Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2025 Apr 1;11(4):377-385.
doi: 10.1001/jamaoncol.2024.6797.

Pembrolizumab in Patients With Advanced Clear Cell Gynecological Cancer: A Phase 2 Nonrandomized Clinical Trial

Rebecca Kristeleit  1 , Michael-John Devlin  2 , Andrew Clamp  3 , Charlie Gourley  4   5 , René Roux  6 , Marcia Hall  7 , Rachel Nirsimloo  4 , Valentinos Kounnis  6 , Lesley Sage  8 , Priya Narayanan  9 , C Simon Herrington  5 , Rupali Arora  9 , Laura Farrelly  10 , Laura Hughes  10 , Nicholas Counsell  10 , Rowan E Miller  2   9
Affiliations
Clinical Trial

Pembrolizumab in Patients With Advanced Clear Cell Gynecological Cancer: A Phase 2 Nonrandomized Clinical Trial

Rebecca Kristeleit et al. JAMA Oncol. .

Abstract

Importance: Advanced clear cell gynecological cancers (CCGCs) have a poor prognosis, with response rates to second-line chemotherapy less than 8%. Preliminary clinical activity with programmed cell death 1 protein (PD-1) inhibitors reported in CCGC merits further investigation.

Objective: To assess the clinical benefit of pembrolizumab in patients with previously treated advanced CCGC.

Design, setting, and participants: The PEACOCC trial is a single-arm multicenter phase 2 trial conducted at 5 UK centers investigating the clinical benefit and safety of pembrolizumab. PD-1 inhibitor-naive patients with histologically confirmed advanced CCGC, radiological disease progression following 1 or more prior courses of chemotherapy, and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 to 1 were included. Patients were enrolled from March 2019 to October 2021, with data collected until July 2024.

Interventions: Pembrolizumab, 200 mg, intravenously every 21 days up to 2 years until progression, discontinuation due to toxic effects, or patient/clinician decision. Up to 1 year of retreatment on diseases progression, if stable disease, partial response, or complete response at 2 years.

Main outcomes and measures: The primary end point was progression-free survival (PFS) rate at 12 weeks using Response Evaluation Criteria in Solid Tumors version 1.1 to detect a 12-week PFS rate of 33% or greater and exclude a PFS rate of less than 15%, with 90% power and 1-sided 5% significance level. Secondary end points included objective response rate, duration of response, PFS, overall survival, safety, and quality of life.

Results: A total of 48 patients were eligible. The median (range) age was 58.5 (32-77) years, and 26 (54%) had an ECOG PS score of 0 and 22 (46%) had an ECOG PS score of 1; 41 (85%) had ovarian, 6 (13%) had endometrial, and 1 (2%) had cervical advanced CCGC. The median (range) courses prior therapy was 3 (1-6); 19 patients (40%) received prior anti-angiogenic therapy, and 19 (40%) had a platinum-free interval of more than 12 months. Grade 3 treatment-related adverse events were observed in 9 patients (19%), and no patients had grade 4 or 5 adverse events. A total of 45 of 46 patients (98%) had mismatch repair-proficient tumors. The 12-week PFS rate was 42% (95% CI, 28-57), and the best objective response rate was 25% (95% CI, 14-40), with 12 partial responses. After a median follow-up of 46.9 months (95% CI, 43.4-55.0), the median PFS was 2.7 months (95% CI, 1.3-5.4), and the median overall survival was 14.8 months (95% CI, 6.7-28.2).

Conclusions and relevance: The PEACOCC trial showed clinical benefit with pembrolizumab in patients with previously treated advanced CCGC, of whom all except 1 had MMR-proficient disease. Clinical outcomes were durable with an overall tolerable safety profile, justifying further evaluation of pembrolizumab monotherapy for advanced CCGC in a randomized clinical trial.

