Inhibrx's INBRX-106 Shows 44% Response Rate in Head and Neck Cancer Trial, Doubling Pembrolizumab Efficacy
Key Insights
INBRX-106 combined with pembrolizumab achieved a 44.0% confirmed objective response rate versus 21.4% with pembrolizumab alone in first-line head and neck squamous cell carcinoma patients.
The combination demonstrated superior depth of response with three complete radiographic responses and up to 15-fold increase in systemic T-cell expansion compared to pembrolizumab monotherapy.
The hexavalent OX40 (search) agonist showed a manageable safety profile with predominantly low-grade adverse events and no treatment-related deaths reported.
Inhibrx Biosciences reported positive interim Phase 2 results for INBRX-106, a hexavalent OX40 (search) agonist, showing the combination with pembrolizumab achieved a 44.0% confirmed objective response rate in first-line head and neck squamous cell carcinoma (HNSCC) patients, representing a 22.6% absolute increase over pembrolizumab monotherapy.
The randomized HexAgon study evaluated 68 patients with treatment-naïve, PD-L1 (search) positive (CPS ≥ 20) metastatic or unresectable recurrent HNSCC across over 80 sites in the United States, Europe and Asia. In the preliminary confirmed response-evaluable population of 53 patients, 11 out of 25 patients (44.0%) in the INBRX-106 combination arm achieved confirmed objective responses compared with 6 out of 28 patients (21.4%) receiving pembrolizumab alone.
Superior Clinical Outcomes and Mechanistic Evidence
The combination arm demonstrated notably deeper tumor reductions, with the majority of responding patients achieving target lesion shrinkage exceeding 50%. Three patients achieved complete radiographic responses in the combination arm, reflecting tumor clearance, while no complete responses were observed with pembrolizumab monotherapy. Complete responses in first-line HNSCC remain uncommon and are generally associated with more durable outcomes.
Pharmacodynamic analysis provided mechanistic support for the clinical activity, showing up to a 15-fold increase in peripheral CD8+ and CD4+ T-cell proliferation and up to a four-fold increase in activation in INBRX-106 combination-treated patients. In comparison, patients receiving pembrolizumab alone showed up to 2.5-fold and 1.5-fold increases in T-cell proliferation and activation, respectively.
Safety Profile and Tolerability
The combination demonstrated a manageable preliminary safety profile consistent with adding an active immunostimulatory agent to checkpoint blockade. The most common treatment-related adverse events were rash, diarrhea, fatigue, and infusion-related reactions, which were predominantly low-grade. No treatment-related deaths were reported in either arm.
Strategic Development Plans
Based on these results, Inhibrx plans to begin the Phase 3 portion of the HexAgon study during the third quarter of 2026. Progression-free survival data from the Phase 2 portion are expected in the fourth quarter of 2026.
The company aims to evaluate INBRX-106 across broader indications to potentially improve checkpoint inhibitor efficacy. This strategy includes initiating a study in the perioperative setting in non-small cell lung cancer (NSCLC) later this quarter, with expansion into front-line metastatic NSCLC expected to begin in 2027.
"We are greatly encouraged by these early clinical results," said Mark Lappe, Chief Executive Officer of Inhibrx. "These data, coupled with the clear evidence of T-cell expansion and superior depth of response, give us confidence that INBRX-106 could be the first costimulatory agent to fundamentally shift the efficacy ceiling of immunotherapy."
Technology Platform and Mechanism
INBRX-106 utilizes Inhibrx's proprietary single-domain antibody (sdAb) platform and is designed to achieve high-order receptor clustering necessary for robust T-cell activation and survival. This hexavalent approach addresses limitations that have challenged traditional bivalent antibody approaches in OX40 (search) targeting. To date, over 175 patients have been treated with INBRX-106.
The trial design was modeled after KEYNOTE-048, focusing on patients with high PD-L1 (search) expression to enhance the ability to detect treatment effects above checkpoint inhibition alone. HNSCC was selected as a proof-of-concept indication because PD-1 monotherapy shows activity in this tumor type but leaves significant room for improvement.