Neo-adjuvant pembrolizumab in stage IV high-grade serous ovarian cancer: the phase II Neo-Pembro trial

S. L. Aronson, B. Thijssen, M. Lopez-Yurda, S. N. Koole, P. Leest, A. León-Castillo, R. Harkes, I. M. Seignette, J. Sanders, M. Alkemade, I. Kemper, M. J. Holtkamp, I. A. M. Mandjes, A. Broeks, M. J. Lahaye, M. A. Rijlaarsdam, D. Broek, L. F. A. Wessels, H. M. Horlings, W. J. Driel and G. S. Sonke ()
Additional contact information
S. L. Aronson: The Netherlands Cancer Institute
B. Thijssen: The Netherlands Cancer Institute
M. Lopez-Yurda: The Netherlands Cancer Institute
S. N. Koole: The Netherlands Cancer Institute
P. Leest: Netherlands Cancer Institute
A. León-Castillo: The Netherlands Cancer Institute
R. Harkes: The Netherlands Cancer Institute
I. M. Seignette: The Netherlands Cancer Institute
J. Sanders: The Netherlands Cancer Institute
M. Alkemade: Netherlands Cancer Institute
I. Kemper: The Netherlands Cancer Institute
M. J. Holtkamp: The Netherlands Cancer Institute
I. A. M. Mandjes: The Netherlands Cancer Institute
A. Broeks: Netherlands Cancer Institute
M. J. Lahaye: The Netherlands Cancer Institute
M. A. Rijlaarsdam: The Netherlands Cancer Institute
D. Broek: Netherlands Cancer Institute
L. F. A. Wessels: The Netherlands Cancer Institute
H. M. Horlings: The Netherlands Cancer Institute
W. J. Driel: The Netherlands Cancer Institute
G. S. Sonke: The Netherlands Cancer Institute

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: Abstract While immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, their efficacy in high-grade serous ovarian cancer (HGSOC) remains limited. Some patients, however, achieve lasting responses, emphasizing the need to understand how tumor microenvironment and molecular characteristics influence ICI response. The phase 2 Neo-Pembro study (NCT03126812) included 33 untreated stage IV HGSOC patients, who were scheduled for 6 cycles of carboplatin-paclitaxel and interval cytoreductive surgery. Pembrolizumab (pembro) was added from cycle two and continued for one year. The primary objective was to assess intratumoral immune activation using multiplexed immunofluorescence and immune-related gene expression. Our findings show immune activation, evidenced by an increase in CD3 + , CD8 + , CD8 + /FOXP3+ ratio, TNF-α and interferon-γ signaling. Treatment was well-tolerated. We observed major pathologic responses in 9/33 patients (27%, 95%CI 14-46), with pathologic response strongly associated with immune activation and OS. At a median follow-up of 52.8 months, 8/9 major responders were alive, with 6 patients recurrence-free. In contrast, 4/24 minor responders survived, including one recurrence-free. ctDNA clearance was observed in all major responders and was associated with prolonged PFS and OS. PD-L1 expression and homologous recombination deficiency were predictive of major response and may serve as biomarkers, warranting further exploration. These results suggest major responders may benefit from neo-adjuvant pembro.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-58440-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58440-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-58440-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().