Trial registration: ClinicalTrials.gov Identifier: NCT03425565.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Kristeleit reported grants from Merck Sharp & Dohme during the conduct of the study; grants from GlaxoSmithKline; personal fees from Duke St Bio, Merck AG, Tubulis, Leucid Bio, AstraZeneca, InCyte, GlaxoSmithKline, Pharma&, Eisai, Merck Sharp & Dohme, Shattuck Labs, GenMab, SeaGen, Celcuity, Immunogen, and AbbVie; and nonfinancial support from Pharma& and Epsilogen outside the submitted work. Dr Devlin reported grants from Medical Research Foundation during the conduct of the study; grants from European Society of Medical Oncology; and personal fees from Bristol Myers Squibb outside the submitted work. Dr Clamp reported grants from AstraZeneca, Eisai, Verastem, Advenchen, Merck, Mural Oncology, and Corcept Therapeutics; personal fees from GlaxoSmithKline and Immunogen; and nonfinancial support from Merck Sharp & Dohme outside the submitted work. Dr Gourley reported grants paid to his institution from Merck Sharp & Dohme during the conduct of the study; grants paid to his institution from AstraZeneca, Merck Sharp & Dohme, GlaxoSmithKline, Clovis, Verastem, Novartis, BerGen Bio, MedAnnex, Roche, and Artios; and personal fees from AstraZeneca, Merck Sharp & Dohme, GlaxoSmithKline, Clovis, Verastem, Cor2Ed, PeerVoice, Pharma&, AbbVie, and Immunogen outside the submitted work; and has a patent for PCT/US2012/040805 issued and a patent for PCT/GB2013/053202 issued. Ms Farrelly reported grants from Merck Sharp and Dohme during the conduct of the study. Ms Hughes reported grants from Merck Sharp & Dohme during the conduct of the study. Mr Counsell reported grants from Merck Sharp & Dohme during the conduct of the study. Dr Miller reported personal fees from GlaxoSmithKline, AstraZeneca, AbbVie, Pharma&, Eisai, Merck Sharp & Dohme, Clovis Oncology, and Ellipses outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. CONSORT Study Flow Diagram
aMaximum permitted protocol treatment duration (initial treatment stage).
Figure 2.
Figure 2.. Treatment Efficacy
A total of 4 eligible patients had no imaging after treatment; 3 died and 1 could not be imaged due to intercurrent illness. OS indicates overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease.
See this image and copyright information in PMC

References

    1. Hasegawa K, Nagao S, Yasuda M, et al. . Gynecologic Cancer InterGroup (GCIG) consensus review for clear cell carcinoma of the uterine corpus and cervix. Int J Gynecol Cancer. 2014;24(9)(suppl 3):S90-S95. doi:10.1097/IGC.0000000000000297 - DOI - PubMed
    1. Shu CA, Zhou Q, Jotwani AR, et al. . Ovarian clear cell carcinoma, outcomes by stage: the MSK experience. Gynecol Oncol. 2015;139(2):236-241. doi:10.1016/j.ygyno.2015.09.016 - DOI - PMC - PubMed
    1. Glasspool RM, McNeish IA. Clear cell carcinoma of ovary and uterus. Curr Oncol Rep. 2013;15(6):566-572. doi:10.1007/s11912-013-0346-0 - DOI - PubMed
    1. Nigon E, Lefeuvre-Plesse C, Martinez A, et al. . Clinical, pathological, and comprehensive molecular analysis of the uterine clear cell carcinoma: a retrospective national study from TMRG and GINECO network. J Transl Med. 2023;21(1):408. doi:10.1186/s12967-023-04264-7 - DOI - PMC - PubMed
    1. Chan JK, Teoh D, Hu JM, Shin JY, Osann K, Kapp DS. Do clear cell ovarian carcinomas have poorer prognosis compared to other epithelial cell types? a study of 1411 clear cell ovarian cancers. Gynecol Oncol. 2008;109(3):370-376. doi:10.1016/j.ygyno.2008.02.006 - DOI - PubMed

Publication types

MeSH terms

Substances

Associated data