<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03258008</url>
  </required_header>
  <id_info>
    <org_study_id>2017-0145</org_study_id>
    <nct_id>NCT03258008</nct_id>
  </id_info>
  <brief_title>Utomilumab and ISA101b Vaccination in Patients With HPV-16-Positive Incurable Oropharyngeal Cancer</brief_title>
  <official_title>Phase II Trial of Utomilumab and ISA101b Vaccination in Patients With HPV-16-Positive Incurable Oropharyngeal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>ISA Pharmaceuticals B.V.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>M.D. Anderson Cancer Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The goal of this clinical research study is to learn if utomilumab, when given with ISA101b,&#xD;
      is able to shrink or slow the growth of tumors in patients with incurable HPV+ oropharyngeal&#xD;
      squamous cell carcinoma.&#xD;
&#xD;
      This is an investigational study. Utomilumab and ISA101b are not FDA approved or commercially&#xD;
      available. They are currently being used for research purposes only. The study doctor can&#xD;
      explain how the study drugs are designed to work.&#xD;
&#xD;
      Up to 27 participants will be enrolled. All will take part at MD Anderson.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study Drug Administration:&#xD;
&#xD;
      There are 28 days in each study cycle.&#xD;
&#xD;
      You will receive utomilumab by vein every 4 weeks for up to 12 doses beginning on Cycle 1 Day&#xD;
      1. The drug will be given over about 1 hour each time you receive it.&#xD;
&#xD;
      You will receive ISA101b as an injection under the skin every 4 weeks for 3 doses. You will&#xD;
      receive 2 injections each time. One may be in your arm and one in your leg.&#xD;
&#xD;
      Length of Study:&#xD;
&#xD;
      You may continue taking utomilumab for up to 1 year as long as your doctor thinks it is in&#xD;
      your best interest. You will no longer be able to take the study drug(s) if intolerable side&#xD;
      effects occur or if you are unable to follow study directions. You may not be able to take&#xD;
      the study drug(s) if the disease gets worse, which is explained below.&#xD;
&#xD;
      Your participation on the study will be over after the follow-up visits.&#xD;
&#xD;
      Study Visits:&#xD;
&#xD;
      On Day 1 of Cycles 1-12:&#xD;
&#xD;
        -  You will have a physical exam.&#xD;
&#xD;
        -  Blood (about 1 tablespoon) will be collected for routine tests, thyroid function tests,&#xD;
           and liver function tests.&#xD;
&#xD;
        -  If you can become pregnant, blood (about ½ teaspoon) or urine will be collected for a&#xD;
           pregnancy test.&#xD;
&#xD;
        -  During Cycles 1, 2, 3, 4, 8, and 12, blood (up to 10 tablespoons) will be drawn for&#xD;
           biomarker testing (including genetic biomarkers).&#xD;
&#xD;
      At the end of Cycle 2 and every 8 weeks after that, you will have an MRI or CT scan to check&#xD;
      the status of the disease.&#xD;
&#xD;
      Study Continuation:&#xD;
&#xD;
      If the disease appears to have gotten worse, you may still be eligible to continue receiving&#xD;
      your assigned study drug(s). This is because you may be benefitting from the study drug(s)&#xD;
      even though the tumor(s) got larger. Your doctor will discuss this with you.&#xD;
&#xD;
      If this happens, your doctor will talk to you about whether or not you want to continue. If&#xD;
      you do continue taking part in the study, you will follow the study visits as described&#xD;
      above.&#xD;
&#xD;
      However, there are risks of continuing to receive the study drug(s) because the disease may&#xD;
      actually be getting worse. You are still at risk for side effects due to utomilumab and&#xD;
      ISA101b. Continuing on this study could also delay starting other treatments. The disease may&#xD;
      get worse to the point that you are no longer able to receive other treatments. There are&#xD;
      also risks from the additional tests that may be performed, such as biopsies and blood draws.&#xD;
      You and your doctor will discuss these possible risks, and you will be asked to decide if you&#xD;
      want to continue receiving the study drug(s).&#xD;
&#xD;
      End-of-Treatment and Follow-up Visits:&#xD;
&#xD;
      At about 30 days after your last study drug dose:&#xD;
&#xD;
        -  You will have a physical exam.&#xD;
&#xD;
        -  Blood (about 1 tablespoon) will be collected for routine tests, thyroid function tests,&#xD;
           and liver function tests.&#xD;
&#xD;
        -  If you are able to become pregnant, blood (about ½ teaspoon) or urine will be collected&#xD;
           for a pregnancy test.&#xD;
&#xD;
      At about 70 days after your last study drug dose:&#xD;
&#xD;
        -  You will have a physical exam.&#xD;
&#xD;
        -  Blood (about 1 tablespoon) will be collected for routine tests, thyroid function tests,&#xD;
           and liver function tests.&#xD;
&#xD;
        -  If you are able to become pregnant, blood (about ½ teaspoon) or urine will be collected&#xD;
           for a pregnancy test.&#xD;
&#xD;
      You will also be called every 3 months up to 1½ years and asked about your health. Each call&#xD;
      should last about 10-15 minutes.&#xD;
&#xD;
      If you stopped taking the study drug for reasons other than the disease getting worse, you&#xD;
