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/NCT05978102</url>
    </required_header>
    <id_info>
      <org_study_id>K2023091</org_study_id>
      <nct_id>NCT05978102</nct_id>
    </id_info>
    <brief_title>A Dose Escalation and Dose Expansion Clinical Study of STI-7349 in Subjects With Advanced Solid Tumors</brief_title>
    <official_title>An Open-label, Dose Escalation and Dose Expansion Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of STI-7349 in Subjects With Advanced Solid Tumors</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>The Fourth Affiliated Hospital of Zhejiang University School of Medicine</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>The Fourth Affiliated Hospital of Zhejiang University School of Medicine</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>
        This is a first-in-human, Phase Ⅰ, open-label, 2-period dose escalation and expansion study&#xD;
        of STI-7349 administered intravenously to subjects with advanced solid tumors:&#xD;
  &#xD;
          -  Period I is divided into two parts: Dose escalation for STI-7349 alone (1A) and dose&#xD;
             expansion for STI-7349 alone (1B). In Part 1A, a rapid titration approach and&#xD;
             traditional 3 + 3 trial design will be used to assess the safety, dose-limiting&#xD;
             toxicities (DLTs), maximum tolerated dose (MTD), PK/biomarker profile, and to determine&#xD;
             the recommended Phase 2 dose (RP2D) of STI-7349 alone; in Part 1B, an expansion study of&#xD;
             STI-7349 alone will be conducted in target tumor types that may potentially benefit to&#xD;
             assess the safety and preliminary efficacy of STI-7349 alone.&#xD;
  &#xD;
          -  Period Ⅱ is divided into two parts: Dose escalation for STI-7349 in combination with&#xD;
             Pembrolizumab (2A) and dose expansion for STI-7349 in combination with Pembrolizumab&#xD;
             (2B). In Part 2A, a dose escalation study of STI-7349 in combination with Pembrolizumab&#xD;
             is planned to be conducted using ½ RP2D of STI-7349 alone as the starting dose, which&#xD;
             will use a traditional 3 + 3 trial design to assess the safety, DLTs, MTD, PK/biomarker&#xD;
             profile of STI-7349 in combination with Pembrolizumab, and to determine the RP2D of&#xD;
             STI-7349 in combination with Pembrolizumab; in Part 2B, an expansion study of STI-7349&#xD;
             in combination with Pembrolizumab will be conducted in target tumor types that may&#xD;
             potentially benefit to assess the safety and preliminary efficacy of the combination.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Period I: Dose escalation of STI-7349 alone (1A) According to preclinical test data, 1 mg is&#xD;
        the preliminary dose and an accelerated titration test design is used. The subsequent&#xD;
        starting dose is designed to be 3 mg, with 100%, 100%, 50%, and 33.3% dose escalation in&#xD;
        reference to the modified Fibonacci method, and the six dose groups initially set for&#xD;
        STI-7349 dose escalation are 1 mg, 3 mg, 6 mg, 12 mg, 18 mg, and 24 mg, respectively, if no&#xD;
        adverse events specified in the accelerated titration method below occurred. Subjects who&#xD;
        pass screening will be sequentially enrolled into 6 dose groups from low to high dose in&#xD;
        order.&#xD;
  &#xD;
        Subjects in all dose groups will receive 21 days per dosing cycle and Day 1 of each cycle&#xD;
        will be the dosing day.&#xD;
  &#xD;
        Part 1A of this trial will use rapid titration and a traditional 3 + 3 trial design.&#xD;
  &#xD;
        Period I: Dose expansion of STI-7349 alone (1B) Based on data from the 1A escalation period,&#xD;
        target tumor types with potential benefit are selected, and subjects are expanded to 20 to 30&#xD;
        at the RP2D of STI-7349 alone to conduct an expansion study of STI-7349 alone to further&#xD;
        assess the safety and preliminary efficacy of the RP2D of STI-7349 alone. STI-7349 will be&#xD;
        administered at the same frequency as that in Part 1A and continued until the maximum 2-year&#xD;
        dosing period, disease progression/relapse, death, intolerable toxicity, inability of the&#xD;
        subject to benefit from study treatment as judged by the investigator, withdrawal from&#xD;
        clinical study treatment by the subject or his/her legal representative, loss to follow-up,&#xD;
        or completion of the entire study, whichever comes first.&#xD;
  &#xD;
        Period II: Dose escalation for STI-7349 in combination with Pembrolizumab (2A) A dose&#xD;
        escalation study of STI-7349 in combination with Pembrolizumab is conducted in subjects with&#xD;
        advanced solid tumors according to the RP2D of STI-7349 alone determined in Period I. ½ RP2D&#xD;
        of STI-7349 alone is used as the starting dose for the dose escalation study of the&#xD;
        combination, and since the expected RP2D dose is 24 mg, the starting dose for the combination&#xD;
