Exposure-Response Relationship of Dostarlimab in Primary Advanced/Recurrent Endometrial Cancer: Results From Interim Analysis 2 of Part 1 of the RUBY TrialShow others and affiliations
2026 (English)In: Clinical Pharmacology in Drug Development, ISSN 2160-763X, E-ISSN 2160-7648, Vol. 15, no 8, article id e70087Article in journal (Refereed) Published
Abstract [en]
Dostarlimab in combination with carboplatin-paclitaxel 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-response (ER) relationship for progression-free survival or for the five most common dostarlimab-related adverse events (AEs), except rash. Herein, we report the ER relationship between dostarlimab exposure and overall survival (OS) and between dostarlimab exposure and dostarlimab-related 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 1-6 (chemotherapy phase), Cycle 7 and beyond (monotherapy phase), and all cycles. Included in the OS analysis were 232 patients treated with dostarlimab + carboplatin-paclitaxel. 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-paclitaxel as standard of care in patients with pA/rEC.
Place, publisher, year, edition, pages
John Wiley & Sons, 2026. Vol. 15, no 8, article id e70087
Keywords [en]
anticancer drugs, clinical pharmacology, drug safety, pharmacokinetics, therapeutics
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-596126DOI: 10.1002/cpdd.70087ISI: 001840432200001PubMedID: 42555284Scopus ID: 2-s2.0-105046599643OAI: oai:DiVA.org:uu-596126DiVA, id: diva2:2094625
2026-08-242026-08-242026-08-24Bibliographically approved