Phase 2 Study of OBP-301 (Telomelysin™) in Combination With Pembrolizumab and SBRT in Patients With HNSCC With Inoperable, Recurrent or Progressive Disease
Condition: Head and Neck Squamous Cell Carcinoma With Inoperable Recurrent or Progressive Disease
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Recurrence; Disease Progression
Intervention: OBP-301; Pembrolizumab
Intervention description: Telomerase-specific Type 5 Adenovirus. OBP-301 OBP 301 will be injected intratumorally into tumor lesions.; Standard dose pembrolizumab 200 mg IV every 3 weeks for up to one year
Intervention MeSH terms: Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Head and Neck; Recurrent; Cure; Unresectable; Immunotherapy; Oncolytic Virus; SBRT; Intratumoral injection

Summary:

      The purpose of this study is to test the effects, of the research study drug Telomelysin
      (OBP-301) in combination with pembrolizumab in subjects with inoperable, recurrent, or
      progressive squamous cell carcinoma of the head and neck. Telomelysin is an investigational
      treatment, while pembrolizumab and SBRT are approved standard treatments. The combination of
      these three treatments is also considered investigational.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Be willing and able to provide written informed consent/assent for the trial.

          -  Be >18 years of age on the day of signing the informed consent.

          -  Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          -  Have histologically or cytologically confirmed advanced head and neck squamous cell
             cancer with cutaneous, subcutaneous or nodal tumors deemed as injectable lesions [see
             definition below] and have measurable disease for the primary study endpoint of
             overall response rate by RECIST 1.1 and iRECIST.In addition they must have (A) A
             single measurable tumor at least 1 cm in size and amenable to intratumoral injection
             or (B) Multiple measurable tumors that in aggregate have a longest diameter of ≥ 10 mm

        Note: Injectable lesion definitions: lesions amenable to percutaneous approach, if
        technically feasible

          -  Recurrent and inoperable tumor, progressing after prior radiation with curative-intent
             for advanced disease (adjuvant or definitive with or without chemotherapy or
             cetuximab). No prior treatment for local regional recurrence (LRR).

          -  Tumors may be either HPV+ or HPV-.

          -  Tumor must be PD-L1 positive, defined as CPS ≥ 1.

          -  Be willing to provide tissue; newly obtained biopsy specimens or formalin-fixed,
             paraffin-embedded (FFPE) block specimens.

          -  Female subjects of childbearing potential have a negative urine or serum pregnancy
             test within 7 days prior to enrollment. If the urine test is positive or cannot be
             confirmed as negative, a serum pregnancy test will be required. It is allowed that the
             test at the same day at 7 days prior to enrollment. And male / female subjects of
             childbearing potential must agree to use an adequate method of contraception starting
             with signing the informed consent through 120 days after the last dose of study
             medication.

          -  Demonstrated adequate organ function as defined in following criteria. All screening
             labs should be performed within 14 days of enrollment. Note: Subject must not have
             taken transfusion, hematopoietic agent; granulocyte-colony stimulating factor (G-CSF)
             etc., and/or oxygen supplementation within 7 days before the screening labs.

               -  Absolute neutrophil count (ANC)>=1,000 /mm3

               -  Platelets>=100,000 /mm3

               -  Hemoglobin>=9.0 g/dL

               -  Serum total bilirubin<=2.0 mg/dL

               -  Aspartate aminotransferase (AST) (SGOT) and alanine aminotransferase (ALT) (SGPT)
                  <= 2.5x Upper limit of normal (ULN). For subjects with liver metastases<= 5x ULN.

               -  Serum creatinine<= 1.5 mg/dL; or if serum creatinine >1.5 mg/dL, measured or
                  calculated creatinine/clearance>=60 mL/min (Cockcroft-Gault formula).

          -  Life expectancy of ≥ 6 months from the first OBP-301 treatment.

          -  Understand the study requirements and the treatment procedures, and is willing to
             comply with all specified follow- up evaluations, and provides written informed
             consent before any study-specific tests or procedures are performed.

        Exclusion Criteria:

          -  Is currently participating and receiving study therapy or has participated in a study
             of an investigational agent and received study therapy within 2 weeks (chemotherapy,
             small molecule), or 3 weeks (antibody) of study Day 1.

          -  Has an active autoimmune disease that has required systemic treatment in past 2 years.

          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (greater
             than the equivalent of prednisone 20 mg/day) or any other form of immunosuppressive
             therapy within 7 days prior to study Day 1. Daily dose of maintenance prednisone 10mg
             or equivalent is allowable.

          -  Has known active central nervous system metastases and/or carcinomatous meningitis.

          -  Has a known additional malignancy that is progressing or requires active treatment,
             with the exception of stable/low grade tumors that are not expected to influence
             life-expectancy (e.g. skin SCC, basal cell, differentiated thyroid cancer, prostate
             cancer on hormonal therapy).

          -  Has received a live vaccine within 30 days of planned start of study therapy.

          -  Has a known history of Human Immunodeficiency Virus.

          -  Has known active Hepatitis B or Hepatitis C.

          -  Has known history of, or any evidence of active, non-infectious pneumonitis.

          -  Has an active infection requiring systemic therapy.

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

          -  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.

          -  Previous severe hypersensitivity to another monoclonal antibody.

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the subject's
             participation for the full duration of the trial, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator.

          -  Prior intolerance related to severe (>=grade 3) irAE to a prior anti-immune checkpoint
             inhibitor agent leading to discontinuation of anti-immune checkpoint inhibitor
             therapy.

          -  Any disorder or condition, or any medication that would put the patient at risk from
             bleeding after direct tumor injection.

          -  Not a candidate for SBRT given for potentially curative intent. All tumors must
             receive SBRT. For example, patients with locoregional neck recurrence without
             significant overlap with the previous radiation field, and who do not warrant SBRT for
             re-irradiation as per the treating radiation oncologist (e.g. out-of-field
             recurrence), will not be included in the study.

          -  Received prior immunotherapy with checkpoint inhibitors or other immunotherapy agents.