22O Association of biomarkers with response to coformulated vibostolimab/pembrolizumab (vibo/pembro) in metastatic cervical cancer (CC): Exploratory analysis from the phase II KEYVIBE-005 study

In the multicohort KEYVIBE-005 study (NCT05007106), vibo/pembro (n = 85) showed antitumor activity similar to pembro (n = 84; ORR, 20.0% vs 15.5%) with a manageable safety profile in patients (pts) with previously untreated metastatic CC with PD-L1 CPS ≥1. We evaluated the association between biomarkers and response to treatment in this cohort. Using tumor samples, expression of TIGIT on immune cells (clone SP410, FLA assay) and PD-L1 CPS (PD-L1 22C3 pharmDx) were evaluated by IHC, T-cell–inflamed gene expression profile (TcellinfGEP) by NanoString, and TMB by WES. ORR and PFS were evaluated. Significance of continuous biomarkers was prespecified at 0.05 for 1-sided P values from logistic (ORR) and Cox proportional hazard (PFS) regression. ctDNA was isolated from pretreatment plasma samples collected on day 1 at cycle 1 (C1), C2, and C3 and sequenced using a personalized tumor-informed assay (Invitae PCM); quantity was expressed as maximum somatic allele frequency (MSAF). The association of biomarkers with ORR and PFS is reported in the table. The AUROCs (95% CI) for discriminating response to vibo/pembro were as follows: TIGIT, 0.64 (0.48-0.80); PD-L1, 0.72 (0.61-0.83); TcellinfGEP, 0.71 (0.56-0.86); and TMB, 0.74 (0.58-0.91). The AUROCs (95% CI) for discriminating response to pembro were as follows: TIGIT, 0.63 (0.47-0.79); PD-L1, 0.68 (0.50-0.86); TcellinfGEP, 0.65 (0.46-0.84); and TMB, 0.71 (0.46-0.95). Median ctDNA MSAF was reduced by 21% at C2 and by 32% at C3 with vibo/pembro (from C1) compared with 4% and 6% reductions, respectively, with pembro.Table: 22OP values of the association analysis between biomarkers and clinical outcomesVibo/pembroPembro monotherapyBiomarkernORRPFSnORRPFSTIGIT810.07400.0700800.0760.0270PD-L1 CPS850.00700.0002830.0110.2200TcellinfGEP740.00500.0003660.0600.0020TMB570.01200.1470530.0210.0004 Open table in a new tab In pts with CC with PD-L1 CPS ≥1, all biomarkers trended towards a positive association with response to vibo/pembro; the strongest associations were observed for PD-L1 and TcellinfGEP. Trends towards larger ctDNA decreases were observed with vibo/pembro vs pembro.