      will continue to have MRI/CT scans every 8 weeks. If the disease appears to get worse, or you&#xD;
      start a new anticancer therapy, these scans will stop.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Closed the trial for infeasibility due to slow accrual&#xD;
  </why_stopped>
  <start_date type="Actual">April 4, 2018</start_date>
  <completion_date type="Actual">November 5, 2021</completion_date>
  <primary_completion_date type="Actual">November 5, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall Response Rate (ORR) of Utomilumab Combined With ISA 101b in Patients With Incurable Human Papillomavirus - Positive (HPV+) Oropharyngeal Squamous Cell Carcinoma (OPSCC)</measure>
    <time_frame>9 weeks from start of treatment</time_frame>
    <description>Overall Response Rate assessed by RECIST 1.1 Criteria</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse Events of Utomilumab Combined With ISA 101b in Patients With Incurable Human Papillomavirus - Positive (HPV+) Oropharyngeal Squamous Cell Carcinoma (OPSCC)</measure>
    <time_frame>Baseline, and continuously throughout the study at the beginning of each subsequent cycle up to 2 years</time_frame>
    <description>Adverse events assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for grades 1-3.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response Rate by irRC of Utomilumab Combined With ISA 101b in Patients With Incurable Human Papillomavirus - Positive (HPV+) Oropharyngeal Squamous Cell Carcinoma (OPSCC)</measure>
    <time_frame>Every-8-week schedule beginning from the first on-study assessment on Week 9 up to 2 years</time_frame>
    <description>Response rate monitored by radiographic assessment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS) of Utomilumab Combined With ISA 101b in Patients With Incurable Human Papillomavirus - Positive (HPV+) Oropharyngeal Squamous Cell Carcinoma (OPSCC)</measure>
    <time_frame>Every-8-week schedule beginning from the first on-study assessment on Week 9 up to 2 years</time_frame>
    <description>PFS defined as the time from first day of treatment to the date of the first documented tumor progression (per RECIST 1.1), or death due to any cause.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">3</enrollment>
  <condition>Malignant Neoplasms of Ill-defined Secondary and Unspecified Sites</condition>
  <condition>Malignant Neoplasms of Lip Oral Cavity and Pharynx</condition>
  <condition>Oropharyngeal Cancer</condition>
  <arm_group>
    <arm_group_label>Utomilumab + ISA101b</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Utomilumab by vein every 4 weeks for up to 12 doses beginning on Cycle 1 Day 1.&#xD;
ISA101b as an injection under the skin every 4 weeks for 3 doses. Participants receive 2 injections each time.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Utomilumab</intervention_name>
    <description>Utomilumab given by vein on Cycle 1 Day 1. Cycle 1-2 100 mg, Cycle 3-12 50 mg until progressive disease, toxicity, or 1 yr.</description>
    <arm_group_label>Utomilumab + ISA101b</arm_group_label>
    <other_name>PF-05082566</other_name>
    <other_name>Anti-CD137</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>ISA101b</intervention_name>
    <description>ISA101b 100 mcg/peptide given subcutaneously every 4 weeks x 3 doses beginning cycle 1 day 1.</description>
    <arm_group_label>Utomilumab + ISA101b</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subjects must have signed and dated an IRB/IEC approved written informed consent form&#xD;
             in accordance with regulatory and institutional guidelines. This must be obtained&#xD;
             before the performance of any protocol related procedures that are not part of normal&#xD;
             subject care.&#xD;
&#xD;
          2. Subjects must be willing and able to comply with scheduled visits, treatment schedule,&#xD;
             laboratory tests and other requirements of the study.&#xD;
&#xD;
          3. Men and women &gt;/= 18 years of age.&#xD;
&#xD;
          4. Eastern Cooperative Oncology Group (ECOG) performance status of &lt;/= 1.&#xD;
&#xD;
          5. Subjects with histologically- or cytologically-documented incurable Human&#xD;
             Papillomavirus (HPV)-positive OPSCC. HPV-16 serotype will be assessed by Cervista&#xD;
             assay.&#xD;
&#xD;
          6. Subjects can be treatment naïve or may have had two prior regimens for recurrent&#xD;
             cancer. They must be naive to treatment with PD-1/L1 or CTLA-4 inhibitors.&#xD;
&#xD;
          7. Subjects must have progression within 6 months of platin exposure during definitive or&#xD;
             palliative therapy.&#xD;
&#xD;
          8. Subjects must have measurable disease by CT or MRI per RECIST 1.1 criteria;&#xD;
             Radiographic Tumor Assessment performed within 28 days of study inclusion.&#xD;
&#xD;
          9. Target lesions may be located in a previously irradiated field if there is documented&#xD;
             (radiographic) disease progression in that site.&#xD;
&#xD;
         10. Subject entering the study will need to consent for mandatory biopsy at study entrance&#xD;
             and as an optional procedure prior to C3 for biomarker evaluation. Biopsy should be&#xD;
             excisional, incisional or core needle. Fine needle aspiration is insufficient.&#xD;
&#xD;
         11. Prior chemotherapy, monoclonal antibody therapy, must have been completed at least 4&#xD;