        is 12 mg. The approved standard therapeutic dose of Pembrolizumab is 200 mg IV. According to&#xD;
        the results of Period I of the study, the three dose groups for the preliminary&#xD;
        dose-escalation study of STI-7349 in combination with Pembrolizumab are 12 mg, 18 mg, and 24&#xD;
        mg. Subjects who pass screening will be sequentially enrolled into 3 dose groups from low to&#xD;
        high dose in order.&#xD;
  &#xD;
        Period II: Dose expansion for STI-7349 in combination with Pembrolizumab (2B) According to&#xD;
        the data from the 2A escalation period, target tumor types with potential benefit are&#xD;
        selected, and subjects are expanded to 20 to 30 at the RP2D of the combination to conduct a&#xD;
        dose expansion study of STI-7349 in combination with Pembrolizumab to further assess the&#xD;
        safety and preliminary efficacy of the RP2D of the combination. STI-7349 will be administered&#xD;
        at the same frequency as that in Part 2A and continued until the maximum 2-year dosing&#xD;
        period, disease progression/relapse, death, intolerable toxicity, inability of the subject to&#xD;
        benefit from study treatment as judged by the investigator, withdrawal from clinical study&#xD;
        treatment by the subject or his/her legal representative, loss to follow-up, or completion of&#xD;
        the entire study, whichever comes first.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 2023</start_date>
    <completion_date type="Anticipated">December 2025</completion_date>
    <primary_completion_date type="Anticipated">December 2025</primary_completion_date>
    <phase>Phase 1/Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Number of participants of STI-7349 alone with treatment-related adverse events as assessed by CTCAE v5.0.</measure>
      <time_frame>Up to 2 years.</time_frame>
      <description>Assessing the incidence of adverse events (AEs) of STI-7349 alone using the Common Terminology Criteria for Adverse Events (CTCAE Version 5.0)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of participants of STI-7349 in combination with Pembrolizumab with treatment-related adverse events as assessed by CTCAE v5.0.</measure>
      <time_frame>Up to 2 years.</time_frame>
      <description>Assessing the incidence of adverse events (AEs) of STI-7349 in combination with Pembrolizumab using the Common Terminology Criteria for Adverse Events (CTCAE Version 5.0)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>To assess the AUC(Area under the concentration-time curve) of cationic lipids of STl-7349 alone in the treatment of advanced solid tumors</measure>
      <time_frame>The first four cycles(each cycle is 21 days).</time_frame>
      <description>To assess the pharmacokinetics(PK) of cationic lipids of STl-7349 alone by collecting serum at protocol-specified time points:AUC.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the Tmax(Time to peak) of cationic lipids of STl-7349 alone in the treatment of advanced solid tumors.</measure>
      <time_frame>The first four cycles(each cycle is 21 days).</time_frame>
      <description>To assess the PK of cationic lipids of STl-7349 alone by collecting serum at protocol-specified time points:Tmax.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the Cmax(Peak concentration) of cationic lipids of STl-7349 alone in the treatment of advanced solid tumors.</measure>
      <time_frame>The first four cycles(each cycle is 21 days).</time_frame>
      <description>To assess the PK of cationic lipids of STl-7349 alone by collecting serum at protocol-specified time points:Cmax.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the AUC of mRNA(messenger-ribonucleic acid) of STl-7349 alone in the treatment of advanced solid tumors.</measure>
      <time_frame>The first four cycles(each cycle is 21 days).</time_frame>
      <description>To assess the PK of mRNA of STl-7349 alone by collecting serum at protocol-specified time points:AUC.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the Tmax of mRNA of STl-7349 alone in the treatment of advanced solid tumors.</measure>
      <time_frame>The first four cycles(each cycle is 21 days).</time_frame>
      <description>To assess the PK of mRNA of STl-7349 alone by collecting serum at protocol-specified time points:Tmax.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the Cmax of mRNA of STI-7349 alone in the treatment of advanced solid tumors.</measure>
      <time_frame>The first four cycles(each cycle is 21 days).</time_frame>
      <description>To assess the PK of mRNA of STl-7349 alone by collecting serum at protocol-specified time points:Cmax.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the AUC of HSA-IL2v protein(Human serum albumin interleukin 2 fusion protein) of STl-7349 alone in the treatment of advanced solid tumors.</measure>
      <time_frame>The first four cycles(each cycle is 21 days).</time_frame>
      <description>To assess the PK of HSA-IL2v protein of STl-7349 alone by collecting serum at protocol-specified time points:AUC.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the Tmax of HSA-IL2v protein of STI-7349 alone in the treatment of advanced solid tumors</measure>
