INBRX-106 Plus Pembrolizumab Nearly Doubles Response Rate in HNSCC

INBRX-106, a hexavalent OX40 agonist, combined with pembrolizumab (Keytruda) nearly doubled the confirmed objective response rate (ORR) and extended progression-free survival (PFS) compared with pembrolizumab monotherapy in the phase 2 HexAgon-HN trial (NCT06295731), which is evaluating first-line treatment of PD-L1–positive metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC), according to a news release from the developer, Inhibrx Biosciences, Inc.¹

What were the interim phase 2 results from the HexAgon-HN trial?

At a data cutoff of August 19, 2026, the primary end point analysis showed a confirmed ORR of 48.3% with INBRX-106 plus pembrolizumab compared with 26.5% with pembrolizumab alone. Four patients (13.8%) in the combination arm achieved a complete response (CR) vs no CRs in the control arm. The median PFS, which the company noted continues to mature, was 9.6 months with the combination compared with 4.9 months with pembrolizumab alone; the 6-month PFS rates were 72.4% and 42.8%, respectively.

The combination of INBRX-106 and pembrolizumab was described as generally manageable. The most common treatment-related adverse effects were rash, fatigue, and diarrhea, which were predominantly low grade.

How did INBRX-106 perform in patients with HPV-positive disease?

The efficacy signal was most pronounced among patients with HPV-positive disease. In this subgroup, the combination arm achieved a confirmed ORR of 80.0% compared with 33.3% for pembrolizumab alone, and 30.0% of combination-treated patients achieved a CR vs none in the control arm. Ninety percent of patients with HPV-positive disease who received the combination remained progression free at 6 months compared with 33.0% who received pembrolizumab alone; the median PFS in the combination arm had not yet been reached vs 4.6 months for pembrolizumab alone.

“What is most exciting to us is the depth and durability of the responses we are seeing with INBRX-106, particularly in [HPV-positive] disease,” Mark Lappe, co-founder and chief executive officer of Inhibrx, said in the news release.¹ “These results strengthen our conviction in OX40-mediated T-cell costimulation and give us a strong rationale to expand the program, not only into [HPV-positive] disease, but also to explore the potential of INBRX-106 in other highly immunogenic tumors and in combination with cancer vaccines.”

What is the design of the HexAgon-HN trial?

The phase 2 portion of HexAgon-HN is a controlled study which randomly assigned patients to receive INBRX-106 plus pembrolizumab or pembrolizumab monotherapy for treatment-naive, PD-L1–positive metastatic or unresectable recurrent HNSCC considered incurable by local therapies. PD-L1 positivity was defined as a combined positive score (CPS) of 20 or greater.

Eligible patients had measurable disease per RECIST v1.1 criteria, a primary tumor in the oral cavity, oropharynx, hypopharynx, or larynx, and an ECOG performance status of 0 or 1; HPV status was determined by p16 immunohistochemistry testing.² Baseline prognostic factors were largely balanced between arms, and the study is being conducted at more than 80 sites across the US, Europe, and Asia.¹

Of 68 randomly assigned patients, 63 were evaluable for the primary end point analysis: 29 in the combination arm, including 10 with HPV-positive disease, and 34 in the control arm, including 9 with HPV-positive disease. The trial's PD-L1–positive enrollment population echoes that used in phase 3 KEYNOTE-048 protocol (NCT02358031), the trial that established pembrolizumab monotherapy as a first-line HNSCC option in this biomarker-selected subgroup.^2,3 The primary end point of the phase 2 portion was the confirmed ORR; secondary endpoints include duration of response, clinical benefit rate, quality of life, and safety.

What is INBRX-106, and what are the next steps for its development?

INBRX-106 is a hexavalent agonist antibody targeting OX40 (CD134), a costimulatory receptor on T cells. Built on the developer’s single-domain antibody platform, the drug is designed to achieve the high-order receptor clustering needed for robust T-cell activation and survival, an effect the company says traditional bivalent antibody approaches have not achieved.

Based on these results, Inhibrx plans to expand the randomized phase 2 portion of HexAgon-HN by approximately 50 additional patients with HPV-positive oropharyngeal squamous cell carcinoma, defined as a CPS of 1 or greater, to support a potential accelerated regulatory pathway. Following that expansion, the company plans to align with the FDA on this framework before initiating the phase 3 portion of the trial as a confirmatory study.

References

1. Inhibrx Biosciences, Inc. Inhibrx's INBRX-106 nearly doubles response rate and achieves interim median PFS of 9.6 months in phase 2 HNSCC study. News release. Inhibrx Biosciences, Inc. September 8, 2026. Accessed September 8, 2026. https://tinyurl.com/m29fe642
2. INBRX-106 in combination with pembrolizumab in first-line PD-L1 CPS≥20 HNSCC (HexAgon-HN). ClinicalTrials.gov. Updated May 8, 2026. Accessed September 8, 2026. https://tinyurl.com/ybhx8afj
3. Harrington KJ, Burtness B, Greil R, et al. Pembrolizumab with or without chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma: updated results of the phase III KEYNOTE-048 study. J Clin Oncol. 2023;41(4):790-802. doi:10.1200/JCO.21.02508