In situ immune impact of nivolumab plus ipilimumab combination before standard chemoradiation therapy (RTCT) for FIGO IB3-IVA in patients (pts) with cervical squamous carcinoma: COLIBRI trial, a GINECO study

5501 Background: We report the results of a window-of-opportunity phase 2 trial using neoadjuvant nivolumab + ipilimumab followed by standard chemoradiation therapy (RTCT) in cervical squamous cell carcinoma pts using the CD8 + /FOXP3 + ratio as a surrogate marker of immune checkpoint blockade (ICB) in situ effect. Association with better clinical outcome after neoadjuvant chemotherapy and higher CD8 + /FOXP3 + ratio was described in cervical cancer pts. However, immune modulation after ICB and correlation with treatment response needs to be characterized. Methods: The primary objective was to explore the changes in the ratio of CD8 + /FOXP3 + in tumor biopsies performed before and after ICB (prior to standard RTCT) by multiplex-immunofluorescence (mIF) analyzing densities of CD8 effector T cells (CD8 + : CD3 + CD8 + FOXP3 - ) and CD4 regulatory T cells (FOXP3 + : CD3 + CD8 - FOXP3 + ). To normalize the distribution of the values, mIF data were log-transformed (log10). Targeted gene expression profiling of 2,549 genes using HTG technology allowed us to evaluate the 27-gene based ‘HOT’ score reported to be associated with immunologically active tumors (Foy J-P. et al., 2022, Eur J Can). Results: Pts received 1 cycle of nivolumab 3 mg/kg (D1D15) + ipilimumab 1 mg/kg (D1) before starting RTCT + brachytherapy. After RTCT, pts could continue nivolumab in maintenance 480 mg total dose every 28 days for 6 months. Forty pts were treated (including 50% FIGO III-IV). There were no new or unexpected toxicity. Grade≥3 AEs related to ICB occurred in 3 pts. mIF data of the 28 evaluable pts revealed an increase of total CD8 + cells (Wilcoxon, p=0.009), proliferating CD8 + cells (p=0.002) and CD8 + /FOXP3 + ratio (p=0.03) between baseline and before RTCT. In the 37 pts evaluable by HTG, a significant increase of expression of the CD8A gene (paired t-test, p=2.2e-05) and the ‘HOT’ score (paired t-test, p=3.1e-06) was observed after ICB. The Objective Response Rate on primary tumor before, after, at the end of treatment (EOT) is reported in table. Correlation between CD8 + /FOXP3 + ratio, the ‘HOT’ score and response to treatment will be presented. Conclusions: These data indicate that neoadjuvant nivolumab + ipilimumab is safe and orchestrates de novo immune responses in cervical squamous cell carcinoma. The 82.5% CR rate on primary tumor 6 months post RTCT suggests favorable clinical outcomes. Clinical trial information: NCT04256213 . [Table: see text]