<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/NCT04470024</url>
  </required_header>
  <id_info>
    <org_study_id>2020000480</org_study_id>
    <nct_id>NCT04470024</nct_id>
  </id_info>
  <brief_title>Phase Ib Trial of Multivalent Autophagosome Vaccine With or Without GITR Agonist, With Anti-PD-1 Immunotherapy in HNSCC</brief_title>
  <official_title>A Phase Ib Study of Multivalent Autophagosome Vaccine, With or Without GITR Agonist, With Sequenced Checkpoint Inhibition (Anti-PD-1) - Immunotherapy Trio in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Providence Health &amp; Services</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Providence Health &amp; Services</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>
      This is a phase Ib study with a safety lead-in (n = 6 per arm) evaluating combinatorial&#xD;
      DPV-001 + sequenced PD-1 blockade, with or without GITR agonist, in recurrent or metastatic&#xD;
      HNSCC.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a phase Ib trial of an autophagosome vaccine (DPV-001) with or without anti-GITR&#xD;
      (INCAGN01876), combined with subsequent anti-PD1 (INCMGA00012), in patients with recurrent or&#xD;
      metastatic HNSCC. Eligible patients will be registered and assigned to one of two treatment&#xD;
      arms. Subjects in Arm 1 will receive combination therapy with DPV-001 with delayed anti-PD-1,&#xD;
      and subjects in Arm 2 will receive DPV-001 and anti-GITR with delayed anti-PD-1 (triplet&#xD;
      therapy). Mandatory biopsy will occur at week 2. Initial restaging CT and mandatory biopsy&#xD;
      will occur at 8 weeks, followed by confirmatory CT at 12 weeks. Subsequent restaging CT will&#xD;
      be performed at week 24 and every 12 weeks thereafter. Starting at week 22, dosing of DPV-101&#xD;
      will switch to a q4wk schedule, while the schedule of anti-GITR and anti-PD1 will remain&#xD;
      unchanged.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 5, 2021</start_date>
  <completion_date type="Anticipated">July 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>The trial will have a run-in safety phase for each of the 2 arms, starting with arm 1 using a standard 3+3 design. If arm 1 is deemed safe, the safety run-in for arm 2 will begin enrollment, using the same 3+3 design. If arm 2 is deemed safe, enrollment will continue to 15 in each arm (total n = 30). Patients enrolling after the safety run-in will be randomly assigned to either arm 1 or arm 2.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adverse Events Assessment</measure>
    <time_frame>from time of informed consent through 90 days after the last study treatment</time_frame>
    <description>frequency, duration, and severity of adverse events</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>ORR, DOR, DCR</measure>
    <time_frame>week 12, 24, and every 12 weeks thereafter</time_frame>
    <description>Determined by investigator assessment per RECIST v1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>1 year, 2 years, and study completion</time_frame>
    <description>Determined from the start of combination until death due to any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of disease control</measure>
    <time_frame>week 12, 24, and every 12 weeks thereafter</time_frame>
    <description>Measured from first report of SD or better (per RECIST v1.1) until PD or death</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">56</enrollment>
  <condition>Cancer of the Head and Neck</condition>
  <arm_group>
    <arm_group_label>Arm 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Vax + delayed anti-PD-1</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Vax + anti-GITR + delayed anti-PD-1</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>INCAGN01876</intervention_name>
    <description>agonistic antihuman GITR mAb</description>
    <arm_group_label>Arm 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>INCMGA00012</intervention_name>
    <description>humanized, hinge-stabilized, IgG4κ mAb that recognized human PD-1</description>
    <arm_group_label>Arm 1</arm_group_label>
    <arm_group_label>Arm 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>DPV-001</intervention_name>
    <description>autophagosome cancer vaccine</description>
    <arm_group_label>Arm 1</arm_group_label>
