Clinical Trial Finder

Inclusion Criteria:

• - Has histologically or cytologically confirmed diagnosis of metastatic, recurrent head and neck squamous cell carcinoma (HNSCC) that is considered incurable by local therapies.

• - Has tumor PD-L1 expression of CPS ≥20.

Tumor tissue must be provided for PD-L1 biomarker analysis.

• - Has human papilloma virus (HPV) testing results for oropharyngeal cancer by p16 immunohistochemistry (IHC) testing.

• - Has measurable disease per RECIST 1.1 guidelines.

• - Has the primary tumor location of the oral cavity, oropharynx, hypopharynx, or larynx.

• - Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

• - Female patients of childbearing potential must have a negative highly sensitive pregnancy test within 72 hours prior to randomization and must not be breastfeeding.

• - Male and female patients of childbearing potential must be willing to completely abstain from heterosexual sex or agree to use a highly effective method of contraception.

Exclusion Criteria:

• - Has primary tumor site (any histology) of nasopharynx or salivary glands or occult primary site.

• - Has received prior systemic therapy (eg, prior chemo-, immune-, or biologic therapy) for locally advanced unresectable or metastatic 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 in the locoregionally advanced disease 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 or with features that may confer a high risk of tumor-associated hemorrhage or uncontrolled tumor pain.

• - Current or history of immune-related disease that required systemic treatment in past 2 years, except for replacement therapy.

Arms

Experimental: INBRX-106 plus pembrolizumab

Participants will receive INBRX-106 plus pembrolizumab, both given by intravenous (IV) infusion every 3 weeks (QW3)

Active Comparator: pembrolizumab monotherapy (+ placebo in phase 3 part)

Participants will receive pembrolizumab (plus placebo in Phase 3), given by intravenous (IV) infusion every 3 weeks (QW3)

Interventions

Drug: - INBRX-106

INBRX-106 by intravenous (IV) infusion, given every 3 weeks (QW3)

Drug: - Pembrolizumab

Pembrolizumab 200 mg by intravenous (IV) infusion, given every 3 weeks (QW3)