{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T13:19:00Z","timestamp":1787663940047,"version":"build-2736575974"},"reference-count":22,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002066","name":"GlaxoSmithKline foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Dostarlimab in combination with carboplatin\u2013paclitaxel was approved for primary advanced or recurrent endometrial cancer (pA\/rEC). The first interim analysis (IA1) of RUBY Part 1 (NCT03981796) showed no significant exposure\u2013response (ER) relationship for progression\u2010free survival or for the five most common dostarlimab\u2010related adverse events (AEs), except rash. Herein, we report the ER relationship between dostarlimab exposure and overall survival (OS) and between dostarlimab exposure and dostarlimab\u2010related AEs. Population pharmacokinetic model was based on IA1, and the predicted exposure metrics from Cycle 1 were used to perform ER analysis at the second interim analysis (IA2). AE analysis was completed for three periods: Cycles 1\u20106 (chemotherapy phase), Cycle 7 and beyond (monotherapy phase), and all cycles. Included in the OS analysis were 232 patients treated with dostarlimab + carboplatin\u2013paclitaxel. Cox regression of OS showed no significant ER relationship based on dostarlimab Cycle 1 exposure, except for rash and arthralgia. The increase in predicted probabilities for rash and arthralgia for patients with high versus low exposure was limited, ranging from 5.6% to 10.4% for rash and 4.3% to 17.7% for arthralgia (deemed not clinically relevant). These data support the risk\/benefit profile at the selected dose of dostarlimab + carboplatin\u2013paclitaxel as standard of care in patients with pA\/rEC.<\/jats:p>","DOI":"10.1002\/cpdd.70087","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T14:52:48Z","timestamp":1785941568000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exposure\u2013Response Relationship of Dostarlimab in Primary Advanced\/Recurrent Endometrial Cancer: Results From Interim Analysis 2 of Part 1 of the RUBY Trial"],"prefix":"10.1002","volume":"15","author":[{"given":"Mita","family":"Kuchimanchi","sequence":"first","affiliation":[{"name":"GSK  Waltham MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trine Lembrecht","family":"J\u00f8rgensen","sequence":"additional","affiliation":[{"name":"Department of Oncology Odense University Hospital  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Hanze","sequence":"additional","affiliation":[{"name":"qPharmetra  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Jain","sequence":"additional","affiliation":[{"name":"Fox Chase Cancer Center  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oskar","family":"Alsk\u00e4r","sequence":"additional","affiliation":[{"name":"qPharmetra  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleksandr","family":"Zub","sequence":"additional","affiliation":[{"name":"Chernihiv Medical Center of Modern Oncology Chernihiv Regional Council  Chernihiv Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark S.","family":"Shahin","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology Penn State Hershey Medical Center  Hershey PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthoula","family":"Koliadi","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology Uppsala University Hospital  Uppsala Sweden"},{"name":"Nordic Society of Gynaecological Oncology (NSGO) Clinical Trial Unit  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhavana","family":"Pothuri","sequence":"additional","affiliation":[{"name":"Departments of Obstetrics and Gynecology and Medicine Division of Gynecologic Oncology NYU Langone Health New York NY USA"},{"name":"GOG Foundation  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Krivak","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology The Western Pennsylvania Hospital  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikalai","family":"Pishchyk","sequence":"additional","affiliation":[{"name":"Grodno Regional Clinical Hospital  Grodno Belarus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yakir","family":"Segev","sequence":"additional","affiliation":[{"name":"Carmel Medical Center Technion\u2010Israel Institute of Technology  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floor J.","family":"Backes","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology Ohio State University  Columbus OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Gennigens","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology CHU of Li\u00e8ge  Li\u00e8ge Belgium"},{"name":"Belgium and Luxembourg Gynaecological Oncology Group (BGOG)  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Bouberhan","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Zajic","sequence":"additional","affiliation":[{"name":"Affiliation at time of study GSK  Collegeville PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murad","family":"Melhem","sequence":"additional","affiliation":[{"name":"GSK  Waltham MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Buscema","sequence":"additional","affiliation":[{"name":"TMC Healthcare Cancer Center  Tucson AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21763"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2024.05.546"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2216334"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2302312"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/19420862.2021.1954136"},{"key":"e_1_2_12_8_1","unstructured":"Jemperli. Package insert. GSK;2024."},{"key":"e_1_2_12_9_1","unstructured":"NICE. Dostarlimab for previously treated advanced or recurrent endometrial cancer with high microsatellite instability or mismatch repair deficiency.2024. Accessed October 3 2024.https:\/\/www.nice.org.uk\/guidance\/ta963\/resources\/dostarlimab\u2010with\u2010platinumbased\u2010chemotherapy\u2010for\u2010treating\u2010advanced\u2010or\u2010recurrent\u2010endometrial\u2010cancer\u2010with\u2010high\u2010microsatellite\u2010instability\u2010or\u2010mismatch\u2010repair\u2010deficiency\u2010pdf\u201082615787788741"},{"key":"e_1_2_12_10_1","unstructured":"GSK. Jemperli (dostarlimab for injection) plus carboplatin and paclitaxel approved in Canada as a treatment option for primary advanced or recurrent dMMR\/MSI\u2010H endometrial cancer.2023. Accessed October 3 2024.https:\/\/ca.gsk.com\/en-ca\/media\/press-releases\/jemperli-dostarlimab-for-injection-plus-carboplatin-and-paclitaxel-approved-in-canada-as-a-treatment-option-for-primary-advanced-or-recurrent-dmmrmsi-h-endometrial-cancer\/"},{"key":"e_1_2_12_11_1","unstructured":"GSK. GSK's Jemperli (dostarlimab) plus chemotherapy approved as the first and only frontline immuno\u2010oncology treatment in the European Union for dMMR\/MSI\u2010H primary advanced or recurrent endometrial cancer.2023. Accessed October 3 2024.https:\/\/www.gsk.com\/en-gb\/media\/press-releases\/jemperli-plus-chemotherapy-approved-as-the-first-and-only-frontline-immuno-oncology-treatment-in-the-european-union\/"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-019-00748-2"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.15339"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.16325"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-021-09739-y"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-016-0177-2"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw174"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2020.03.132"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-9966-31-50"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/17588359241277656"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.2174\/1574886313666180508122332"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1953"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.02132"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.70087","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpdd.70087","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.70087","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T12:24:00Z","timestamp":1787660640000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.70087"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":22,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/cpdd.70087"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.70087","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"2025-12-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70087"}}