Intratumoral/Intralesional Administration of MK-4621/JetPEI™ With or Without Pembrolizumab in Participants With Advanced/Metastatic or Recurrent Solid Tumors (MK-4621-002)
Condition: Advanced Solid Tumors
MeSH terms: Neoplasms
Intervention: MK-4621; Pembrolizumab
Intervention description: MK-4621 is delivered via the JetPEI™ in vivo linear polyethylenimine nucleic acid delivery system as follows:
For Arm 1: administered intratumorally Q1W, on Days 1, 8, and 15 of each 21-day cycle.
For Arm 2: administered intratumorally Q1W, on Days 1, 8, and 15 of each 21-day cycle according to randomization.
For Arm 3: administered intratumorally Q3W, on Day 1 of each 21-day cycle. Range administered will depend upon allocation and be based on emerging safety data.; 200 mg administered intravenously (IV) on Day 1 of each 21-day cycle beginning with Cycle 1 (Arm 2) or Cycle 2 (Arm 3).
Intervention MeSH terms: Pembrolizumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Programmed Death-1 (PD-1, PD1),; Programmed Death-Ligand 1 (PD-L1, PDL1); Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)

Summary:

      The purpose of this study is to evaluate safety and tolerability, pharmacokinetics (PK), and
      preliminary antitumor activity of intratumoral (IT) / intralesional injections of MK-4621
      delivered via the JetPEI™ in vivo linear polyethylenimine nucleic acid delivery system as
      monotherapy and in combination with pembrolizumab in participants with advanced/metastatic
      solid tumors.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Has a histologically- or cytologically-confirmed advanced/metastatic solid tumor by
             pathology report and has received, or been intolerant to, all treatment known to
             confer clinical benefit

          -  Has submitted an evaluable baseline tumor sample for analysis before start of
             treatment

          -  Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
             Performance Scale

          -  Demonstrates adequate organ function

          -  Male participants must agree to use approved contraception during the treatment period
             and for at least 120 days after the last dose of study treatment and refrain from
             donating sperm during this period

          -  Female participants who are not pregnant or breastfeeding, and who are either not a
             woman of childbearing potential (WOCBP), or are a WOCBP who agrees to use approved
             contraception during the treatment period and for at least 120 days after the last
             dose of study treatment

        Arms 1 and 2: have 3 lesions defined as follows: 1) at least 1 cutaneous or subcutaneous
        lesion that is amenable to injection and biopsy (lesion 1) that is measurable as defined by
        RECIST 1.1, 2) at least 1 discrete non-injected, non-biopsied lesion that is measurable as
        defined by RECIST 1.1 (lesion 2), and 3) at least 1 discrete and/or distant non-injected
        lesion amenable for biopsy (lesion 3)

        Arm 3 only: Has metastatic liver and/or liver lesion involvement that does not exceed one
        third of the total liver volume in participants to be treated by liver IT injection.
        Hepatocellular carcinoma participants are excluded from eligibility of intratumoral liver
        injection. For Arm 3, at least 2 lesions have to be identified as follows: 1) at least 1
        liver lesion amenable to image-guided intratumoral injection and biopsy via ultrasound
        guidance or cross-sectional imaging (CT/MRI) guidance and must be measurable as defined by
        RECIST 1.1 (lesion 1) and 2) at least 1 other discrete non-injected, non-biopsied lesion
        that is measurable as defined by RECIST 1.1 (lesion 2)

        Exclusion Criteria:

          -  Has had chemotherapy, definitive radiation, or biological cancer therapy within 4
             weeks prior to the first dose of study therapy, or has not recovered to Common
             Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better from any AEs that
             were due to cancer therapeutics administered more than 4 weeks earlier

          -  History of a second malignancy, unless potentially curative treatment has been
             completed with no evidence of malignancy for 2 years

          -  Has hepatocellular carcinoma (for Arm 3 only)

          -  Has clinically active central nervous system (CNS) metastases and/or carcinomatous
             meningitis

          -  Has had a severe hypersensitivity reaction to treatment with a monoclonal
             antibody/components of the study treatment

          -  Has an active infection requiring therapy

          -  Has history of interstitial lung disease

          -  Has a history of (non-infectious) pneumonitis that required steroids or has current
             pneumonitis

          -  Has an active autoimmune disease that has required systemic treatment in past 2 years

          -  Has a known history of human immunodeficiency virus (HIV) infection and/or Hepatitis B
             or C infections, or known to be positive for Hepatitis B surface antigen
             (HBsAg)/Hepatitis B virus (HBV) DNA or Hepatitis C Antibody or RNA

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the study, interfere with the participant's
             participation for the full duration of the study, or is not in the best interest of
             the participant to participate, in the opinion of the treating investigator

          -  Has known psychiatric or substance abuse disorder that would interfere with
             cooperating with the requirements of the study

          -  Is pregnant or breastfeeding or expecting to conceive or father children within the
             projected duration of the trial, starting with the screening visit through 120 days
             after the last dose of trial treatment

          -  Has not fully recovered from any effects of major surgery without significant
             detectable infection

          -  WOCBP who has a positive urine pregnancy test within 72 hours before the first dose of
             study treatment

          -  Has received a live-virus vaccine within 30 days of planned treatment start

          -  Is currently participating in or has participated in a study of an investigational
             agent or has used an investigational device within 4 weeks prior to the first dose of
             study treatment. Prior exposure to immunotherapeutics is allowed, including PD-1 and
             PD-L1 inhibitors, provided participant did not experience a ≥Grade 3 drug-related
             toxicity on monotherapy with a PD-1 or PD-L1 inhibitor

          -  Has a history of re-irradiation for squamous cell carcinoma of head and neck (SCCHN)
             at the projected injection site

          -  Has a tumor(s) in direct contact or encases a major blood vessel and has ulceration
             and/or fungation onto the skin surface