    <arm_group_label>Arm 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC)&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 (Appendix C)&#xD;
&#xD;
          -  Age 18 years or above.&#xD;
&#xD;
          -  Laboratory values:&#xD;
&#xD;
          -  WBC ≥2000/uL&#xD;
&#xD;
          -  Hgb &gt;8.0 g/dl (patients may be transfused to reach this level)&#xD;
&#xD;
          -  Platelets &gt;75,000 cells/mm3&#xD;
&#xD;
          -  Serum creatinine clearance ≥ 50 mL/min measured or calculated by Cockcroft-Gault (C-G)&#xD;
             equation&#xD;
&#xD;
          -  Negative bHCG (urine/serum) Women of childbearing potential only&#xD;
&#xD;
          -  AST (SGOT) and ALT (SGPT) ≤2.5 × upper limit of laboratory normal (ULN) OR ≤ 5 × ULN&#xD;
             for participants with liver metastases&#xD;
&#xD;
          -  Alkaline phosphatase ≤2.5 × ULN OR ≤ 5 × ULN for participants with liver metastases&#xD;
&#xD;
          -  Total bilirubin ≤1.5 × ULN. If total bilirubin is &gt;1.5, conjugated bilirubin must be ≤&#xD;
             ULN (conjugated bilirubin only needs to be tested if total bilirubin exceeds ULN). If&#xD;
             there is no institutional ULN, then conjugated bilirubin must be &lt; 40% of total&#xD;
             bilirubin.&#xD;
&#xD;
          -  Patients positive for hepatitis B core antibody (anti-HBc, total), are eligible only&#xD;
             if HBV DNA is non-detectable by qPCR.&#xD;
&#xD;
          -  Patients positive for hepatitis C virus (HCV) antibody are eligible only if HCV RNA is&#xD;
             non-detectable by qPCR.&#xD;
&#xD;
          -  Patients positive for HIV 1/2 antibodies, are eligible if ARV treatment compliant with&#xD;
             documented stable CD4 &gt; 300 for at least 6 months and undetectable viral load&#xD;
&#xD;
          -  Ability to give informed consent and comply with the protocol.&#xD;
&#xD;
          -  Anticipated lifespan greater than 12 weeks.&#xD;
&#xD;
          -  Women of childbearing potential must have negative serum/urine pregnancy test &lt;5 days&#xD;
             prior to start of study.&#xD;
&#xD;
          -  Males and women of childbearing potential, must agree to take appropriate precautions&#xD;
             to avoid pregnancy during treatment and through 180 days after last dose of study&#xD;
             treatment (see Appendix A).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Concurrent enrollment in another clinical study, unless it is an observational&#xD;
             (non-interventional) clinical study or during the follow-up period of an&#xD;
             interventional study.&#xD;
&#xD;
          -  Receipt of any investigational anticancer therapy during the last 28 days or 5&#xD;
             half-lives, whichever is shorter, prior to the first dose of study treatment.&#xD;
&#xD;
          -  Any concurrent chemotherapy, investigational agent, biologic, or hormonal therapy for&#xD;
             cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions&#xD;
             (e.g., hormone replacement therapy) is acceptable.&#xD;
&#xD;
          -  Local treatment of isolated lesions for palliative intent is acceptable (e.g., local&#xD;
             surgery or radiotherapy), excluding target lesions, Palliative radiation therapy&#xD;
             cannot be administered less than 1 week prior to the first dose of study treatment.&#xD;
&#xD;
          -  Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of&#xD;
             radiation within 4 weeks of the first dose of study drug.&#xD;
&#xD;
          -  Radiation therapy in the thoracic region that is &gt; 30 Gy within 6 months of the first&#xD;
             dose of study treatment. Note: Participants must have recovered from all&#xD;
             radiation-related toxicities, not require corticosteroids for this purpose, and not&#xD;
             have had radiation pneumonitis.&#xD;
&#xD;
          -  Major surgical procedure (as defined by the Investigator) within 28 days prior to the&#xD;
             first dose of study treatment. Note: Local surgery of isolated lesions for palliative&#xD;
             intent is acceptable.&#xD;
&#xD;
          -  History of organ transplant, including allogeneic stem cell transplantation.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness as deemed by the investigator, including but not&#xD;
             limited to, ongoing or active infection, symptomatic congestive heart failure,&#xD;
