Exposure-Response Relationship of Dostarlimab in Primary Advanced/Recurrent Endometrial Cancer: Results From Interim Analysis 2 of Part 1 of the RUBY Trial.

Authors

Mita Kuchimanchi, Trine Lembrecht Jørgensen, Eva Hanze, Angela Jain, Oskar Alskär, Oleksandr Zub, Mark S Shahin, Anthoula Koliadi, Bhavana Pothuri, Thomas Krivak, Mikalai Pishchyk, Yakir Segev, Floor J Backes, Christine Gennigens, Sara Bouberhan, Stefan Zajic, Murad Melhem, Joseph Buscema

Published in

Clinical pharmacology in drug development. Volume 15. Issue 8. Pages e70087.

Abstract

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.

PMID:
42555284
Bibliographic data and abstract were imported from PubMed on 06 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.