             weeks prior to start. Radiotherapy or radiosurgery must have been completed at least 2&#xD;
             weeks prior to start.&#xD;
&#xD;
         12. All baseline laboratory requirements will be assessed and should be obtained within&#xD;
             -14 days of study registration. Screening laboratory values must meet the following&#xD;
             criteria i) White blood cells (WBCs) &gt;/= 2000/microL ii) Neutrophils &gt;/= 1500/microL&#xD;
             iii) Platelets &gt;/= 100 x 10^3/microL iv) Hemoglobin &gt;/= 9.0 g/dL Patients must not be&#xD;
             transfused for at least 14 days prior to study entry v) Serum creatinine of &lt;/=1.5 x&#xD;
             upper limit of normal(ULN) or creatinine clearance(CrCl) &gt; 50 mL/minute (using&#xD;
             Cockcroft/Gault formula) Female CrCl= 0.85 x [(140 - age in years) x weight in kg]/(72&#xD;
             x serum creatinine in mg/dL) Male CrCl= 1.00 x [(140 - age in years) x weight in&#xD;
             kg]/(72 x serum creatinine in mg/dL) vi) AST &lt;/= 2.5 x ULN vii) ALT &lt;/= 2.5 x ULN&#xD;
             viii) Total bilirubin&lt;/= 1.5 x ULN (except subjects with Gilbert Syndrome who must&#xD;
             have total bilirubin &lt;3.0 mg/dl).&#xD;
&#xD;
         13. Women of childbearing potential (WOCBP) must use method(s) of contraception for 30&#xD;
             days + 5 half-lives (60 days) of the study drugs. For a teratogenic study drug and/or&#xD;
             when there is insufficient information to assess teratogenicity (preclinical studies&#xD;
             have not been done), a highly effective method(s) of contraception (failure rate of&#xD;
             less than 1% per year) is required. Highly effective birth control in this study is&#xD;
             defined as a double barrier method. Examples include a condom (with spermicide) in&#xD;
             combination with a diaphragm, cervical cap, or intrauterine device (IUD). The&#xD;
             individual methods of contraception should be determined in consultation with the&#xD;
             investigator.&#xD;
&#xD;
         14. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L&#xD;
             or equivalent units of HCG) within 24 hours prior to the start of investigational&#xD;
             product.&#xD;
&#xD;
         15. Women must not be breastfeeding.&#xD;
&#xD;
         16. Men who are sexually active with WOCBP must use any contraceptive method with a&#xD;
             failure rate of less than 1% per year. The investigator shall review contraception&#xD;
             methods and the time period that contraception must be followed. Men that are sexually&#xD;
             active with WOCBP must follow instructions for birth control for a period of 90 days&#xD;
             plus the time required for the investigational drug to undergo 5 half- lives (60&#xD;
             days).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects with active CNS metastases are excluded. Subjects are eligible if CNS&#xD;
             metastases are adequately treated and subjects are neurologically returned to baseline&#xD;
             (except for residual signs or symptoms related to the CNS treatment) for at least 4&#xD;
             weeks prior to enrollment. In addition, subjects must be either off corticosteroids,&#xD;
             or on a stable or decreasing dose of &lt;/= 10 mg daily prednisone (or equivalent) for 2&#xD;
             weeks.&#xD;
&#xD;
          2. Subjects with carcinomatous meningitis.&#xD;
&#xD;
          3. Subjects with active, known or suspected systemic autoimmune disease. Subjects with&#xD;
             vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune&#xD;
             thyroiditis only requiring hormone replacement, or conditions not expected to recur in&#xD;
             the absence of an external trigger are permitted to enroll.&#xD;
&#xD;
          4. Subjects with a condition requiring systemic treatment with either corticosteroids&#xD;
             (&gt;10 mg daily prednisone equivalent) or other immunosuppressive medications within 14&#xD;
             days of start. Inhaled or topical steroids, and adrenal replacement steroid doses &gt; 10&#xD;
             mg daily prednisone equivalent, are permitted in the absence of active autoimmune&#xD;
             disease.&#xD;
&#xD;
          5. Prior therapy with anti-CD137 or ISA101.&#xD;
&#xD;
          6. Subjects with a history of interstitial lung disease.&#xD;
&#xD;
          7. Other active malignancy requiring concurrent intervention.&#xD;
&#xD;
          8. Subjects with previous malignancies (except non-melanoma skin cancers, and the&#xD;
             following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia,&#xD;
             melanoma, or breast) are excluded unless a complete remission was achieved at least 2&#xD;
             years prior to study entry AND no additional therapy is required during the study&#xD;
             period.&#xD;
&#xD;
          9. Subjects with toxicities attributed to prior anti-cancer therapy other than alopecia&#xD;
             and fatigue that have not resolved to grade 1 (NCI CTCAE version 4.03) or baseline&#xD;
             before administration of study drug.&#xD;
&#xD;
         10. Subjects who have not recovered from the effects of major surgery or significant&#xD;
             traumatic injury at least 14 days before the first dose of study treatment.&#xD;
&#xD;