      <time_frame>The first four cycles(each cycle is 21 days).</time_frame>
      <description>To assess the PK of HSA-IL2v protein of STl-7349 alone by collecting serum at protocol-specified time points:Tmax.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the Cmax of HSA-IL2v protein of STI-7349 alone in the treatment of advanced solid tumors.</measure>
      <time_frame>The first four cycles(each cycle is 21 days).</time_frame>
      <description>To assess the PK of HSA-IL2v protein of STl-7349 alone by collecting serum at protocol-specified time points:Cmax.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the AUC of cationic lipids of STI-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors</measure>
      <time_frame>The first four cycles(each cycle is 21 days).</time_frame>
      <description>To assess the PK of cationic lipids of STI-7349 in combination with Pembrolizumab by collecting serum at protocol-specified time points:AUC.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the Tmax of cationic lipids of STI-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors</measure>
      <time_frame>The first four cycles(each cycle is 21 days).</time_frame>
      <description>To assess the PK of cationic lipids of STI-7349 in combination with Pembrolizumab by collecting serum at protocol-specified time points:Tmax.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the Cmax of cationic lipids of STI-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors</measure>
      <time_frame>The first four cycles(each cycle is 21 days).</time_frame>
      <description>To assess the PK of cationic lipids of STI-7349 in combination with Pembrolizumab by collecting serum at protocol-specified time points:Cmax.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the AUC of mRNA of STI-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors</measure>
      <time_frame>The first four cycles(each cycle is 21 days).</time_frame>
      <description>To assess the PK of mRNA of STI-7349 in combination with Pembrolizumab by collecting serum at protocol-specified time points:AUC.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the Tmax of mRNA of ST1-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors</measure>
      <time_frame>The first four cycles(each cycle is 21 days).</time_frame>
      <description>To assess the PK of mRNA of STI-7349 in combination with Pembrolizumab by collecting serum at protocol-specified time points:Tmax.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the Cmax of mRNA of STI-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors</measure>
      <time_frame>The first four cycles(each cycle is 21 days).</time_frame>
      <description>To assess the PK of mRNA of STI-7349 in combination with Pembrolizumab by collecting serum at protocol-specified time points:Cmax.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the AUC of HSA-IL2v protein of STI-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors</measure>
      <time_frame>The first four cycles(each cycle is 21 days).</time_frame>
      <description>To assess the PK of HSA-IL2v protein of STI-7349 in combination with Pembrolizumab by collecting serum at protocol-specified time points:AUC.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the Tmax of HSA-IL2v protein of STI-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors</measure>
      <time_frame>The first four cycles(each cycle is 21 days).</time_frame>
      <description>To assess the PK of HSA-IL2v protein of STI-7349 in combination with Pembrolizumab by collecting serum at protocol-specified time points:Tmax.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the Cmax of HSA-IL2v protein of STI-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors</measure>
      <time_frame>The first four cycles(each cycle is 21 days).</time_frame>
      <description>To assess the PK of HSA-IL2v protein of STI-7349 in combination with Pembrolizumab by collecting serum at protocol-specified time points:Cmax.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the AUC of Pembrolizumab of STl-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors</measure>
      <time_frame>The first four cycles(each cycle is 21 days).</time_frame>
      <description>To assess the PK of Pembrolizumab of STI-7349 in combination with Pembrolizumab by collecting serum at protocol-specified time points:AUC.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the Tmax of Pembrolizumab of STl-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors</measure>
      <time_frame>The first four cycles(each cycle is 21 days).</time_frame>
      <description>To assess the PK of Pembrolizumab of STI-7349 in combination with Pembrolizumab by collecting serum at protocol-specified time points:Tmax.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the Cmax of Pembrolizumab of STl-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors</measure>
      <time_frame>The first four cycles(each cycle is 21 days).</time_frame>
