xml: <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/NCT06014086</url>
    </required_header>
    <id_info>
      <org_study_id>PHIO-762-2301</org_study_id>
      <nct_id>NCT06014086</nct_id>
    </id_info>
    <brief_title>Intratumoral PH-762 for Cutaneous Carcinoma</brief_title>
    <official_title>Dose Escalation Study of Neoadjuvant Intratumoral PH-762 for Cutaneous Squamous Cell Carcinoma, Melanoma, or Merkel Cell Carcinoma</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Phio Pharmaceuticals Inc.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Phio Pharmaceuticals Inc.</source>
    <oversight_info>
      <has_dmc>Yes</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 trial is to evaluate the safety and tolerability of intratumoral&#xD;
        injections of PH-762 in squamous cell carcinoma, melanoma, or Merkel cell carcinomas of the&#xD;
        skin, to understand what the body does to the PH-762, and to observe how the tumor responds&#xD;
        to the drug. Participants will receive four injections of PH-762 at weekly intervals, into a&#xD;
        single tumor, followed by surgical removal of the tumor approximately two weeks later.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        PH-762 is a potent RNAi molecule targeting PD-1. PH-762 can inhibit the immune checkpoint&#xD;
        PD-1 in the tumor and thereby impede tumor growth. As a preoperative therapy, it may decrease&#xD;
        the lesion size and has the potential to improve surgical morbidity. Intratumoral&#xD;
        immunotherapy aims to use the tumor as a 'self-vaccine'. The local immune stimulation can&#xD;
        induce robust priming of an anti-tumor immune response while generating systemic (abscopal)&#xD;
        tumor responses, mediated by properly activated anti-tumor immune cells in the circulation.&#xD;
        Local delivery of immunotherapy is expected to minimize systemic exposure and off-target&#xD;
        toxicities.&#xD;
  &#xD;
        This is a non-comparative study of neoadjuvant monotherapy using PD-1 targeting&#xD;
        self-delivering RNAi (PH-762) in adult subjects with cutaneous squamous cell carcinoma,&#xD;
        melanoma, or Merkel cell carcinoma. The study treatment consists of four intratumoral&#xD;
        injections of PH-762 at weekly intervals, into a single tumor lesion. Excision of the tumor&#xD;
        will occur approximately two weeks following the fourth dose of IT PH-762, and the subjects&#xD;
        will be followed for an additional 11 weeks.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">September 2025</completion_date>
    <primary_completion_date type="Anticipated">June 2025</primary_completion_date>
    <phase>Phase 1</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>Adverse Events</measure>
      <time_frame>16 weeks</time_frame>
      <description>Incidence, severity, seriousness and relatedness of all treatment-emergent adverse events.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics: maximum plasma concentration (Cmax)</measure>
      <time_frame>3.5 weeks</time_frame>
      <description>Maximum concentration of PH-762 following intratumoral injection.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics: time to maximum plasma concentration (Tmax)</measure>
      <time_frame>3.5 weeks</time_frame>
      <description>Time to maximum concentration of PH-762 following intratumoral injection.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics: area under the curve to last quantifiable plasma concentration (AUClast)</measure>
      <time_frame>3.5 weeks</time_frame>
      <description>Exposure to PH-762 through last quantifiable concentration following intratumoral injection.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pathologic response.</measure>
      <time_frame>5 weeks</time_frame>
      <description>Pathological response will be assessed by relative amount of viable tumor in resection specimens of the treated lesion.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Tumor burden.</measure>
      <time_frame>5 weeks</time_frame>
      <description>Change in tumor burden will be assessed per RECIST/ iRECIST guidelines for the treated lesion.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">30</enrollment>
    <condition>Squamous Cell Carcinoma of the Skin</condition>
    <condition>Malignant Melanoma of Skin</condition>
    <condition>Merkel Cell Carcinoma of Skin</condition>
    <arm_group>
      <arm_group_label>Sequential escalating doses of PH-762.</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Escalating doses of PH-762 are to be tested, with an observation period between doses.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>PH-762</intervention_name>
      <description>PH-762 is a potent RNAi molecule targeting PD-1.</description>
      <arm_group_label>Sequential escalating doses of PH-762.</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Key Inclusion Criteria:&#xD;
  &#xD;
            -  Histologically confirmed cutaneous squamous cell carcinoma (cSCC), melanoma, or Merkel&#xD;
               cell carcinoma, meeting one of the following criteria:&#xD;
  &#xD;
                 -  cSCC, resectable local tumors: must be Stage II or lower, amenable to curative&#xD;
                    resection and in a location where acceptable surgical margins are anticipated&#xD;
  &#xD;
                 -  cSCC, unresectable local tumors: must be Stage II or lower, tumor has been&#xD;
                    unresponsive to prior radiation therapy or is not a candidate for curative&#xD;
                    radiation therapy&#xD;
  &#xD;
                 -  cSCC, metastatic disease: disease has progressed during or following prior&#xD;
                    checkpoint inhibitor therapy (anti-PD-1 or anti-PD-L1 antibody)&#xD;
  &#xD;
                 -  Melanoma, metastatic disease: Stage IV disease with a cutaneous lesion that has&#xD;
                    progressed during or following checkpoint inhibitor therapy (anti-PD-1/-PD-L1),&#xD;
                    and if BRAF-mutation is present, has progressed during or following prior&#xD;
                    treatment with anti-BRAF + MEK therapy&#xD;
  &#xD;
                 -  Merkel cell carcinoma, metastatic disease: Stage IV disease with a cutaneous&#xD;
                    lesion that has progressed during or following checkpoint inhibitor therapy&#xD;
                    (anti-PD-1/PD-L1)&#xD;
  &#xD;