         11. Treatment with any investigational agent within 28 days of first administration of&#xD;
             study treatment.&#xD;
&#xD;
         12. Known history of testing positive for human immunodeficiency virus (HIV) or known&#xD;
             acquired immunodeficiency syndrome (AIDS).&#xD;
&#xD;
         13. Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus&#xD;
             ribonucleic acid (HCV RNA) indicating acute or chronic infection.&#xD;
&#xD;
         14. History of allergy or intolerance (unacceptable adverse event) to study drugs&#xD;
             components.&#xD;
&#xD;
         15. WOCBP who are pregnant or breastfeeding.&#xD;
&#xD;
         16. Women with a positive pregnancy test at enrollment or prior to administration of study&#xD;
             medication.&#xD;
&#xD;
         17. Any other serious or uncontrolled medical disorder, active infection, physical exam&#xD;
             finding, laboratory finding, altered mental status, or psychiatric condition that, in&#xD;
             the opinion of the investigator, would limit a subject's ability to comply with the&#xD;
             study requirements, substantially increase risk to the subject, or impact the&#xD;
             interpretability of study results.&#xD;
&#xD;
         18. Prisoners or subjects who are involuntarily incarcerated.&#xD;
&#xD;
         19. Subjects who are compulsorily detained for treatment of either a psychiatric or&#xD;
             physical (eg, infectious disease) illness.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bonnie S. Glisson, BS,MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Texas MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mdanderson.org</url>
    <description>University of Texas MD Anderson Cancer Center Website</description>
  </link>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>August 21, 2017</study_first_submitted>
  <study_first_submitted_qc>August 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 22, 2017</study_first_posted>
  <results_first_submitted>November 1, 2022</results_first_submitted>
  <results_first_submitted_qc>November 22, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">December 16, 2022</results_first_posted>
  <last_update_submitted>November 22, 2022</last_update_submitted>
  <last_update_submitted_qc>November 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 16, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Malignant neoplasms of lip oral cavity and pharynx</keyword>
  <keyword>Malignant neoplasms of ill-defined secondary and unspecified sites</keyword>
  <keyword>Oropharyngeal Cancer</keyword>
  <keyword>Oropharyngeal squamous cell carcinoma</keyword>
  <keyword>OPSCC</keyword>
  <keyword>Human Papillomavirus - positive (HPV+)</keyword>
  <keyword>Utomilumab</keyword>
  <keyword>PF-05082566</keyword>
  <keyword>Anti-CD137</keyword>
  <keyword>ISA101b</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Oropharyngeal Neoplasms</mesh_term>
    <mesh_term>Lip Neoplasms</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 20, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/08/NCT03258008/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Recruitment Period: April 2018 to February 2019-Closed the trial for infeasibility due to slow accrual</recruitment_details>
      <pre_assignment_details>3 Participants registered to the trial, 1 was not eligible as screen fail.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Utomilumab and ISA101b</title>
          <description>Treatment with Utomilumab every 4 weeks and 3 doses of ISA101b Vaccination for every 4 weeks first 3 cycles in Patients with HPV-16-Positive Incurable Oropharynx Cancer</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All participants who signed the consent are included in the baseline characteristics.</population>
      <group_list>
        <group group_id="B1">
          <title>Utomilumab and ISA101b</title>
          <description>Treatment with Utomilumab every 4 weeks and 3 doses of ISA101b Vaccination for every 4 weeks first 3 cycles in Patients with HPV-16-Positive Incurable Oropharynx Cancer</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="3"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Overall Response Rate (ORR) of Utomilumab Combined With ISA 101b in Patients With Incurable Human Papillomavirus - Positive (HPV+) Oropharyngeal Squamous Cell Carcinoma (OPSCC)</title>
        <description>Overall Response Rate assessed by RECIST 1.1 Criteria</description>
        <time_frame>9 weeks from start of treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Utomilumab and ISA101b</title>
            <description>Treatment with Utomilumab every 4 weeks and 3 doses of ISA101b Vaccination for every 4 weeks first 3 cycles in Patients with HPV-16-Positive Incurable Oropharynx Cancer</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Response Rate (ORR) of Utomilumab Combined With ISA 101b in Patients With Incurable Human Papillomavirus - Positive (HPV+) Oropharyngeal Squamous Cell Carcinoma (OPSCC)</title>
          <description>Overall Response Rate assessed by RECIST 1.1 Criteria</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>97.5% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0.0" upper_limit="0.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Adverse Events of Utomilumab Combined With ISA 101b in Patients With Incurable Human Papillomavirus - Positive (HPV+) Oropharyngeal Squamous Cell Carcinoma (OPSCC)</title>