      <description>To assess the PK of Pembrolizumab of STI-7349 in combination with Pembrolizumab by collecting serum at protocol-specified time points:Cmax.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the ORR(Objective response rate) of STl-7349 alone in the treatment of advanced solid tumors</measure>
      <time_frame>Through study completion, an average of 2 years.</time_frame>
      <description>Defined as the proportion of subjects with CR(Complete Response)+PR(Partial Response) for the best response assessed according to the RECIST 1.1 criteria.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the DCR(Disease control rate) of STI-7349 alone in the treatment of advanced solid tumors</measure>
      <time_frame>Through study completion, an average of 2 years.</time_frame>
      <description>Defined as the proportion of subjects whose best response was CR+PR+SD(Stable Disease) as assessed according to RECIST 1.1 criteria.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the DOR(Duration of response) of STl-7349 alone in the treatment of advanced solid tumors</measure>
      <time_frame>Through study completion, an average of 2 years.</time_frame>
      <description>Defined as the time between the first onset of CR or PR and the onset of PD(Progressive Disease) or death from any cause (whichever occurs first).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the PFS(Progression-free survival) of STl-7349 alone in the treatment of advanced solid tumors</measure>
      <time_frame>Through study completion, an average of 2 years.</time_frame>
      <description>Defined as the time between the subject's initial study treatment and the onset of PD or death from any cause, whichever occurs first.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the OS(Overall survival)of STl-7349 alone in the treatment of advanced solid tumors</measure>
      <time_frame>Through study completion, an average of 2 years.</time_frame>
      <description>Defined as the time between a subject's initial study treatment and death from any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the the ORR of STl-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors</measure>
      <time_frame>Through study completion, an average of 2 years.</time_frame>
      <description>Defined as the proportion of subjects with CR+PR for the best response assessed according to the RECIST 1.1 criteria.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the DCR of STl-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors</measure>
      <time_frame>Through study completion, an average of 2 years.</time_frame>
      <description>Defined as the proportion of subjects whose best response was CR+PR+SD as assessed according to RECIST 1.1 criteria.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the DOR of STl-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors</measure>
      <time_frame>Through study completion, an average of 2 years.</time_frame>
      <description>Defined as the time between the first onset of CR or PR and the onset of PD or death from any cause (whichever occurs first).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the PFS of STI-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors</measure>
      <time_frame>Through study completion, an average of 2 years.</time_frame>
      <description>Defined as the time between the subject's initial study treatment and the onset of PD or death from any cause, whichever occurs first.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the OS of STI-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors</measure>
      <time_frame>Through study completion, an average of 2 years.</time_frame>
      <description>Defined as the time between a subject's initial study treatment and death from any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the anti-PEG(polyethylene glycol) ADA(immunogenicity) of STI-7349 alone in the treatment of advanced solid tumor.</measure>
      <time_frame>Through study completion, an average of 2 years.</time_frame>
      <description>Change from baseline in anti-PEG ADA contents measured in plasma and correlation with PK/PD(pharmacodynamics).ADA blood sample collection time point:Within 1 week before injection, each cycle before administration(each cycle is 21 days) and at EOT(End-of-treatment visit).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the anti-HSA-IL2v ADA content of STI-7349 alone in the treatment of advanced solid tumors</measure>
      <time_frame>Through study completion, an average of 2 years.</time_frame>
      <description>Change from baseline in anti-HSA-IL2v ADA contents measured in plasma and correlation with PK/PD.ADA blood sample collection time point:Within 1 week before injection, each cycle before administration(each cycle is 21 days) and at EOT.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the anti-PEG ADA of STI-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors</measure>
      <time_frame>Through study completion, an average of 2 years.</time_frame>
