Inhibrx Biosciences (INBX) Study update summary

Study design and rationale

• Phase II HexAgon study evaluated INBRX-106 plus pembrolizumab versus pembrolizumab alone in first-line recurrent or metastatic HNSCC, with stratification by disease status, HPV status, and ECOG performance status.

• The study was designed as a seamless phase II/III program, enabling rapid transition to confirmatory trials and supporting potential breakthrough therapy designation.

• Primary endpoint was objective response rate (ORR); key secondary endpoints included duration of response, six-month progression-free survival (PFS), overall survival (OS), and safety.

• Patient arms were well-balanced for disease characteristics, including HPV status and PD-L1 expression.

• 68 patients were randomized, with 63 evaluable for the primary endpoint, across over 80 global sites.

Mechanism of action and biological validation

• INBRX-106 is a hexavalent OX40 agonist engineered to drive high-order receptor clustering, amplifying T-cell co-stimulation and activation.

• Addition of INBRX-106 to pembrolizumab led to up to a 15-fold increase in T-cell proliferation and up to a four-fold increase in T-cell activation.

• Enhanced activity was observed in both CD4+ and CD8+ T cells, crucial for anti-tumor immunity.

• Pharmacodynamic evidence confirmed INBRX-106 delivers the intended co-stimulatory biology.

• Utilizes a proprietary single-domain antibody platform for robust T-cell activation and survival, supporting rationale for vaccine combinations.

Efficacy results: overall and by HPV status

• INBRX-106 plus pembrolizumab achieved a confirmed ORR of 48.3% versus 26.5% for pembrolizumab alone, with a 21.8 percentage point improvement.

• Four complete responses were observed in the combination arm, none in the control; in HPV+ patients, combination therapy showed 80% ORR, 30% complete response, and 90% six-month PFS.

• Six-month PFS was 72.4% for the combination versus 42.8% for pembrolizumab alone; median PFS was 9.6 months (combination) versus 4.9 months (control).

• In HPV-negative patients, six-month PFS was 63% (combination) versus 46.8% (control), with median PFS of 7.5 months and 5.1 months, respectively.

• Efficacy in HPV-positive disease attributed to persistent viral antigens driving strong T-cell responses, amplified by OX40 co-stimulation.