        <description>Adverse events assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for grades 1-3.</description>
        <time_frame>Baseline, and continuously throughout the study at the beginning of each subsequent cycle up to 2 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Utomilumab and ISA101b</title>
            <description>Treatment with Utomilumab every 4 weeks and 3 doses of ISA101b Vaccination for every 4 weeks first 3 cycles in Patients with HPV-16-Positive Incurable Oropharynx Cancer</description>
          </group>
        </group_list>
        <measure>
          <title>Adverse Events of Utomilumab Combined With ISA 101b in Patients With Incurable Human Papillomavirus - Positive (HPV+) Oropharyngeal Squamous Cell Carcinoma (OPSCC)</title>
          <description>Adverse events assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for grades 1-3.</description>
          <units>adverse events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Response Rate by irRC of Utomilumab Combined With ISA 101b in Patients With Incurable Human Papillomavirus - Positive (HPV+) Oropharyngeal Squamous Cell Carcinoma (OPSCC)</title>
        <description>Response rate monitored by radiographic assessment.</description>
        <time_frame>Every-8-week schedule beginning from the first on-study assessment on Week 9 up to 2 years</time_frame>
        <population>No data collected for Response Rate by irRC of Utomilumab Combined with ISA 101b in Patients with Incurable Human Papillomavirus - Positive (HPV+) Oropharyngeal Squamous Cell Carcinoma (OPSCC).</population>
        <group_list>
          <group group_id="O1">
            <title>Utomilumab and ISA101b</title>
            <description>Treatment with Utomilumab every 4 weeks and 3 doses of ISA101b Vaccination for every 4 weeks first 3 cycles in Patients with HPV-16-Positive Incurable Oropharynx Cancer</description>
          </group>
        </group_list>
        <measure>
          <title>Response Rate by irRC of Utomilumab Combined With ISA 101b in Patients With Incurable Human Papillomavirus - Positive (HPV+) Oropharyngeal Squamous Cell Carcinoma (OPSCC)</title>
          <description>Response rate monitored by radiographic assessment.</description>
          <population>No data collected for Response Rate by irRC of Utomilumab Combined with ISA 101b in Patients with Incurable Human Papillomavirus - Positive (HPV+) Oropharyngeal Squamous Cell Carcinoma (OPSCC).</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression Free Survival (PFS) of Utomilumab Combined With ISA 101b in Patients With Incurable Human Papillomavirus - Positive (HPV+) Oropharyngeal Squamous Cell Carcinoma (OPSCC)</title>
        <description>PFS defined as the time from first day of treatment to the date of the first documented tumor progression (per RECIST 1.1), or death due to any cause.</description>
        <time_frame>Every-8-week schedule beginning from the first on-study assessment on Week 9 up to 2 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Utomilumab and ISA101b</title>
            <description>Treatment with Utomilumab every 4 weeks and 3 doses of ISA101b Vaccination for every 4 weeks first 3 cycles in Patients with HPV-16-Positive Incurable Oropharynx Cancer</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival (PFS) of Utomilumab Combined With ISA 101b in Patients With Incurable Human Papillomavirus - Positive (HPV+) Oropharyngeal Squamous Cell Carcinoma (OPSCC)</title>
          <description>PFS defined as the time from first day of treatment to the date of the first documented tumor progression (per RECIST 1.1), or death due to any cause.</description>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.84" lower_limit="1.84" upper_limit="NA">not estimable</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose of drug, unless the participant withdraws consent, through study completion an average of 24 months.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Utomilumab and ISA101b</title>
          <description>Treatment with Utomilumab every 4 weeks and 3 doses of ISA101b Vaccination for every 4 weeks first 3 cycles in Patients with HPV-16-Positive Incurable Oropharynx Cancer</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>1</frequency_threshold>
        <default_vocab>CTCAE (4.3)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Endocrine disorders - Other, specify Increased TSH Levels</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infections and infestations - Other, specify Rhinitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperuricemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pain of skin</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, specify pain at injection site</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. John Heymach, PHD-Chair, Thoracic-Head &amp; Neck Med Onc</name_or_title>
      <organization>UT MD Anderson Cancer Center</organization>
      <phone>(713) 792-6363</phone>
      <email>jheymach@mdanderson.org</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03258008
org study id: 2017-0145
nct id: NCT03258008
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The goal of this clinical research study is to learn if utomilumab, when given with ISA101b,
      is able to shrink or slow the growth of tumors in patients with incurable HPV+ oropharyngeal
      squamous cell carcinoma.