      <description>Change from baseline in anti-PEG ADA contents measured in plasma and correlation with PK/PD.ADA blood sample collection time point:Within 1 week before injection, each cycle before administration(each cycle is 21 days) and at EOT.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the anti-HSA-IL2v ADA of STI-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors</measure>
      <time_frame>Through study completion, an average of 2 years.</time_frame>
      <description>Change from baseline in anti-HSA-IL2v ADA contents measured in plasma and correlation with PK/PD.ADA blood sample collection time point:Within 1 week before injection, each cycle before administration(each cycle is 21 days) and at EOT.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the anti-Pembrolizumab Nab of STI-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors</measure>
      <time_frame>Through study completion, an average of 2 years.</time_frame>
      <description>Change from baseline in anti-Pembrolizumab Nab contents measured in plasma and correlation with PK/PD.ADA blood sample collection time point:Within 1 week before injection, each cycle before administration(each cycle is 21 days) and at EOT.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">124</enrollment>
    <condition>Advanced Solid Tumor</condition>
    <arm_group>
      <arm_group_label>STI-7349 alone</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Dose escalation and dose expansion for STI-7349 alone,to determine the RP2D and to evaluate the preliminary antitumor activity of STI-7349 in specific solid tumor patients.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>STl-7349 in combination with Pembrolizumab</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Dose escalation and dose expansion for STI-7349 in combination with Pembrolizumab,to determine the RP2D of STI-7349 in combination with Pembrolizumab and to evaluate the preliminary antitumor activity in specific solid tumor patients.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>STI-7349</intervention_name>
      <description>Administered by intravenous infusion (IV)</description>
      <arm_group_label>STI-7349 alone</arm_group_label>
      <arm_group_label>STl-7349 in combination with Pembrolizumab</arm_group_label>
      <other_name>IL2v mRNA</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Pembrolizumab</intervention_name>
      <description>Administered by intravenous infusion (IV)</description>
      <arm_group_label>STl-7349 in combination with Pembrolizumab</arm_group_label>
      <other_name>anti-PD-1 monoclonal antibody</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          -&#xD;
  &#xD;
          To be enrolled in this study, subjects must meet all of the following inclusion criteria:&#xD;
  &#xD;
            1. Subjects should have fully understood the study and voluntarily signed an informed&#xD;
               consent form.&#xD;
  &#xD;
            2. Age 18 to 75 years (inclusive).&#xD;
  &#xD;
            3. ECOG(Eastern U.S. Oncology Collaborative Group) score of 0 to 1.&#xD;
  &#xD;
            4. Expected survival ≥ 12 weeks.&#xD;
  &#xD;
            5. According to Response Evaluation Criteria in Solid Tumors (RECIST1.1), the subject has&#xD;
               at least one measurable lesion, that is, the subject has at least one lymph node&#xD;
               lesion (minimum diameter ≥ 1.5 cm) or non-lymph node lesion (maximum diameter ≥ 1 cm)&#xD;
               diagnosed by computed tomography (CT)/magnetic resonance imaging (MRI) examination; if&#xD;
               the lesion that previously received local therapy (radiotherapy, ablation, vascular&#xD;
               intervention, etc.) is the only lesion, there must be a clear imaging basis for&#xD;
               disease progression of this lesion after local therapy.&#xD;
  &#xD;
            6. Subjects with malignant advanced solid tumors confirmed by histopathology or cytology&#xD;
               who have failed standard treatment, or cannot tolerate standard treatment, or cannot&#xD;
               obtain standard treatment for various reasons, or have no standard treatment.&#xD;
  &#xD;
            7. The subject has major organ function meeting the following criteria within 7 days&#xD;
               prior to first dose [The subject had not received blood component transfusion within&#xD;
               14 days prior to testing. Subjects had not received supportive treatment with human&#xD;
               granulocyte colony-stimulating factor (G-CSF), thrombopoietin (TPO), thrombopoietin&#xD;
               receptor agonist, interleukin-11, and erythropoietin (EPO) within 7 days prior to&#xD;
               testing.]:&#xD;
  &#xD;
                 1. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L;&#xD;
  &#xD;
                 2. Platelet (PLT) ≥ 100 × 109/L;&#xD;
  &#xD;
                 3. Hemoglobin (HGB) ≥ 90 g/L;&#xD;
  &#xD;
                 4. Alanine aminotransferase (AST) ≤ 2.5 × ULN (≤ 5 × ULN(Upper limit of normal&#xD;
                    value) if liver involvement is known);&#xD;
  &#xD;
                 5. