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/NCT06026800</url>
    </required_header>
    <id_info>
      <org_study_id>SRRSH2023-755-02</org_study_id>
      <nct_id>NCT06026800</nct_id>
    </id_info>
    <brief_title>Clinical Study of Personalized mRNA Vaccine Encoding Neoantigen in Combination With Standard First-line Treatment in Subjects With Advanced Digestive System Neoplasms</brief_title>
    <official_title>A Clinical Study to Assess the Safety, Feasibility, and Efficacy of Personalized mRNA Vaccine Encoding Neoantigen in Combination With Standard First-line Treatment in Subjects With Advanced Digestive System Neoplasms</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Sir Run Run Shaw Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Hangzhou Neoantigen Therapeutics Co., Ltd.</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Sir Run Run Shaw Hospital</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The purpose of this study is to assess the safety, feasibility, and efficacy of personalized&#xD;
        mRNA vaccine iNeo-Vac-R01 in combination with first-line treatment in subjects with advanced&#xD;
        digestive system neoplasms.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a single-center, open-label, single-arm clinical study of personalized mRNA vaccine&#xD;
        iNeo-Vac-R01 in combination with first-line treatment in subjects with advanced digestive&#xD;
        system neoplasms.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">September 8, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2027</completion_date>
    <primary_completion_date type="Anticipated">August 31, 2027</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>Number of Participants with Adverse Events (AEs) [safety and tolerability]</measure>
      <time_frame>21 days after last iNeo-Vac-R01 dose</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Overall Survival (OS)</measure>
      <time_frame>3 years after first dose of iNeo-Vac-R01</time_frame>
      <description>OS is defined as time between the date of the first dose of iNeo-Vac-R01 and the date of death due to any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Objective Response Rate (ORR)</measure>
      <time_frame>3 years after first dose of iNeo-Vac-R01</time_frame>
      <description>ORR is defined as proportion of subjects with complete response (CR) and partial response (PR) to all subjects based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease Control Rate (DCR)</measure>
      <time_frame>3 years after first dose of iNeo-Vac-R01</time_frame>
      <description>DCR is defined as proportion of subjects with reduced or stable neoplasms that have been maintained for a certain period of time, including the proportion of subjects with CR, PR, and stable disease (SD).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of Response (DOR)</measure>
      <time_frame>3 years after first dose of iNeo-Vac-R01</time_frame>
      <description>DOR is defined as time from first PR or CR until either disease progression or death (whichever is sooner).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression Free Survival (PFS)</measure>
      <time_frame>3 years after first dose of iNeo-Vac-R01</time_frame>
      <description>PFS is defined as time between the date of first dose of iNeo-Vac-R01 and the date of either disease progression or death (whichever is sooner).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Neoantigen-specific T Cell Response [immunogenicity]</measure>
      <time_frame>12 months after first dose of iNeo-Vac-R01</time_frame>
      <description>Detect the level of specific TNF-γ in peripheral blood of subjects by ELISpot in order to measure the neoantigen-specific T cell response of subjects.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>T Cell Subsets [immunogenicity]</measure>
      <time_frame>12 months after first dose of iNeo-Vac-R01</time_frame>
      <description>Detect the proportion of different T cell subsets in T cells by flow cytometry.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cytokines Level [immunogenicity]</measure>
      <time_frame>6 months after first dose of iNeo-Vac-R01</time_frame>
      <description>Record the changes of IL-2, IL-6, IL-8, IL-10, IL-12, and TNF-α in peripheral blood before and after treatment.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">20</enrollment>
    <condition>Digestive System Neoplasms</condition>
    <arm_group>
      <arm_group_label>Personalized mRNA Vaccine iNeo-Vac-R01 with standard first-line treatment</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Subjects will receive at least 4 cycles of standard first-line treatment according to Chinese Society of Clinical Oncology (CSCO) clinical guidelines. Then subjects will receive iNeo-Vac-R01 via IH injection on Day 1 of each 21-day cycle for up to 9 cycles at an applicable dose, identified during the dose escalation phase of the study.</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>iNeo-Vac-R01</intervention_name>
      <description>Personalized mRNA vaccine encoding neoantigen, IH injection</description>
      <arm_group_label>Personalized mRNA Vaccine iNeo-Vac-R01 with standard first-line treatment</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Male or female, &gt;/= 18 years old and &lt;/= 75 years old, with the ability to understand&#xD;
               and provide signed and witnessed informed consent, and agree and are able to comply&#xD;
               with protocol requirements.&#xD;
  &#xD;