      This is an investigational study. Utomilumab and ISA101b are not FDA approved or commercially
      available. They are currently being used for research purposes only. The study doctor can
      explain how the study drugs are designed to work.

      Up to 27 participants will be enrolled. All will take part at MD Anderson.
Study Drug Administration:

      There are 28 days in each study cycle.

      You will receive utomilumab by vein every 4 weeks for up to 12 doses beginning on Cycle 1 Day
      1. The drug will be given over about 1 hour each time you receive it.

      You will receive ISA101b as an injection under the skin every 4 weeks for 3 doses. You will
      receive 2 injections each time. One may be in your arm and one in your leg.

      Length of Study:

      You may continue taking utomilumab for up to 1 year as long as your doctor thinks it is in
      your best interest. You will no longer be able to take the study drug(s) if intolerable side
      effects occur or if you are unable to follow study directions. You may not be able to take
      the study drug(s) if the disease gets worse, which is explained below.

      Your participation on the study will be over after the follow-up visits.

      Study Visits:

      On Day 1 of Cycles 1-12:

        -  You will have a physical exam.

        -  Blood (about 1 tablespoon) will be collected for routine tests, thyroid function tests,
           and liver function tests.

        -  If you can become pregnant, blood (about ½ teaspoon) or urine will be collected for a
           pregnancy test.

        -  During Cycles 1, 2, 3, 4, 8, and 12, blood (up to 10 tablespoons) will be drawn for
           biomarker testing (including genetic biomarkers).

      At the end of Cycle 2 and every 8 weeks after that, you will have an MRI or CT scan to check
      the status of the disease.

