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 1 (screen failure, SF). The pt on Rv achieved ctDNA clearance at Part D weeks 2 and 10 and remains recurrence-free with undetectable ctDNA 12 months post-Rv. G2 neck pain and edema and G1 fatigue were reported, leading to Rv discontinuation after 5 doses, all resolved. The 1 pt on Obs and 1 pt with SF did not clear ctDNA and showed radiological PD at 190 and 235 days, respectively. With median FU of 17. 7 months from end of Tx, 10/42 pts (24%) had PD. ctDNA was also detected in 7/42 (17%) at B FU1 (all had PD except pt on Rv) and 2/27 (7%) at Part E (one had PD, one recurrence-free). Sensitivity (SE) and Specificity (SP) of ctDNA to detect PD at B FU2 (excluding pt on Rv, N=41) were 50 and 100%; across any follow up (Part B or E), 70% and 97%, respectively. In HPV+ OPC (N=16), HPV DNA showed a higher SE (100%) but lower SP (62%) at part B FU2. Further analysis with RaDaR and HPV-sequencing of remaining Part E samples is ongoing and will be presented. Conclusion: This is the first MRD interception study in LA-HNSCC. Although the study is on hold due to lower than expected MRD detection rates, we provide proof of concept for the value of interception using Rv. MERIDIAN has been amended to use a potentially more sensitive approach, including more frequent longitudinal plasma sampling, to improve MRD detection and interception. Citation Format: Enrique Sanz Garcia, Anna Spreafico, Ali Hosni, John De Almeida, Andrew McPartlin, Lawson Eng, David Goldstein, Andrew Hope, Christopher Yao, Ezra Hahn, John Waldron, Ilan Weinreb, Sakina Hussain, Patricia Inocillas, Lee Krug, Darren Hodgson, Bana Ambasager, Christopher G. Smith, Scott V. Bratman, Lillian L. Siu. Molecular residual disease (MRD) interception in locoregionally advanced head and neck squamous cell carcinoma (LA-HNSCC): The MERIDIAN Phase II trial abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86 (8Suppl): Abstract nr CT173.