Résumé
5502 Background: Treatment options for advanced endometrial cancer after failure of first-line chemotherapy are limited. In the KEYNOTE-158 study, pembro demonstrated durable antitumor activity (ORR, 48%; median DOR, not reached [NR]; median PFS, 13.1 mo; median OS, NR) and an acceptable safety profile in patients (pts) with previously treated advanced microsatellite instability-high/dMMR endometrial cancer. The immune checkpoints TIGIT and PD-L1 are upregulated in several tumor types, including endometrial cancer, and are heavily coexpressed in dMMR tumors, suggesting that dual TIGIT/PD-(L)1 blockade may be an effective therapeutic approach in advanced dMMR endometrial cancer. We present data from cohort B1 of the open-label phase 2 KEYVIBE-005 study (NCT05007106), which evaluated vibo/pembro (anti-TIGIT/anti–PD-1) in pts with previously treated advanced dMMR endometrial cancer. Methods: Eligible pts were aged ≥18 y with advanced dMMR endometrial cancer with progressive disease after 1 platinum-based chemotherapy regimen (or ≤2 lines if 1 was given in the [neo]adjuvant setting), no prior anti–PD-(L)1 therapy, and an ECOG PS of 0 or 1. Pts received vibo 200 mg coformulated with pembro 200 mg Q3W for ≤35 cycles (2 y). The primary end point was ORR per RECIST v1.1 by investigator assessment. Secondary end points included DOR and PFS per RECIST v1.1 by investigator assessment, OS, and safety. Results: A total of 40 pts were enrolled. Median age was 63 y and 60% of pts had ECOG PS 1; 31 pts had previously received 1 line of therapy in any setting and 9 pts had previously received ≥2 lines of therapy in any setting. The median time from first dose to data cutoff (Oct 24, 2023) was 17.2 mo (range, 7.7-23.4). At data cutoff, 23 pts had discontinued treatment and 17 were ongoing. The ORR was 65% (n = 26; 95% CI, 48-79); 5 pts (13%) had a complete response and 21 (53%) had a partial response. Median DOR was 13.7 mo (95% CI, 12.7-NR), and 75% of responders remained in response for ≥12 mo based on the Kaplan-Meier method for censored data. Median PFS was 15.0 mo (95% CI, 8.1-15.6) and the 12-mo PFS rate was 58%. Median OS was NR (95% CI, 16.1-NR) and the 12-mo OS rate was 82%. Treatment-related adverse events (AEs) occurred in 38 pts (95%). Grade 3 or 4 treatment-related AEs occurred in 14 pts (35%), of which the most common were arthritis (5%) and maculopapular rash (5%). Nine pts (23%) discontinued treatment due to a treatment-related AE. Any-grade immune-mediated AEs or infusion reactions occurred in 21 pts (53%) and grade 3 or 4 events occurred in 7 pts (18%). No deaths due to treatment-related AEs or immune-mediated AEs or infusion reactions occurred. Conclusions: Vibo/pembro demonstrated durable antitumor activity and a manageable safety profile in pts with previously treated advanced dMMR endometrial cancer. Clinical trial information: NCT05007106 .