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