             uncontrolled hypertension, unstable angina pectoris, unstable cardiac arrhythmia,&#xD;
             interstitial lung disease or history of, serious chronic gastrointestinal conditions&#xD;
             associated with diarrhea, active noninfectious pneumonitis, or psychiatric&#xD;
             illness/social situations that would limit compliance with study requirement,&#xD;
             substantially increase risk of incurring AEs or compromise the ability of the patient&#xD;
             to give written informed consent.&#xD;
&#xD;
          -  History of another primary malignancy except for:&#xD;
&#xD;
               -  Malignancy treated with curative intent and with no known active disease ≥1.5&#xD;
                  years before the first dose of investigational product and of low potential risk&#xD;
                  for recurrence&#xD;
&#xD;
               -  Adequately treated non-melanoma skin cancer or lentigo maligna without evidence&#xD;
                  of disease&#xD;
&#xD;
               -  Adequately treated carcinoma in situ without evidence of disease&#xD;
&#xD;
          -  History of leptomeningeal carcinomatosis&#xD;
&#xD;
          -  Has untreated central nervous system (CNS) metastases and/or carcinomatous meningitis.&#xD;
             Patients whose brain metastases have been treated may participate provided they show&#xD;
             radiographic stability (imaging at least four weeks apart showing no evidence of&#xD;
             intracranial progression). In addition, any neurologic symptoms that developed either&#xD;
             as a result of the brain metastases or their treatment must have resolved or be stable&#xD;
             either, without the use of steroids, or are stable on a steroid dose of ≤10mg/day of&#xD;
             prednisone or its equivalent and anti-seizure medications for at least 14 days prior&#xD;
             to the start of treatment. Patients on a stable dose of seizure medicines for epilepsy&#xD;
             unrelated to cancer are eligible for the trial.&#xD;
&#xD;
          -  History of active primary immunodeficiency.&#xD;
&#xD;
          -  Active tuberculosis infection (clinical evaluation that includes clinical history,&#xD;
             physical examination and radiographic findings, and TB testing in line with local&#xD;
             practice).&#xD;
&#xD;
          -  Active autoimmune disease requiring systemic immunosuppression in excess of&#xD;
             physiologic maintenance doses of corticosteroids (&gt; 10 mg/day of prednisone or&#xD;
             equivalent).:&#xD;
&#xD;
               -  Physiologic corticosteroid replacement therapy at doses &gt; 10 mg/day of prednisone&#xD;
                  or equivalent for adrenal or pituitary insufficiency and in the absence of active&#xD;
                  autoimmune disease is permitted.&#xD;
&#xD;
               -  Participants with asthma that requires intermittent use of bronchodilators,&#xD;
                  inhaled steroids, or local steroid injections may participate.&#xD;
&#xD;
               -  Participants using topical, ocular, intra-articular, or intranasal steroids (with&#xD;
                  minimal systemic absorption) may participate.&#xD;
&#xD;
               -  Brief courses of corticosteroids for prophylaxis (eg, contrast dye allergy) or&#xD;
                  study treatment-related standard premedication are permitted.&#xD;
&#xD;
          -  Receipt of live attenuated vaccine within 28 days prior to the first dose of study&#xD;
             treatment. Note: patients should not receive live vaccine during study treatment and&#xD;
             up to 30 days after the last dose of study treatment.&#xD;
&#xD;
          -  Known allergy or hypersensitivity to study drug(s) or compounds of similar biologic&#xD;
             composition to the study drug(s), or any of the study drug excipients.&#xD;
&#xD;
          -  Any unresolved NCI CTCAE Grade ≥2 toxicities from prior anti-cancer therapy with the&#xD;
             exception of vitiligo, alopecia, and the laboratory values defined in the inclusion&#xD;
             criteria.&#xD;
&#xD;
          -  Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after&#xD;
             consultation with the Principal Investigator or one of the Co-Principal Investigators.&#xD;
&#xD;
          -  Patients with irreversible toxicity not reasonably expected to be exacerbated by study&#xD;
