Identifiants

DOI: 10.1038/s41467-023-37084-w PMID: 36922497 PMC: PMC10017680
pubmed: 36922497
doi: 10.1038/s41467-023-37084-w
pii: 10.1038/s41467-023-37084-w
pmc: PMC10017680
doi:

Substances chimiques

dostarlimab 0
niraparib HMC2H89N35
Biomarkers 0

Types de publication

Multicenter Study Clinical Trial, Phase II Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1452

Informations de copyright

© 2023. The Author(s).

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Auteurs

Ainhoa Madariaga (A)

Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
University of Toronto, Toronto, ON, Canada.
Autonomous University of Barcelona, Barcelona, Spain.
Department of Medical Oncology, 12 de Octubre University Hospital, Madrid, Spain.
ORCID: 0000-0001-7166-9762

Swati Garg (S)

Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.

Nairi Tchrakian (N)

University of Toronto, Toronto, ON, Canada.
Department of Pathology and Laboratory Medicine, University Health Network, Toronto, ON, Canada.

Neesha C Dhani (NC)

Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
University of Toronto, Toronto, ON, Canada.

Waldo Jimenez (W)

Division of Gynecologic Oncology, Juravinski Cancer Centre, Hamilton, ON, Canada.

Stephen Welch (S)

Division of Medical Oncology and Hematology, London Health Sciences Center, London Regional Cancer Program, London, ON, Canada.

Helen MacKay (H)

Division of Medical Oncology and Hematology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.

Josee-Lyne Ethier (JL)

Division of Medical Oncology and Hematology, Kingston Health Sciences Cancer Centre, Kingston, ON, Canada.

Lucy Gilbert (L)

Division of Gynecologic Oncology, McGill University Health Centre, Royal Victoria Hospital, Montréal, QC, Canada.

Xuan Li (X)

Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.

Angela Rodriguez (A)

Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.

Lucy Chan (L)

Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.

Valerie Bowering (V)

Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.

Blaise Clarke (B)

University of Toronto, Toronto, ON, Canada.
Department of Pathology and Laboratory Medicine, University Health Network, Toronto, ON, Canada.

Tong Zhang (T)

Division of Clinical Laboratory Genetics, Laboratory Medicine Program, University Health Network, Toronto, ON, Canada.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.

Ian King (I)

Division of Clinical Laboratory Genetics, Laboratory Medicine Program, University Health Network, Toronto, ON, Canada.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.

Gregory Downs (G)

Division of Clinical Laboratory Genetics, Laboratory Medicine Program, University Health Network, Toronto, ON, Canada.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
ORCID: 0000-0002-5622-9010

Tracy Stockley (T)

Division of Clinical Laboratory Genetics, Laboratory Medicine Program, University Health Network, Toronto, ON, Canada.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
ORCID: 0000-0002-4476-9722

Lisa Wang (L)

University of Toronto, Toronto, ON, Canada.
Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.

Smitha Udagani (S)

Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.

Amit M Oza (AM)

Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
University of Toronto, Toronto, ON, Canada.

Stephanie Lheureux (S)

Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. stephanie.lheureux@uhn.ca.
University of Toronto, Toronto, ON, Canada. stephanie.lheureux@uhn.ca.

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Classifications MeSH

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