            -  A minimum of one tumor of ≥ 1.0 cm and &lt; 3.0 cm in longest dimension that is&#xD;
               accessible (with or without imaging guidance) for intratumoral injection and for&#xD;
               biopsy and surgical excision must be present. The tumor is not necrotic, hemorrhagic,&#xD;
               or friable, and is not within 2 cm of the eye or within 0.5 cm of or on the lip&#xD;
               (including the vermilion border) and is not in a mucosal or visceral location.&#xD;
  &#xD;
          Key Exclusion Criteria:&#xD;
  &#xD;
            -  Other malignancy within prior 3 years, with certain exceptions.&#xD;
  &#xD;
            -  Current cancer chemotherapy, radiation therapy, immunotherapy, or biologic therapy.&#xD;
  &#xD;
            -  Any serious or uncontrolled medical disorder including auto-immune disease that may&#xD;
               increase the risk associated with study participation or study drug administration, or&#xD;
               interfere with the interpretation of study results.&#xD;
  &#xD;
            -  Females who are pregnant or are breastfeeding.&#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>L Mahoney</last_name>
      <role>Study Director</role>
      <affiliation>Phio Pharmaceuticals Inc.</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>L Mahoney</last_name>
      <phone>(508) 929-3601</phone>
      <email>lmahoney@phiopharma.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>M Spellman, MD</last_name>
      <phone>(508) 929-3601</phone>
      <email>mspellman@phiopharma.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Phio Pharmaceuticals Corp.</name>
        <address>
          <city>Marlborough</city>
          <state>Massachusetts</state>
          <zip>01752</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>L Mahoney</last_name>
        <email>lmahoney@phiopharma.com</email>
      </contact>
      <contact_backup>
        <last_name>M Spellman, MD</last_name>
        <email>mspellman@phiopharma.com</email>
      </contact_backup>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 22, 2023</study_first_submitted>
    <study_first_submitted_qc>August 25, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 28, 2023</study_first_posted>
    <last_update_submitted>August 25, 2023</last_update_submitted>
    <last_update_submitted_qc>August 25, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 28, 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>Carcinoma, Merkel Cell</mesh_term>
      <mesh_term>Carcinoma</mesh_term>
      <mesh_term>Melanoma</mesh_term>
      <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06014086
  org study id: PHIO-762-2301
  nct id: NCT06014086
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  The goal of this clinical trial is to evaluate the safety and tolerability of intratumoral
        injections of PH-762 in squamous cell carcinoma, melanoma, or Merkel cell carcinomas of the
        skin, to understand what the body does to the PH-762, and to observe how the tumor responds
        to the drug. Participants will receive four injections of PH-762 at weekly intervals, into a
        single tumor, followed by surgical removal of the tumor approximately two weeks later.
  PH-762 is a potent RNAi molecule targeting PD-1. PH-762 can inhibit the immune checkpoint
        PD-1 in the tumor and thereby impede tumor growth. As a preoperative therapy, it may decrease
        the lesion size and has the potential to improve surgical morbidity. Intratumoral
        immunotherapy aims to use the tumor as a 'self-vaccine'. The local immune stimulation can
        induce robust priming of an anti-tumor immune response while generating systemic (abscopal)
        tumor responses, mediated by properly activated anti-tumor immune cells in the circulation.
        Local delivery of immunotherapy is expected to minimize systemic exposure and off-target
        toxicities.
  
        This is a non-comparative study of neoadjuvant monotherapy using PD-1 targeting
        self-delivering RNAi (PH-762) in adult subjects with cutaneous squamous cell carcinoma,
        melanoma, or Merkel cell carcinoma. The study treatment consists of four intratumoral
        injections of PH-762 at weekly intervals, into a single tumor lesion. Excision of the tumor
        will occur approximately two weeks following the fourth dose of IT PH-762, and the subjects
        will be followed for an additional 11 weeks.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Adverse Events
  time frame: 16 weeks
  description: Incidence, severity, seriousness and relatedness of all treatment-emergent adverse events.
  measure: Pharmacokinetics: maximum plasma concentration (Cmax)
  time frame: 3.5 weeks
  description: Maximum concentration of PH-762 following intratumoral injection.
  measure: Pharmacokinetics: time to maximum plasma concentration (Tmax)
  time frame: 3.5 weeks
  description: Time to maximum concentration of PH-762 following intratumoral injection.
  measure: Pharmacokinetics: area under the curve to last quantifiable plasma concentration (AUClast)
  time frame: 3.5 weeks
  description: Exposure to PH-762 through last quantifiable concentration following intratumoral injection.
  measure: Pathologic response.
  time frame: 5 weeks
  description: Pathological response will be assessed by relative amount of viable tumor in resection specimens of the treated lesion.
  measure: Tumor burden.
  time frame: 5 weeks
  description: Change in tumor burden will be assessed per RECIST/ iRECIST guidelines for the treated lesion.
  arm group label: Sequential escalating doses of PH-762.
  arm group type: Experimental
  description: Escalating doses of PH-762 are to be tested, with an observation period between doses.
  intervention type: Drug
  intervention name: PH-762
  description: PH-762 is a potent RNAi molecule targeting PD-1.
  arm group label: Sequential escalating doses of PH-762.
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: L Mahoney
  role: Study Director
  affiliation: Phio Pharmaceuticals Inc.
  last name: L Mahoney
  phone: (508) 929-3601
  email: lmahoney@phiopharma.com
  last name: M Spellman, MD
  phone: (508) 929-3601
  email: mspellman@phiopharma.com
  facility: 
  contact: 
  contact backup: 
  country: United States
  responsible party type: Sponsor
  mesh term: Carcinoma, Merkel Cell
  mesh term: Carcinoma
  mesh term: Melanoma
  mesh term: Carcinoma, Squamous Cell
  sharing ipd: No