HexAgon-HN: A phase 2/3 study of the hexavalent OX40 agonist ordastobart (INBRX-106) in combination with pembrolizumab as first-line treatment (1L tx) of PD-L1– high recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) - Phase 2 primary analysis

HexAgon-HN

Patient / Population Intervention / Exposition Vergleich Endpunkt

In patients with previously untreated recurrent or metastatic head and neck squamous cell carcinoma and PD-L1 CPS ≥20, ordastobart plus pembrolizumab increased the confirmed objective response rate compared with pembrolizumab alone.

N

68Patienten

Design

Phase 2 part of a phase 2/3 open-label trial in which patients with previously untreated recurrent or metastatic head and neck squamous cell carcinoma and PD-L1 CPS ≥20 were randomised 1:1 to ordastobart (INBRX-106) plus pembrolizumab or pembrolizumab alone (NCT06295731).

Endpunkt

Confirmed objective response rate by investigator per RECIST v1.1, with success defined as an observed ΔORR of ≥8 percentage points favouring ordastobart plus pembrolizumab.

ErgebnisIn response-evaluable patients (n=63), confirmed ORR was 48.3% (95% CI 29.4-67.5) with ordastobart plus pembrolizumab (n=29) vs 26.5% (95% CI 12.9-44.4) with pembrolizumab (n=34), an absolute ΔORR of 21.8%. In HPV+ disease, ORR was 80.0% (3 CR + 5 PR) with ordastobart plus pembrolizumab (n=10) vs 33.3% (3 PR) with pembrolizumab (n=9), a ΔORR of 46.7%. Preliminary PFS analyses suggested an improvement with the combination, but no PFS figures were reported. In the safety population (n=65), treatment-emergent AEs occurred in 100% vs 85.3%, grade ≥3 AEs in 58.1% vs 47.1% and serious AEs in 38.7% vs 35.3%. The most frequent treatment-related AEs with the combination (any grade/grade ≥3) were rash (32.3%/3.2%), rash maculo-papular (32.3%/9.7%), diarrhoea (29.0%/9.7%) and fatigue (29.0%/3.2%). Infusion-related reactions occurred in 22.6%/3.2%.

Park JC, Licitra LF, Kang EJ, et al. Presented at ESMO Congress 2026, abstract LBA42, 25 October. Not yet published.

Diskussion & Kritik

This small randomised phase 2 trial of 68 patients shows a higher investigator-assessed confirmed response rate when ordastobart is added to pembrolizumab, and the confidence intervals of the two arms overlap widely. Success was defined as an observed difference of at least 8 percentage points, not a formal hypothesis test, and no P value is given. The design was open label with investigator-assessed response, median follow-up was only 7.0 months and PFS is described as preliminary with no figures, so there is no evidence yet on time-to-event or survival outcomes. The larger effect in the HPV+ subgroup rests on 19 patients, and grade ≥3 and any treatment-emergent AEs were more frequent with the combination in this study funded by Inhibrx Biosciences.