M7824 in People With Recurrent Respiratory Papillomatosis
Condition: Recurrent Respiratory Papillomatosis; Respiratory Papillomatosis; Laryngeal Papilloma, Recurrent; Human Papilloma Virus
MeSH terms: Respiratory Tract Infections; Papillomavirus Infections; Papilloma; Recurrence
Intervention: M7824
Intervention description: Patients will receive 1200 mg intravenous (IV) of M7824 on day 1 of a 14 day cycle, every other week, for up to 12 weeks total treatment (6 cycles).
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Human Papilloma Virus (HPV); Monoclonal Antibody; PD-L1 Expression

Summary:

      Background:

      Programmed cell death protein 1 (PD-L1) is a protein on the surface of cells. It regulates if
      a cell can be killed by immune system cells. It is thought to be able to affect the immune
      system response to diseased cells like those infected with a virus. The molecule M7824
      interferes with the activity of PD-L1. It could help the immune system kill cells infected
      with a virus . Since recurrent respiratory papillomatosis is caused by a virus infection,
      this molecule could help.

      Objective:

      To see if M7824 works in treating recurrent respiratory papillomatosis.

      Eligibility:

      Adults ages 18 years or older with recurrent respiratory papillomatosis

      Design:

      Participants will be screened with:

      Medical history

      Physical exam

      Blood and pregnancy tests

      Endoscopy procedure in clinic. A small tube with a camera will look at the inside of the
      nose, throat, larynx, and upper windpipe.

      Some participants will also be screened with a chest scan.

      At the start of the study, participants will:

      Have a sedated endoscopy procedure where biopsies will be taken.

      Have blood tests.

      Have apheresis. Blood will be collected by a tube in an arm vein. A machine will remove white
      blood cells. The rest of the blood will be returned into an arm vein.

      Fill out a voice questionnaire.

      Participants will get the study molecule into a vein over about 1 hour. They will get it
      every other week for up to 12 weeks.

      Participants will repeat screening and starting procedures throughout the study. They will
      also review side effects and any medicine they are taking.

      When they are done with the study treatment, participants will be evaluated by repeating the
      study procedures. They may be evaluated periodically until their disease progresses.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Recurrent Respiratory Papillomatosis (RRP) criteria:

          -  Histological diagnosis of RRP confirmed by pathology report from a Clinical Laboratory
             Improvement Amendments (CLIA)-certified laboratory.

          -  One of the following:

               -  A Derkay anatomic score of 10 or greater and a history of two or more endoscopic
                  interventions in the last 12 months for control of RRP.

               -  Pulmonary RRP with pulmonary disease that is measurable by computed tomography
                  scan and evaluated by Response Evaluation Criteria in Solid Tumors (RECIST)
                  Criteria.

               -  Tracheal involvement with RRP that has required either two or more endoscopic
                  interventions in the last 12 months or a tracheostomy.

          -  Greater than or equal to 18 years of age.

          -  Able to understand and sign the Informed Consent Document.

          -  Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.

          -  Willing to undergo endoscopic evaluation with biopsies in compliance with this
             protocol.

          -  No systemic therapy for RRP for at least 3 half-lives of the prior drug(s).

          -  Screening laboratory values must meet the following criteria and should be obtained
             within 14 days prior to first dose:

               -  White Blood Count (WBC) > 2000/ microliter

               -  Neutrophils > 1000/ microliter

               -  Platelets > 75 x10(3)/ microliter

               -  Hemoglobin > 9.0 g/dL

               -  Serum Creatinine < 1.5 x upper limits of normal (ULN) OR estimated glomerular
                  filtration rate (eGFR) > 30 mL/min (measured or calculated using the Modification
                  of Diet in Renal Disease (MDRD) equation).

               -  Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) less than or
                  equal to 2.5 x ULN

               -  Total Bilirubin: 1.5 x ULN

               -  Prothrombin time (PT)/International Normalized Ratio (INR) and partial
                  thromboplastin time (PTT) less than or equal to ULN

          -  Sexually active subjects (men and women) of reproductive potential must agree to use
             two methods of contraception: one highly effective and one other effective method
             throughout M7824 treatment and for at least 120 days after M7824 treatment. Highly
             Effective Methods are defined as: Intrauterine device (IUD), hormonal (birth control
             pills, injections, implants), tubal ligation and partner s vasectomy; Other are
             defined as: latex condom, diaphragm and cervical cap.

