Abstract 2412: Circulating HPV DNA as a potential biomarker to monitor response to the pembrolizumab and vorinostat combination in patients with squamous cell carcinoma of different locations

Abstract Background: The PEVOsq basket trial (NCT04357873) evaluated the efficacy of pembrolizumab and vorinostat (P+V) in patients (pts) with advanced squamous cell carcinoma (SCC) of different locationsAmong 112 pts included, 66 were HPV-positive (HPV+). Here we report HPV ctDNA monitoring in these pts. Methods: ctDNA before treatment (T0) and at first imaging (T1) from HPV+ SCC pts enrolled in the PEVOsq trial were analyzed using digital droplet PCR. Changes in HPV ctDNA levels between T0 and T1 were correlated to tumoral response (RECIST1.1). Landmark survival analyses were performed to study the association with progression free survival (PFS) and overall survival (OS). Results: Among the 66 HPV+ pts, 47 (71%) had plasma at T0 and T1. Most pts had anal (n=24, 51%) or cervix cancers (n=11, 23%), followed by vulva/vagina (n=8, 17%), penis (n=3, 6%) and head and neck (n=1, 2%) cancers. HPV ctDNA was detected in all 47 pts at baseline. Increasing HPV ctDNA copies at T1 correlated with progressive disease in 8 pts (67%), whereas decreasing HPV ctDNA occured in 6 (100%) and 8 (80%) pts with complete (CR) and partial response (PR), respectively (Table). Increase in HPV ctDNA copies were more frequent in non-responders pts versus responder pts (p=0.03) and was associated with shorter OS (12.1 months vs not reached, p=0.02) and a trend towards shorter PFS (4.3 versus 8.2 months, p=0.06). Taken as a continuous variable, 10% increase in HPV ctDNA between T0 and T1 was associated with higher risk of progression (HR=1.05; 95%CI, 1.02-1.08, p=0.0007) and shorter OS (HR=1.02; 95%CI, 1.01-1.03, p<0.0001) in univariate analysis. Table: Variation in HPV-ctDNA (N=47) Best response CR N=6 PR N=10 SD N=19 PD N=12 Increase 0 2 (20%) 6 (32%) 8 (67%) Decrease 6 (100%) 8 (80%) 13 (68%) 4 (33%) Conclusions: HPV ctDNA was detected at baseline in all pts reliably reflecting HPV detected on tissue. Dynamic changes in HPV ctDNA levels might help monitoring response to treatment in pts with advanced HPV+ cancers. Citation Format: Emmanuelle Jeannot, Daria Maria Filippini, Célia Dupain, Maral Halladjian, Grégoire Marret, Clélia Coutzac, Elodie Coquan, Mathilde Saint-Ghislain, Olivia Le Saux, Luca Mazzarella, Gianmaria Frige, Elena Guerini-Rocco, Miguel Francisco, Nicolas Servant, Maria Manuela Tonini, Laetitia Chanas, François Legrand, Stephan Bernhart, Gabor Balogh, Marta Jimenez, Ivan Bièche, Thomas Filleron, Bastien Cabarrou, Christophe Le Tourneau, Maud Kamal. Circulating HPV DNA as a potential biomarker to monitor response to the pembrolizumab and vorinostat combination in patients with squamous cell carcinoma of different locations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2412.