            2. Subjects must have one of the histologically- or cytologically-confirmed advanced&#xD;
               (locally advanced or metastatic) digestive system neoplasms, have measurable disease&#xD;
               at study entry defined by RECIST v1.1. Subjects must receive at least 4 cycles of&#xD;
               standard first-line treatment according to CSCO clinical guidelines. The toxic effects&#xD;
               of previous anti-tumor treatments have returned to &lt;/= grade 1 defined by NCI-CTCAE&#xD;
               v5.0 or to the level specified by the inclusion/exclusion criteria.&#xD;
  &#xD;
            3. Expected survival &gt;/= 6 months.&#xD;
  &#xD;
            4. ECOG performance status score of 0 ~ 1.&#xD;
  &#xD;
            5. Sufficient tumor tissue samples can be obtained from subjects for genetic analysis,&#xD;
               with at least 2 puncture tissues with a tumor purity of ≥ 50% required for puncture&#xD;
               samples and at least 0.5cm of tissue required for surgical samples. Alternatively, the&#xD;
               original gene sequencing data required for tumor neoantigen analysis can be provided,&#xD;
               including full exon sequencing data of tumor tissue, transcriptome sequencing data,&#xD;
               and full exon sequencing data of peripheral blood.&#xD;
  &#xD;
            6. Echocardiographic evaluation: left ventricular ejection fraction (LVEF) &gt;/= 50%.&#xD;
  &#xD;
            7. The organ function level must meet the following requirements: absolute neutrophil&#xD;
               count (ANC) &gt;/= 1.5 × 10^9/L, platelet count (PLT) &gt;/= 80 × 10^9/L, hemoglobin (Hb)&#xD;
               &gt;/= 90 g/L; serum total bilirubin (TBIL) &lt;/= 1.5 × ULN, aspartate aminotransferase&#xD;
               (AST) and alanine aminotransferase (ALT) &lt;/= 2.5 × ULN (if there is liver metastasis,&#xD;
               TBIL &lt;/= 3 × ULN, AST, ALT &lt;/= 5 ×ULN are allowed), serum albumin &gt;/= 28g/L, serum&#xD;
               creatinine &lt;/= 1.5 × BUN, Glomerular filtration rate &gt;/= 50mL/min, prothrombin time&#xD;
               (PT) and activated partial thromboplastin time (APTT) and international standardized&#xD;
               ratio (INR) &lt;/= 1.5 × ULN (without anticoagulant therapy) .&#xD;
  &#xD;
            8. For women of childbearing potential: having a negative serum or urine pregnancy test&#xD;
               within 7 days prior to study initiation, agreement to remain abstinent or use&#xD;
               contraceptive measures during the treatment period.&#xD;
  &#xD;
            9. For men: agreement to remain abstinent or use contraceptive measures during the&#xD;
               treatment period.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Subjects with cancer requiring anti-tumor treatment within the 5 years prior to&#xD;
               enrollment in the study (except stage I prostate cancer, cervical cancer in situ,&#xD;
               breast cancer in situ, papillary thyroid cancer and non-melanoma skin cancer that have&#xD;
               been treated).&#xD;
  &#xD;
            2. Subjects who received major surgery, or had obvious traumatic injury or long-term&#xD;
               untreated wounds or fractures within 2 weeks prior to the first dose of iNeo-Vac-R01.&#xD;
  &#xD;
            3. Subjects whose sequencing data was found that there are no new antigens available for&#xD;
               individualized immunotherapy after analysis.&#xD;
  &#xD;
            4. Subjects who prepare to undergo or have previously received bone marrow&#xD;
               transplantation, allogeneic organ transplantation, or allogeneic hematopoietic stem&#xD;
               cell transplantation. Subjects who receive other anti-tumor treatments within 2 weeks&#xD;
               prior to the first dose of iNeo-Vac-R01, including surgical treatment, chemotherapy,&#xD;
               radiation therapy, targeted therapy, endocrine therapy, immunotherapy, biological&#xD;
               therapy, interventional therapy, or other clinical trial related treatments.&#xD;
  &#xD;
            5. Subjects who need to use immunosuppressants, or systemic or absorbable local&#xD;
               glucocorticoids therapy to achieve immunosuppressive effects and continue to use them&#xD;
               within 7 days before the first administration (excluding those with daily doses of&#xD;
               glucocorticoids less than 10mg of prednisone or doses of other therapeutic&#xD;
               glucocorticoids equal to 10mg of prednisone).&#xD;
  &#xD;
            6. Subjects with symptomatic or untreated central nervous system metastases, except those&#xD;
               underwent complete resection and/or radiotherapy and proven to be stable or improved&#xD;
               (confirmed to be stable or improved for at least 4 weeks before the first dose of&#xD;
               iNeo-Vac-R01 by CT or MRI, with no evidence of brain edema and no need for&#xD;
               glucocorticoids or anticonvulsants.&#xD;
  &#xD;
            7. Subjects who received other vaccines within 4 weeks before the first dose of&#xD;
               iNeo-Vac-R01, and are expected to receive other vaccines during treatment period of&#xD;
               the study or within 60 days after the last dose of iNeo-Vac-R01.&#xD;
  &#xD;
            8. Subjects who have an active infection or uncontrollable infection requiring systemic&#xD;
               treatment, including fungi, bacteria, viruses, or other infections; subjects with&#xD;
