INBRX-106/Pembrolizumab Shows Efficacy in First-Line HNSCC

Treatment with the investigational hexavalent OX40 agonist INBRX-106 plus pembrolizumab (Keytruda) nearly doubled the confirmed objective response rate (cORR) compared with pembrolizumab alone in patients with previously untreated, PD-L1–positive recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).¹

The primary end point findings from the randomized phase 2 portion of the HexAgon study (NCT06295731) show a cORR of 48.3% among patients who received the combination vs 26.5% for those treated with pembrolizumab monotherapy at the August 19, 2026 data cutoff. Four patients (13.8%) in the combination arm achieved a complete response (CR), whereas no CRs were observed in the control arm. Earlier interim findings from HexAgon reported in May 2026 also showed a higher response rate with the combination.

The treatment effect was particularly pronounced among patients with human papillomavirus (HPV)-positive disease. In this subgroup, the cORR was 80.0% with INBRX-106 plus pembrolizumab compared with 33.3% with pembrolizumab alone. CRs occurred in 30.0% of patients receiving the combination compared with none of those in the control group.

Median progression-free survival (PFS), which remains immature, was 9.6 months with the combination compared with 4.9 months with pembrolizumab alone. Six-month PFS rates were 72.4% and 42.8%, respectively.

Regarding safety, the combination was described as generally manageable. The most common treatment-related adverse events were rash, fatigue, and diarrhea, which were predominantly low grade.

"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 CEO of Inhibrx, stated in a news release. "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."

The current findings provide an early indication that OX40-mediated T-cell costimulation may enhance responses to PD-1 blockade, particularly in HPV-positive disease. However, the phase 2 analysis included a relatively small patient population, and median PFS remains immature. Additional enrollment and subsequent phase 3 evaluation will be needed to further characterize the efficacy and safety of the combination and establish its potential role in the treatment of HNSCC.

HexAgon Trial Background

HexAgon is a randomized, controlled phase 2 study evaluating the safety and efficacy of INBRX-106 in combination with pembrolizumab vs pembrolizumab monotherapy in the first-line setting for patients with treatment-naive, PD-L1–positive (combined positive score [CPS] ≥20) metastatic or unresectable recurrent HNSCC.² The study is being conducted at more than 80 sites across the United States, Europe, and Asia.

The randomized phase 2 portion of HexAgon enrolled 68 patients, of whom 63 were evaluable for the primary endpoint analysis. The combination arm included 29 patients, including 10 with HPV-positive disease, while the pembrolizumab-alone arm included 34 patients, including 9 with HPV-positive disease.

Earlier phase 1 findings evaluated INBRX-106 in combination with pembrolizumab across patients with locally advanced or metastatic solid tumors, with a maximum tolerated dose of 0.1 mg/kg every 3 weeks identified for the combination.

Next Steps in Development

Based on the phase 2 findings, the sponsor plans to expand the randomized portion of HexAgon by approximately 50 additional patients with HPV-positive oropharyngeal squamous cell carcinoma and a CPS of at least 1, intended to support a potential accelerated regulatory pathway. Following the phase 2 expansion, the sponsor plans to discuss the development framework with the FDA and initiate the phase 3 portion of HexAgon as a confirmatory study.

REFERENCES

1. 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. September 8, 2026. Accessed September 10, 2026. https://tinyurl.com/44kkxwrb

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 10, 2026. https://clinicaltrials.gov/study/NCT06295731