             treatment may be included only after consultation with the Principal Investigator or&#xD;
             one of the Co-Principal Investigators.&#xD;
&#xD;
          -  Immune-related toxicity during prior checkpoint inhibitor therapy for which permanent&#xD;
             discontinuation of therapy is recommended (per product label or consensus guidelines)&#xD;
             OR&#xD;
&#xD;
          -  any immune-related toxicity requiring intensive or prolonged immunosuppression to&#xD;
             manage (with the exception of endocrinopathy that is well controlled on replacement&#xD;
             hormones).&#xD;
&#xD;
          -  Receipt of systemic antibiotics ≤ 7 days prior to the first dose of study drug.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Portland Providence Medical Center</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>July 9, 2020</study_first_submitted>
  <study_first_submitted_qc>July 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 14, 2020</study_first_posted>
  <last_update_submitted>July 28, 2023</last_update_submitted>
  <last_update_submitted_qc>July 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Head and Neck Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT04470024
org study id: 2020000480
nct id: NCT04470024
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a phase Ib study with a safety lead-in (n = 6 per arm) evaluating combinatorial
      DPV-001 + sequenced PD-1 blockade, with or without GITR agonist, in recurrent or metastatic
      HNSCC.
This is a phase Ib trial of an autophagosome vaccine (DPV-001) with or without anti-GITR
      (INCAGN01876), combined with subsequent anti-PD1 (INCMGA00012), in patients with recurrent or
      metastatic HNSCC. Eligible patients will be registered and assigned to one of two treatment
      arms. Subjects in Arm 1 will receive combination therapy with DPV-001 with delayed anti-PD-1,
      and subjects in Arm 2 will receive DPV-001 and anti-GITR with delayed anti-PD-1 (triplet
      therapy). Mandatory biopsy will occur at week 2. Initial restaging CT and mandatory biopsy
      will occur at 8 weeks, followed by confirmatory CT at 12 weeks. Subsequent restaging CT will
      be performed at week 24 and every 12 weeks thereafter. Starting at week 22, dosing of DPV-101
      will switch to a q4wk schedule, while the schedule of anti-GITR and anti-PD1 will remain
      unchanged.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: The trial will have a run-in safety phase for each of the 2 arms, starting with arm 1 using a standard 3+3 design. If arm 1 is deemed safe, the safety run-in for arm 2 will begin enrollment, using the same 3+3 design. If arm 2 is deemed safe, enrollment will continue to 15 in each arm (total n = 30). Patients enrolling after the safety run-in will be randomly assigned to either arm 1 or arm 2.
primary purpose: Treatment
masking: None (Open Label)
measure: Adverse Events Assessment
time frame: from time of informed consent through 90 days after the last study treatment
description: frequency, duration, and severity of adverse events
measure: ORR, DOR, DCR
time frame: week 12, 24, and every 12 weeks thereafter
description: Determined by investigator assessment per RECIST v1.1
measure: Overall survival (OS)
time frame: 1 year, 2 years, and study completion
description: Determined from the start of combination until death due to any cause
measure: Duration of disease control
time frame: week 12, 24, and every 12 weeks thereafter
description: Measured from first report of SD or better (per RECIST v1.1) until PD or death
arm group label: Arm 1
arm group type: Experimental
description: Vax + delayed anti-PD-1
arm group label: Arm 2
arm group type: Experimental
description: Vax + anti-GITR + delayed anti-PD-1
intervention type: Drug
intervention name: INCAGN01876
description: agonistic antihuman GITR mAb
arm group label: Arm 2
intervention type: Drug
intervention name: INCMGA00012
description: humanized, hinge-stabilized, IgG4κ mAb that recognized human PD-1
arm group label: Arm 1
arm group label: Arm 2
intervention type: Biological
intervention name: DPV-001
description: autophagosome cancer vaccine
arm group label: Arm 1
arm group label: Arm 2
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
responsible party type: Sponsor
mesh term: Head and Neck Neoplasms
sharing ipd: No