      Study Continuation:

      If the disease appears to have gotten worse, you may still be eligible to continue receiving
      your assigned study drug(s). This is because you may be benefitting from the study drug(s)
      even though the tumor(s) got larger. Your doctor will discuss this with you.

      If this happens, your doctor will talk to you about whether or not you want to continue. If
      you do continue taking part in the study, you will follow the study visits as described
      above.

      However, there are risks of continuing to receive the study drug(s) because the disease may
      actually be getting worse. You are still at risk for side effects due to utomilumab and
      ISA101b. Continuing on this study could also delay starting other treatments. The disease may
      get worse to the point that you are no longer able to receive other treatments. There are
      also risks from the additional tests that may be performed, such as biopsies and blood draws.
      You and your doctor will discuss these possible risks, and you will be asked to decide if you
      want to continue receiving the study drug(s).

      End-of-Treatment and Follow-up Visits:

      At about 30 days after your last study drug dose:

        -  You will have a physical exam.

        -  Blood (about 1 tablespoon) will be collected for routine tests, thyroid function tests,
           and liver function tests.

        -  If you are able to become pregnant, blood (about ½ teaspoon) or urine will be collected
           for a pregnancy test.

      At about 70 days after your last study drug dose:

        -  You will have a physical exam.

        -  Blood (about 1 tablespoon) will be collected for routine tests, thyroid function tests,
           and liver function tests.

        -  If you are able to become pregnant, blood (about ½ teaspoon) or urine will be collected
           for a pregnancy test.

      You will also be called every 3 months up to 1½ years and asked about your health. Each call
      should last about 10-15 minutes.

      If you stopped taking the study drug for reasons other than the disease getting worse, you
      will continue to have MRI/CT scans every 8 weeks. If the disease appears to get worse, or you
      start a new anticancer therapy, these scans will stop.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Response Rate (ORR) of Utomilumab Combined With ISA 101b in Patients With Incurable Human Papillomavirus - Positive (HPV+) Oropharyngeal Squamous Cell Carcinoma (OPSCC)
time frame: 9 weeks from start of treatment
description: Overall Response Rate assessed by RECIST 1.1 Criteria
measure: Adverse Events of Utomilumab Combined With ISA 101b in Patients With Incurable Human Papillomavirus - Positive (HPV+) Oropharyngeal Squamous Cell Carcinoma (OPSCC)
time frame: Baseline, and continuously throughout the study at the beginning of each subsequent cycle up to 2 years
description: Adverse events assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for grades 1-3.
measure: Response Rate by irRC of Utomilumab Combined With ISA 101b in Patients With Incurable Human Papillomavirus - Positive (HPV+) Oropharyngeal Squamous Cell Carcinoma (OPSCC)
time frame: Every-8-week schedule beginning from the first on-study assessment on Week 9 up to 2 years
description: Response rate monitored by radiographic assessment.
measure: Progression Free Survival (PFS) of Utomilumab Combined With ISA 101b in Patients With Incurable Human Papillomavirus - Positive (HPV+) Oropharyngeal Squamous Cell Carcinoma (OPSCC)
time frame: Every-8-week schedule beginning from the first on-study assessment on Week 9 up to 2 years
description: PFS defined as the time from first day of treatment to the date of the first documented tumor progression (per RECIST 1.1), or death due to any cause.
arm group label: Utomilumab + ISA101b
arm group type: Experimental
description: Utomilumab by vein every 4 weeks for up to 12 doses beginning on Cycle 1 Day 1.
ISA101b as an injection under the skin every 4 weeks for 3 doses. Participants receive 2 injections each time.
intervention type: Drug
intervention name: Utomilumab
description: Utomilumab given by vein on Cycle 1 Day 1. Cycle 1-2 100 mg, Cycle 3-12 50 mg until progressive disease, toxicity, or 1 yr.
arm group label: Utomilumab + ISA101b
other name: PF-05082566
other name: Anti-CD137
intervention type: Biological
intervention name: ISA101b
description: ISA101b 100 mcg/peptide given subcutaneously every 4 weeks x 3 doses beginning cycle 1 day 1.
arm group label: Utomilumab + ISA101b
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Bonnie S. Glisson, BS,MD
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
facility: 
country: United States
url: http://www.mdanderson.org
description: University of Texas MD Anderson Cancer Center Website
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Oropharyngeal Neoplasms
mesh term: Lip Neoplasms
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 