          -  Seronegative for human immunodeficiency virus (HIV) antibody. The experimental
             treatment being evaluated in this protocol depends on an intact immune system.
             Patients who are HIV seropositive can have decreased immune function and thus are
             likely less responsive to the experimental treatment.

          -  Seronegative for hepatitis B antigen, positive hepatitis B tests can be further
             evaluated by confirmatory tests (Hep B Deoxyribonucleic acid (DNA) Quant, hepatitis B
             virus (HBV) Viral Load), and if confirmatory tests are negative, the patient can be
             enrolled.

          -  Seronegative for hepatitis C antibody unless antigen negative. If hepatitis C antibody
             test is positive, then patients must be tested for the presence of antigen by Hep C
             Ribonucleic acid (RNA) Quant, hepatitis C virus (HCV) Viral Load and be HCV RNA
             negative.

        EXCLUSION CRITERIA:

          -  Any severe acute or chronic medical or psychiatric conditions including recent (within
             the past year) or active suicidal ideation or behavior, liver disease, lung disease
             (with the exception of what is specified in inclusion criteria) , or laboratory
             abnormalities that, in the opinion of the investigators, may increase the risk
             associated with study participation or study drug administration, impair the ability
             of the subject to receive protocol therapy, or interfere with the interpretation of
             study results and in the judgment of the investigator, would make the patient
             inappropriate for entry into this study. Patients with mild to moderate asthma or
             chronic obstructive pulmonary disease (COPD) well controlled with oral or inhaled
             medications are permitted to enroll.

          -  Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo,
             residual hypothyroidism due to autoimmune condition only requiring hormone
             replacement, or psoriasis not requiring systemic treatment, are permitted to enroll.

          -  Subjects with a condition requiring systemic treatment with either corticosteroids (>
             10 mg daily prednisone equivalents) or other immunosuppressive medications within 14
             days of study drug administration. Inhaled, topical intranasal or intro-ocular
             steroids, and adrenal replacement doses <10 mg daily prednisone equivalents are
             permitted in the absence of active autoimmune disease.

          -  Prior organ transplantation, including allogeneic stem cell transplantation.

          -  Patients who are receiving any other investigational agents

          -  Pregnant or breast feeding. Women of childbearing potential must have a negative
             pregnancy test at screening. Women of childbearing potential include women who have
             experienced menarche and who have not undergone successful surgical sterilization
             (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not
             postmenopausal. Post-menopause is defined as amenorrhea greater than or equal to 12
             consecutive months. Note: women who have been amenorrheic for 12 or more months are
             still considered to be of childbearing potential if the amenorrhea is possibly due to
             prior chemotherapy, anti- estrogens, ovarian suppression or any other reversible
             reason.

          -  History of allergy to study drug components.

          -  History of severe hypersensitivity reaction to any monoclonal antibody (Grade greater
             than or equal to 3 National Cancer Institute (NCI)-Common Terminology Criteria for
             Adverse Events (CTCAE) v 5.0), any history of anaphylaxis, or uncontrolled asthma
             (that is, 3 or more features of partially controlled asthma).

          -  Clinically significant (i.e., active) cardiovascular disease: cerebral vascular
             accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months
             prior to enrollment), unstable angina, congestive heart failure (greater than or equal
             to New York Heart Association Classification Class II), or serious cardiac arrhythmia
             requiring medication.

          -  Persisting toxicity related to prior therapy of Grade >1 NCI-CTCAE v 5.0; however,
             alopecia, sensory neuropathy Grade less than or equal to 2 or other Grade less than or
             equal to 2 adverse events (AEs) not constituting a safety risk based on investigator's
             judgment are acceptable.

          -  Known alcohol or drug abuse.

          -  Vaccination within 4 weeks of the first dose of M7824 and 4 weeks after the last dose
             of M7824 are prohibited.

          -  Human papillomavirus (HPV) vaccination within one year of the first dose of M7824

          -  With amendment D, patients that received prior Programmed cell death protein 1 (PD-1)
             based immunotherapy will be excluded.