Emerging trends in research strategies in the first-line recurrent or metastatic head and neck cancer (R/M SCCHN) landscape: A top-level analysis by Oncofocus.

Abstract

e18029 Background: The current standard of care (pembrolizumab ± platinum-based chemotherapy and cetuximab + platinum-based chemotherapy) for the first-line (1L) treatment (Tx) of R/M SCCHN has set a median overall survival bar of ~13 months. Here, we present a top-level analysis of active regimens in this setting to identify emerging trends in research strategies aimed at improving the current benchmarks. Methods: Active regimens in the 1L R/M SCCHN space were identified from Oncofocus' internal knowledge base, which was developed through systematic screening of global clinical trial registries and validated using other authoritative sources. An analysis of the regimens was conducted to compile a list of unique therapeutic assets under evaluation. Emerging trends in targets and modalities were characterized based on key parameters, including trial phase and patient population. Results: With a data cut-off of Jan 19, 2026, 145 active regimens (111 unique assets) in the 1L R/M SCCHN pipeline landscape were included in this analysis. Across all ongoing studies, a total of 13 drug modalities are being evaluated, with the most common (≥5%) being monospecific antibody (37.8%, 42/111), small molecule (18.9%, 21/111), bispecific antibody (10.8%, 12/111), antibody-drug conjugate (10.8%, 12/111) and cancer vaccine (9.0%, 10/111). In terms of drug targets, 59 unique targets are being evaluated, with the most common being PD-1 (18.0%, 20/111), EGFR (12.6%, 14/111), and PD-L1 (7.2%, 8/111). Among the eight key Phase 3 trials (Table 1) that are evaluating novel combinations, all include PD-1 as one of the targets, aiming to build on the benefit seen with checkpoint blockade. Additionally, pembrolizumab is the preferred backbone agent (87.5%; 7/8) in these regimens. Conclusions: Current research trends indicate a shift in 1L Tx strategies for R/M SCCHN toward chemo-free combination therapies that target multiple pathways alongside PD-1 blockade. Additionally, future regulatory approvals may enable segmentation of the Tx algorithm based on key biomarkers, such as PD-L1 expression levels and HPV status. Key phase 3 trials in 1L R/M SCCHN. Trial acronym Regimen Targets Patient population Ph2/3 AHEAD-MERIT BNT113 + pembro HPV16 E6/7 + PD-1 HPV+, PD-L1 CPS ≥1 R/M SCCHN Ph3 ECLIPSE Cetuximab sarotalocan + pembro EGFR + PD-1 PD-L1 CPS ≥1, locoregional recurrent SCCHN Ph2/3 FORTIFI-HN01 Ficerafusp Alfa + pembro EGFR x TGF-β + PD-1 HPV–, PD-L1 CPS ≥1 R/M SCCHN Ph2/3 HexAgon-HN INBRX-106 + pembro OX40 + PD-1 PD-L1 CPS ≥20 R/M SCCHN Ph3 AK117-302 Ivonescimab + ligufalimab PD-1 x VEGF + CD47 PD-L1 CPS ≥1 R/M SCCHN Ph3 LiGeR-HN1 Petosemtamab + pembro EGFR x LGR5 + PD-1 PD-L1 CPS ≥1 R/M SCCHN Ph3 VERSATILE-003 Versamune HPV + pembro HPV16 E6/7 + PD-1 HPV+, PD-L1 CPS ≥1 R/M SCCHN Ph3 OrigAMI-5 Amivantamab + pembro + carboplatin EGFR x MET + PD-1 HPV–, R/M SCCHN