               active tuberculosis;&#xD;
  &#xD;
            9. Subjects with positive hepatitis B surface antigen (HBsAg) and/or positive hepatitis B&#xD;
               core antibody (HBcAb) and positive hepatitis B virus DNA titer detection greater than&#xD;
               normal range; positive hepatitis C virus (HCV) antibody and HCV RNA detection greater&#xD;
               than normal range; positive human immunodeficiency virus antibody; positive treponema&#xD;
               pallidum-specific antibody.&#xD;
  &#xD;
           10. Subjects with autoimmune diseases or immune deficiencies treated with&#xD;
               immunosuppressive drugs, except vitiligo, type 1 diabetes, autoimmune hypothyroidism&#xD;
               requiring hormone treatment and psoriasis not requiring systemic treatment; known&#xD;
               history of primary immunodeficiency.&#xD;
  &#xD;
           11. Subjects with cardiocerebrovascular events: previously or currently heart valve&#xD;
               disease &gt;/= grade 3, heart failure within 8 weeks before the first dose of&#xD;
               iNeo-Vac-R01 (New York Heart Association [NYHA] cardiac function &gt;/= grade II,&#xD;
               myocardial infarction, unstable angina, stroke, transient ischemic attack, cardiac&#xD;
               surgery (including coronary artery bypass grafting or percutaneous coronary&#xD;
               intervention) within 8 weeks before the first dose of iNeo-Vac-R01, concomitant severe&#xD;
               electrocardiogram abnormalities (such as ventricular flutter, ventricular&#xD;
               fibrillation, multiform ventricular tachycardia, sick sinus syndrome, third degree&#xD;
               atrioventricular block without pacemaker treatment, QTc &gt;/= 480ms, and other&#xD;
               conditions evaluated by the investigators as severe abnormalities), hypertension with&#xD;
               poor drug control (systolic blood pressure &gt;/= 160mmHg and/or diastolic blood pressure&#xD;
               &gt;/= 100mmHg), or other cardiocerebrovascular diseases that have been evaluated by the&#xD;
               investigators as unsuitable for participation in this trial.&#xD;
  &#xD;
           12. Subjects with respiratory disease: previously or currently pulmonary fibrosis,&#xD;
               interstitial lung disease, pneumoconiosis, radiation pneumonia, drug-related&#xD;
               pneumonia, severe asthma, pulmonary hypertension or severe impairment of lung&#xD;
               function, etc.&#xD;
  &#xD;
           13. Subjects with moderate to severe ascites with clinical symptoms; uncontrolled or&#xD;
               moderate to equal amounts of pleural effusion and pericardial effusion.&#xD;
  &#xD;
           14. Subjects with drug abuse; clinical or psychological or social factors that affect&#xD;
               informed consent or research implementation.&#xD;
  &#xD;
           15. Subjects with a history of allergies to immunotherapy or vaccines, or other potential&#xD;
               immunotherapy allergies identified by the investigators.&#xD;
  &#xD;
           16. Subjects identified that it is not suitable for enrollment or may not be able to&#xD;
               complete this experiment for other reasons by the investigators.&#xD;
  &#xD;
           17. Vulnerable groups, including individuals with mental illness, cognitive impairment,&#xD;
               critical patients, minors, pregnant or lactating women, etc.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Xiujun Cai, MD</last_name>
      <phone>0086-0571-86006605</phone>
      <email>caixiujunzju@yahoo.com.cn</email>
    </overall_contact>
    <location>
      <facility>
        <name>Department of General Surgery, Institute of Minimally Invasive Surgery, Sir Run Run Shaw Hospital</name>
        <address>
          <city>Hangzhou</city>
          <state>Zhejiang</state>
          <zip>310000</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Xiujun Cai, MD</last_name>
        <phone>0086-0571-86006605</phone>
        <email>caixiujunzju@yahoo.com.cn</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 25, 2023</study_first_submitted>
    <study_first_submitted_qc>August 30, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 7, 2023</study_first_posted>
    <last_update_submitted>September 8, 2023</last_update_submitted>
    <last_update_submitted_qc>September 8, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 11, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Sir Run Run Shaw Hospital</investigator_affiliation>
      <investigator_full_name>Xiujun Cai</investigator_full_name>
      <investigator_title>The director of Sir Run Run Shaw Hospital</investigator_title>
    </responsible_party>
    <keyword>iNeo-Vac-R01</keyword>
    <keyword>Personalized mRNA Vaccine</keyword>
    <keyword>Neoantigen</keyword>
    <keyword>Digestive System Neoplasms</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Neoplasms</mesh_term>
      <mesh_term>Digestive System Neoplasms</mesh_term>
      <mesh_term>Gastrointestinal Neoplasms</mesh_term>
    </condition_browse>
    <!-- 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/NCT06026800
  org study id: SRRSH2023-755-02
  nct id: NCT06026800
  lead sponsor: 
  collaborator: 
  is fda regulated drug: No
  is fda regulated device: No
  The purpose of this study is to assess the safety, feasibility, and efficacy of personalized
        mRNA vaccine iNeo-Vac-R01 in combination with first-line treatment in subjects with advanced
        digestive system neoplasms.
