Pepinemab in Combination With Pembrolizumab in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

Inclusion Criteria

• •1. Subjects must be ≥18 years of age.
• •2. Subjects or their legal representative must be able to provide written informed consent to participate in the trial prior to the performance of any study-specific procedures.
• •3. Subjects must have histologically or cytologically confirmed HNSCC; eligible histologies include SCC of the oropharynx, oral cavity, hypopharynx, and larynx.
• •4. Subjects must have PD-L1 IHC (including CPS score using an FDA approved test) testing completed within 6 months of screening or at screening.
• •5. Have measurable disease per RECIST 1.1 as assessed by the central imaging vendor or the local site investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• •6. Subjects must have locally advanced, recurrent or metastatic neoplastic disease that is not curable by currently available local therapies.
• •7. Subjects must have an Eastern Cooperative Oncology Group (ECOG) PS of 0 or1.
• •8. Subjects must have a life expectancy of at least 12 weeks.
• •9. Subjects must have adequate hematologic reserve based on the following:
• •1. ANC ≥1,500/μL
• •2. Platelet count \>100,000/μL
• •3. Hemoglobin \>9 g/dL
• •10. Subjects must have adequate hepatic function based on the following:
• •1. Total bilirubin \<1.5 × upper limit of normal (ULN)
• •2. Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤2.5 x ULN (≤5 x ULN for subjects with known hepatic metastases).
• •11. Subjects must have adequate renal function based on the following:
• •1. Serum creatinine ≤1.5 × ULN; or
• •2. Calculated creatinine clearance of \>30 mL/min.
• •12. Human immunodeficiency virus (HIV) infected subjects must be on antiretroviral therapy (ART) and have a well-controlled HIV infection/disease defined as:
• •1. Subjects on ART must have a CD4+ T cell count 350 cells/mm3 at time of screening
• •2. Subjects on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 copies/mL or the lower limit of qualification (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks prior to screening
• •3. Subjects on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks prior to study entry (Day 1).
• •13. Subjects with oropharyngeal cancer must have archival tissue available for p16 testing or be willing to undergo pre-study biopsy to obtain tissue for p16 testing.
• •14. All subjects must have archival or recently obtained tissue available for biomarker analysis.
• •15. Female subjects of childbearing potential must have a negative pregnancy test within 72 hours of first dose of study treatment. Female subjects of childbearing potential must use a highly effective mode of contraception or abstain from heterosexual activity for the duration of the trial and for 120 days following the last dose of study medication. A female is NOT of childbearing potential if she has undergone bilateral salpingoophorectomy or is menopausal, defined as an absence of menses for 12 consecutive months. Male subjects must agree to use highly effective contraception.
• •Note: Subjects should remain on antiviral therapy throughout study intervention and follow local guidelines for HBV antiviral therapy post completion of study intervention.
• •Hepatitis B screening tests are not required unless:
• •1. Known history of HBV infection
• •2. As mandated by local health authority.
• •Hepatitis C screening tests are not required unless:
• •1. Known history of HCV infection
• •2. As mandated by local health authority.
• •19. Subjects who have received a live vaccine within 30 days of study enrollment.
• •20. Current alcohol or drug abuse.
• •21. Subjects with any intercurrent medical condition where the known risks of participation in the trial outweigh any potential benefits; subjects with psychiatric or social circumstances that preclude responsible participation in the trial; subjects with severe nutritional deficiencies or marked hypoalbuminemia.
• •22. History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the investigator (or designee).
• •23. Inability to comply with visit schedule or other protocol requirements.