Abstract Background: Measuring ctDNA is minimally invasive, has prognostic value, and can assess Tx response in cancer pts over time. The Phase 1 LuCa-MERIT-1 trial (NCT05142189) is evaluating BNT116, an IV administered investigational cancer immunotherapy comprising 6 lipoplexed, unmodified mRNAs each encoding a distinct tumor-associated antigen commonly overexpressed in NSCLC, ± combinations in pts with advanced NSCLC. We present ctDNA data from pts who received BNT116 + cemi (anti-PD-1 mAb). Methods: BNT116 was given QW during C1 and 2 and Q3W from C3 onwards (21 d cycles) ; cemi was given Q3W. Cell-free DNA was collected longitudinally and assessed with the Avenio ctDNA Surveillance Kit to determine ctDNA presence and estimate the VAF of somatic mutations. Associations between ctDNA levels, at BL and changes during Tx, with clinical outcomes (PFS, DDC, OS) were assessed with log-rank tests. Results: As of 01NOV25, 53 pts received BNT116 + cemi in Cohorts 1, 2 and 4 (Table 1). BL characteristics and clinical outcomes are shown in Table 1. ctDNA data were available from 51/53 pts (96%). Pts with lower ctDNA levels (max VAF split by median; n=25) at BL had improved PFS and OS, but not DDC; undetectable ctDNA at BL (n=12) was associated with improved OS, with a trend towards increased PFS. Analysis of outcomes in 39 pts with detectable ctDNA at BL indicated that achieving MR50 (n=20), typically seen after 6 wks on Tx, was associated with increased PFS, DDC and OS. Pts with ctDNA clearance at any timepoint (MR100; n=12) had similar OS to pts with undetectable ctDNA (n=10) at all timepoints. Conclusions: Achieving meaningful molecular responses early was associated with improved clinical outcomes after BNT116 + cemi Tx in pts with advanced NSCLC. Pts who achieved ctDNA clearance had similar outcomes to pts with undetectable ctDNA at BL. This supports use of ctDNA as a potential early efficacy surrogate in clinical trials, which can accelerate development of therapies. Citation Format: Janet L. Markman, Chiara Dalle Fratte, Chris D. Hermann, Maximilian Tator, Kathrin John, Kezi Ünsal-Kaçmaz, Victoria Chen, Manas Kumar Rout, Felicitas Tissen, Malgorzata Kaczorowska, Israel Lowy, Frank Seebach, Bala Başak Öven, Dániel Deme, Patrick Forde, Akin Atmaca, Michael Wenger, Özlem Türeci, Uğur Şahin, Patrick Brück, Rafal Dziadziuszko. ctDNA as a prognostic and pharmacodynamic biomarker following first- or later-line treatment of advanced NSCLC with BNT116 + cemiplimab 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 CT176.
Markman et al. (2026) studied this question.