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

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...

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Detalhes bibliográficos
Autores: Madariaga, Ainhoa|||0000-0001-7166-9762, Garg, Swati, Tchrakian, Nairi, Dhani, Neesha C., Jimenez, Waldo, Welch, Stephen, MacKay, Helen, Ethier, Josee-Lyne, Gilbert, Lucy, Li, Xuan, Rodriguez, Angela, Chan, Lucy, Bowering, Valerie, Clarke, Blaise, Zhang, Tong, King, Ian, Downs, Gregory, Stockley, Tracy, Wang, Lisa, Udagani, Smitha, Oza, Amit M.|||0000-0002-9510-8641, Lheureux, Stephanie|||0000-0003-4405-5890
Tipo de documento: artigo
Data de publicação:2023
País:España
Recursos:Universitat Autònoma de Barcelona
Repositório:Dipòsit Digital de Documents de la UAB
Idioma:inglês
OAI Identifier:oai:ddd.uab.cat:289026
Acesso em linha:https://ddd.uab.cat/record/289026
https://dx.doi.org/urn:doi:10.1038/s41467-023-37084-w
Access Level:Acceso aberto
Palavra-chave:Biomarkers
Endometrial Neoplasms
Female
Humans
Neoplasm Recurrence, Local
Descrição
Resumo: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.

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