  This is a single-center, open-label, single-arm clinical study of personalized mRNA vaccine
        iNeo-Vac-R01 in combination with first-line treatment in subjects with advanced digestive
        system neoplasms.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Number of Participants with Adverse Events (AEs) [safety and tolerability]
  time frame: 21 days after last iNeo-Vac-R01 dose
  measure: Overall Survival (OS)
  time frame: 3 years after first dose of iNeo-Vac-R01
  description: OS is defined as time between the date of the first dose of iNeo-Vac-R01 and the date of death due to any cause.
  measure: Objective Response Rate (ORR)
  time frame: 3 years after first dose of iNeo-Vac-R01
  description: ORR is defined as proportion of subjects with complete response (CR) and partial response (PR) to all subjects based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
  measure: Disease Control Rate (DCR)
  time frame: 3 years after first dose of iNeo-Vac-R01
  description: DCR is defined as proportion of subjects with reduced or stable neoplasms that have been maintained for a certain period of time, including the proportion of subjects with CR, PR, and stable disease (SD).
  measure: Duration of Response (DOR)
  time frame: 3 years after first dose of iNeo-Vac-R01
  description: DOR is defined as time from first PR or CR until either disease progression or death (whichever is sooner).
  measure: Progression Free Survival (PFS)
  time frame: 3 years after first dose of iNeo-Vac-R01
  description: PFS is defined as time between the date of first dose of iNeo-Vac-R01 and the date of either disease progression or death (whichever is sooner).
  measure: Neoantigen-specific T Cell Response [immunogenicity]
  time frame: 12 months after first dose of iNeo-Vac-R01
  description: Detect the level of specific TNF-γ in peripheral blood of subjects by ELISpot in order to measure the neoantigen-specific T cell response of subjects.
  measure: T Cell Subsets [immunogenicity]
  time frame: 12 months after first dose of iNeo-Vac-R01
  description: Detect the proportion of different T cell subsets in T cells by flow cytometry.
  measure: Cytokines Level [immunogenicity]
  time frame: 6 months after first dose of iNeo-Vac-R01
  description: Record the changes of IL-2, IL-6, IL-8, IL-10, IL-12, and TNF-α in peripheral blood before and after treatment.
  arm group label: Personalized mRNA Vaccine iNeo-Vac-R01 with standard first-line treatment
  arm group type: Experimental
  description: Subjects will receive at least 4 cycles of standard first-line treatment according to Chinese Society of Clinical Oncology (CSCO) clinical guidelines. Then subjects will receive iNeo-Vac-R01 via IH injection on Day 1 of each 21-day cycle for up to 9 cycles at an applicable dose, identified during the dose escalation phase of the study.
  intervention type: Biological
  intervention name: iNeo-Vac-R01
  description: Personalized mRNA vaccine encoding neoantigen, IH injection
  arm group label: Personalized mRNA Vaccine iNeo-Vac-R01 with standard first-line treatment
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Xiujun Cai, MD
  phone: 0086-0571-86006605
  email: caixiujunzju@yahoo.com.cn
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Sir Run Run Shaw Hospital
  investigator full name: Xiujun Cai
  investigator title: The director of Sir Run Run Shaw Hospital
  mesh term: Neoplasms
  mesh term: Digestive System Neoplasms
  mesh term: Gastrointestinal Neoplasms