Overview

This seamless phase 2/3 randomized controlled study will evaluate the efficacy and safety of the hexavalent OX40 agonist antibody ordastobart (INBRX-106) combined with the anti-PD-1 antibody pembrolizumab versus pembrolizumab (+ placebo in phase 3) as first-line treatment for patients with recurrent or metastatic (R/M) HPV-positive Oropharyngeal Squamous Cell Carcinoma (HPV+ OPSCC) expressing PD-L1.

Eligibility

Inclusion Criteria:

• Has histologically or cytologically confirmed diagnosis of recurrent/metastatic oropharyngeal squamous cell carcinoma (OPSCC) considered incurable by local therapies.
• Has tumor PD-L1 expression with a combined proportion score (CPS) ≥1 by central testing.
• HPV-positive tumor status as assessed locally by p16 immunohistochemistry (IHC).
• Has measurable disease per RECIST 1.1 guidelines.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Exclusion Criteria:

• Has primary tumor site (any histology) of any other location than oropharynx.
• Has received prior systemic therapy (eg, prior chemo-, immune-, or biologic therapy) for R/M HNSCC.
  • Prior systemic therapy completed \>6 months prior to signing informed consent is allowed if given as part of multimodal treatment for locoregionally advanced disease with curative intent, and no PD/recurrence occurred within 6 months of its completion. Prior systemic immunotherapy with curative intent, including but not limited to anti-PD-(L)1 agents, is allowed if PD/recurrence occurred ≥12 months after its completion.
• Has clinically active central nervous system metastases and/or carcinomatous meningitis.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
• Rapidly progressing disease.
• Active or high risk of tumor-associated bleeding.
• Current or history of immune-related disease that required systemic treatment in past 2 years, except for replacement therapy.