Abstract CT173: Molecular residual disease (MRD) interception in locoregionally advanced head and neck squamous cell carcinoma (LA-HNSCC): The MERIDIAN Phase II trial

Abstract Introduction: Detection of ctDNA after definitive treatment (MRD) is associated with recurrence in LA-HNSCC. Intercepting MRD before clinical progression (PD) remains unexplored. Rilvegostomig (Rv), a TIGIT/PD-1 bispecific antibody, may clear ctDNA post-treatment and delay recurrence, in patients with LA-HNSCC. Methods: MERIDIAN (NCT05414032) aimed to enroll 200 patients (pts) with high risk LA-HNSCC: stage III human papillomavirus (HPV) + or III-IVB HPV-. Part A: definitive therapy (Tx) comprising surgery (Sx) ± adjuvant therapy; radiation (RT); or chemoRT (CRT). ctDNA was monitored in real time using RaDaR, a tumor-informed, mutation-based assay, at baseline (T0), post-Sx and post-Tx (Part B) at 4-6 weeks (B FU1) and 8-12 weeks (B FU2). Part C: MRD+ pts (ctDNA+ at B FU2 and no PD) with PD-L1 CPS ≥ 1 were randomized 3:1 to receive Rv 750mg IV q3w x 6 or observation (Obs). Primary endpoint was ctDNA clearance in MRD+ pts (no ctDNA detection 2 and 10 weeks post-interception (Part D)). Pts with undetected ctDNA at B FU2 and no PD entered surveillance (Part E), where ctDNA at 2-6 months was retrospectively analyzed. HPV DNA in plasma was analyzed retrospectively using HPV-sequencing. Results: 52 pts were screened, 46 enrolled; most had oropharyngeal cancer (OPC) (57%), stage III (54%), HPV- (57%), and received CRT (52%). ctDNA was detected in 38/39 (97%) with tumor in situ at T0. Concordance between plasma HPV at T0 and tissue HPV DNA in OPC was 100%. At B FU2, 42 pts were tested: 6 (14%) were ctDNA+, of whom 2 entered part C (1 received Rv, 1 Obs), 3 had PD at the end of Part B, and 1 was PD-L1