Study of Intratumoral (IT) Ulevostinag (MK-1454) in Combination With Intravenous (IV) Pembrolizumab (MK-3475) Compared to IV Pembrolizumab Alone as the First Line Treatment of Metastatic or Unresectable, Recurrent Head and Neck Squamous Cell Carcinoma (HNSCC) (MK-1454-002)
Condition: Head and Neck Squamous Cell Carcinoma (HNSCC)
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
Intervention: Ulevostinag; Pembrolizumab
Intervention description: IT injection; IV infusion
Intervention MeSH terms: Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Programmed Cell Death-1 (PD1, PD-1); Programmed Death-Ligand 1 (PDL1, PD-L1); intratumoral (IT); metastatic; unresectable; recurrent; ulevostinag; pembrolizumab

Summary:

      The purpose of this study is to assess the efficacy and safety of intratumoral (IT)
      ulevostinag PLUS pembrolizumab (MK-3475) compared to pembrolizumab alone as a first line
      treatment of adults with metastatic or unresectable, recurrent head and neck squamous cell
      carcinoma (HNSCC).

      The primary study hypotheses are that IT ulevostinag in combination with pembrolizumab
      results in a superior Objective Response Rate (ORR), per Response Evaluation Criteria in
      Solid Tumors Version 1.1 (RECIST 1.1), compared to pembrolizumab alone:

        1. In participants with a tumor that has a programmed cell death-ligand 1 (PD-L1) Combined
           Positive Scoring (CPS) ≥ 1, and

        2. In participants with a tumor that has a PD-L1 CPS ≥ 20.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Has histologically or cytologically confirmed diagnosis of metastatic or unresectable,
             recurrent head and neck squamous cell carcinoma (HNSCC) that is considered incurable
             by local therapies

          -  Has not had prior systemic therapy administered in the recurrent or metastatic setting

          -  Has tumor PD-L1 expression of CPS ≥1. Tumor tissue must be provided for PD-L1
             biomarker analysis

          -  Has measurable disease per RECIST 1.1, as assessed by BICR

          -  Has at least 1 measurable lesion which is amenable to injection

          -  Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

          -  Demonstrates adequate organ function within 7 days prior to treatment initiation

          -  Male participants of reproductive potential must agree to refrain from donating sperm
             and use a male condom plus partner use of an additional contraceptive method during
             sexual contact with females of childbearing potential during the intervention period
             with ulevostinag and for at least 120 days after the last dose of ulevostinag

          -  Female participants of childbearing potential who are not pregnant or breastfeeding
             must be willing to use a highly effective method of birth control or be surgically
             sterile or abstain from heterosexual activity during the intervention period and for
             at least 120 days after the last dose of study intervention, and agree not to donate
             eggs (ova, oocytes) to others or freeze/store for personal use

          -  Human immunodeficiency virus (HIV)-infected participants must meet these additional
             criteria:

               1. Has HIV-1 infection documented by using any licensed rapid HIV test or HIV enzyme
                  or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study
                  entry (Day 1)

               2. Has well-controlled HIV on anti-retroviral therapy (ART)

        Exclusion Criteria:

          -  Has disease that is suitable for local therapy administered with curative intent

          -  Has progressive disease (PD) within 6 months of completion of curatively intended
             systemic treatment for locoregionally advanced HNSCC

          -  Has had chemotherapy or biological cancer therapy in the recurrent or metastatic
             setting for the treatment of HNSCC

          -  Has had radiation therapy (or other non-systemic therapy) within 2 weeks prior to
             randomization or participant has not fully recovered from adverse events (AEs) due to
             a previously administered treatment

          -  Is expected to require any other form of antineoplastic therapy while on study

          -  Has a history of a second malignancy, unless potentially curative treatment has been
             completed, with no evidence of malignancy for at least 2 years

          -  Has clinically active central nervous system (CNS) metastases and/or carcinomatous
             meningitis

          -  Has an active autoimmune disease that has required systemic treatment in the past 2
             years

          -  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

          -  Has had an allogenic tissue/solid organ transplant

          -  Has a history of vasculitis

          -  Has a history of interstitial lung disease

          -  Has an active infection requiring systemic therapy

          -  Has a known history of active tuberculosis (TB; Bacillus tuberculosis)

          -  Has a history of (non-infectious) pneumonitis that required steroids or current
             pneumonitis

          -  Has had a severe hypersensitivity reaction to treatment a monoclonal
             antibody/components of the study treatment

          -  Has known Hepatitis B virus or Hepatitis C virus infections

          -  Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1),
             anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-programmed cell death-ligand
             2 (anti-PD-L2) agent or if the participant has previously participated in Merck Sharp
             & Dohme (MSD) MK-3475 clinical trials

          -  HIV infected participant who has had an HIV-related opportunistic infection within 6
             months

          -  HIV infected participants who have a history of Kaposi's sarcoma and/or Multicentric
             Castleman's Disease

          -  Is pregnant, breastfeeding, or expecting to conceive or father children within the
             projected duration of the study, starting with the screening visit through 120 days
             after the last dose of study treatment

          -  Has not fully recovered from any effects of major surgery without significant
             detectable infection

          -  Has a history of re-irradiation for HNSCC at the projected injection site in the head
             and neck

          -  Has received a live-virus vaccine within 30 days of planned study treatment start

          -  Has been treated with a stimulator of interferon genes (STING) agonist (e.g.
             ulevostinag, ADU-S100)

          -  Is currently participating and receiving study therapy or has participated in a study
             of an investigational agent and received study therapy, or used an investigational
             device, any of which occurred within 4 weeks of the first dose of study treatment