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Ten patients received two cycles every three weeks before planned surgery. Pathologic response occurred in 5/10, with major response in 2/10; no complete pathologic responses were observed. Radiologic partial response was seen in 3/10, stable disease in 5/10. No severe toxicity occurred. At median 22.5 months, two non-responders recurred. Clonal T cell expansion correlated with treatment response.",{"@graph":69,"@context":126},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/neoadjuvant-immune-checkpoint-blockade-in-women-with-mismatch-repair-deficient-endometrial-cancer-a-phase-i-study/336698/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/neoadjuvant-immune-checkpoint-blockade-in-women-with-mismatch-repair-deficient-endometrial-cancer-a-phase-i-study/336698.png","ImageObject",300,407,{"name":92,"@type":93},"Theodore","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118,122],{"name":109,"@type":110,"acceptedAnswer":111},"How was pembrolizumab administered in this phase I PAM study?","Question",{"text":112,"@type":113},"Ten women with resectable mismatch repair deficient endometrial cancer received two cycles of neoadjuvant pembrolizumab (200 mg IV) every three weeks before standard-of-care surgery and indicated adjuvant therapy.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What were the main efficacy outcomes of neoadjuvant treatment?",{"text":117,"@type":113},"Pathologic response was observed in 5/10 patients, including major pathologic response in 2/10, with no complete pathologic responses. Radiologic partial response occurred in 3/10, stable disease in 5/10, and 2/10 were non-evaluable on MRI.",{"name":119,"@type":110,"acceptedAnswer":120},"Did neoadjuvant pembrolizumab cause severe toxicity?",{"text":121,"@type":113},"All patients completed treatment without severe toxicity, indicating an acceptable safety and tolerability profile in this study.",{"name":123,"@type":110,"acceptedAnswer":124},"What immune-related factor correlated with treatment response?",{"text":125,"@type":113},"Monoclonal T cell expansion from immune response analyses significantly correlated with treatment response, and tumour-draining lymph nodes showed clonal overlap with intra-tumoural T cell expansion.","https://schema.org",{"og:url":83,"og:type":128,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":130,"canonical":83},"index,follow",{"doc_id":132,"site_id":62},336698,1790033795,{"code":4,"msg":5,"data":135},{"doc_id":132,"user_id":136,"nickname":92,"user_avatar":137,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":138,"file_id":139,"file_url":140,"file_type":141,"file_size":142,"view_count":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":143,"language":144,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":145,"faqs":146,"seo_title":147,"seo_description":67,"update_tm":148,"read_time":149},7971461740886,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","Article [https://doi.org/10.1038/s41467-024-52098-8](https://doi.org/10.1038/s41467-024-52098-8)  \nNeoadjuvant immune checkpoint blockade in women with mismatch repair deficient endometrial cancer: a phase I study  \nReceived: 23 February 2024  \n\n| Accepted: 26 August 2024 |\n| --- |\n| |\n| Check for updates |\n\nA list of authors and their affiliations appears at the end of the paper  \nNeoadjuvant immune checkpoint blockade (ICB) has shown unprecedented activity in mismatch repair deficient (MMRd) colorectal cancers, but its effectiveness in MMRd endometrial cancer (EC) remains unknown. In this investigator-driven, phase I, feasibility study (NCT04262089), 10 women with MMRd EC of any grade, planned for primary surgery, received two cycles of neoadjuvant pembrolizumab (200 mg IV) every three weeks. A pathologic response (primary objective) was observed in 5/10 patients, with 2 patients showing a major pathologic response. No patient achieved a complete pathologic response. A partial radiologic response (secondary objective) was observed in 3/10 patients, 5/10 patients had stable disease and 2/10 patients were non-evaluable on magnetic resonance imaging. All patients completed treatment without severe toxicity (exploratory objective). At median duration of follow-up of 22.5 months, two non-responders experienced disease recurrence. In-depth analysis of the loco-regional and systemic immune response (predefined exploratory objective) showed that monoclonal T cell expansion significantly correlated with treatment response. Tumour-draining lymph nodes displayed clonal overlap with intra-tumoural T cell expansion. All prespecified endpoints, efficacy in terms of pathologic response as primary endpoint, radiologic response as secondary outcome and safety and tolerability as exploratory endpoint, were reached. Neoadjuvant ICB with pembrolizumab proved safe and induced pathologic, radiologic, and immunologic responses in MMRd EC, warranting further exploration of extended neoadjuvant treatment.  \nEndometrial cancer (EC) is the most common gynaecological malignancy in high-income countries, with a rising incidence and mortality1,2. 20-30% of cases demonstrate DNA mismatch repair deficiency (MMRd), due to germline defects in MMR genes MLH1, MSH2, MSH6 or PMS2 (Lynch syndrome) or somatic MLH1 loss, resulting in a higher tumour mutational burden (TMB) in the majority of MMRd EC cases. Currently, these are managed by total hysterectomy and bilateral salpingo-oophorectomy, with adjuvant (chemo)radiotherapy given depending on disease grade and stage. Despite appreciable  \nshort-and long-term morbidity of such therapy3, disease recurrence is common, particularly in high-grade tumours. The unprecedented activity of immune checkpoint blockade (ICB) in MMRd tumours in the metastatic setting has motivated its investigation in earlier disease stages. A recent study in colon cancer demonstrated ~95% major pathological responses (MPRs) after only 15 days of treatment with little toxicity, raising possibility of organ-sparing approaches4. However, despite the considerable efficacy of ICB in advanced EC5,6, its activity in localised disease remains unknown. Here, we present results  \n[e-mail:](e-mail: m.de.bruyn@umcg.nl)[ m.de.bruyn@umcg.nl](e-mail: m.de.bruyn@umcg.nl); [h.w.nijman@umcg.nl](h.w.nijman@umcg.nl)  \nof the phase I PAM trial (NCT04262089), in which patients with resectable EC received 2 cycles of neoadjuvant pembrolizumab monotherapy intravenously (i.v.) every three weeks, before surgical resection and adjuvant therapy where indicated. All patients completed treatment without severe toxicity. A partial radiologic response was observed in 3 out of 10 patients, 5 out of 10 patients had stable disease on Magnetic Resonance Imaging (MRI). A pathologic response was observed in 5 out of 10 patients, with 2 patients showing a major pathologic response.  \nResults  \nPatient characteristics  \nTwelve patients were screened for enrolment between December 2020 and ","cbCaiimszRp6Zzv5","https://ap.wps.com/l/cbCaiimszRp6Zzv5","pdf",5893058,17,"English","# Results\n## Patient characteristics","[{\"question\":\"How was pembrolizumab administered in this phase I PAM study?\",\"answer\":\"Ten women with resectable mismatch repair deficient endometrial cancer received two cycles of neoadjuvant pembrolizumab (200 mg IV) every three weeks before standard-of-care surgery and indicated adjuvant therapy.\"},{\"question\":\"What were the main efficacy outcomes of neoadjuvant treatment?\",\"answer\":\"Pathologic response was observed in 5/10 patients, including major pathologic response in 2/10, with no complete pathologic responses. Radiologic partial response occurred in 3/10, stable disease in 5/10, and 2/10 were non-evaluable on MRI.\"},{\"question\":\"Did neoadjuvant pembrolizumab cause severe toxicity?\",\"answer\":\"All patients completed treatment without severe toxicity, indicating an acceptable safety and tolerability profile in this study.\"},{\"question\":\"What immune-related factor correlated with treatment response?\",\"answer\":\"Monoclonal T cell expansion from immune response analyses significantly correlated with treatment response, and tumour-draining lymph nodes showed clonal overlap with intra-tumoural T cell expansion.\"}]","Neoadjuvant immune checkpoint blockade in women with mismatch repair deficient endometrial cancer - a phase I study | PDF",1790016246,43]