Adding INBRX-106 to Pembrolizumab May Boost Outcomes in Frontline HNSCC

Combining the hexavalent OX40 agonist INBRX-106 with pembrolizumab (Keytruda) in the first-line setting elicited more than double the confirmed overall response rate (ORR) compared with using pembrolizumab alone in patients with treatment-naïve, PD-L1–positive (CPS ≥20) metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC), according to interim phase 2 results from the phase 2/3 HexAgon study.¹

Among evaluable patients treated with INBRX-106 plus pembrolizumab, the confirmed ORR was 44.0% (11 of 25 patients) compared to a confirmed ORR of 21.4% (6 of 28 patients) in the group receiving pembrolizumab alone.Three patients treated with the combination had a complete response compared with no patients in the control arm of single-agent pembrolizumab.

“We are greatly encouraged by these early clinical results," Mark Lappe, chief executive officer of Inhibrx, the developer of INBRX-106, stated in a news release.¹ "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, and open the door to combinations with new modalities that could be enhanced by OX40 agonism.”

HexAgon Study

Overall, the phase 2 portion of the HexAgon study accrued 68 patients with HNSCC, with 33 assigned to the INBRX-106 plus pembrolizumab arm and 35 assigned to the control arm of pembrolizumab alone. Prognostic characteristics for patients were generally well balanced between the treatment arms at baseline. The trial is being conducted at more than 80 clinical locations across the United States, Europe, and Asia.

At the May 7, 2026, data cutoff for the current analysis, there were 53 efficacy-evaluable patients, comprising 25 from the INBRX-106 combination arm and 28 from the control group. Assessment is ongoing for the remaining 15 patients enrolled in the trial across the 2 arms. Results for these patients will be included in a future efficacy analysis.

The primary end point of the phase 2 portion of HexAgon was ORR. Other outcome measures being assessed include duration of response, clinical benefit rate, quality of life, and safety.

The combination of INBRX-106 and pembrolizumab demonstrated a generally tolerable safety profile, aligning with expectations for the addition of an immunostimulatory therapy to checkpoint inhibition. The most frequently reported treatment-related adverse events included rash, diarrhea, fatigue, and infusion-related reactions, most of which were low grade in severity. No treatment-related fatalities occurred in either treatment arm.

Clinical Context of HexAgon Study Results

Among HNSCC patients with positive PD-L1 expression (CPS ≥1), single-agent pembrolizumab is a standard frontline regimen. In the KEYNOTE-048 trial, which supported the approval of pembrolizumab in this setting, the most robust benefit was observed in patients with CPS ≥20; however, the ORR in this group was still only 23%, meaning only about 1 in 4 patients responded.²

The HexAgon study investigators modeled the trial after KEYNOTE-048, focusing on the CPS ≥20 population to test the hypothesis that INBRX-106 could act as a costimulatory agent with pembrolizumab. The 44% ORR with the combination vs the 21.4% rate in the pembrolizumab control arm may indicate that the investigational agent did just that.

Looking Ahead for INBRX-106

Inhibrx anticipates that progression-free survival results from the phase 2 component of the HexAgon trial will likely be available in the fourth quarter of this year, with the phase 3 part of HexAgon expected to launch in the third quarter of 2026.

The company also plans to explore the synergistic capacity of INBRX-106 to boost outcomes with checkpoint inhibitors in other tumor types, including non–small cell lung cancer.

References

1. Inhibrx Biosciences, Inc. Inhibrx reports interim phase 2 data for INBRX-106 in first-line HNSCC: initial results demonstrate potential costimulatory benefit over PD-1 monotherapy. Press Release. Published May 11, 2026. Accessed May 11, 2026. https://inhibrxbiosciences.investorroom.com/2026-05-11-Inhibrx-Reports-Interim-Phase-2-Data-for-INBRX-106-in-First-Line-HNSCC-Initial-Results-Demonstrate-Potential-Costimulatory-Benefit-Over-PD-1-Monotherapy

2. KEYTRUDA (pembrolizumab) [prescribing information]. Rahway, NJ: Merck Sharp & Dohme LLC; revised November 2025. Accessed May 11, 2026. https://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf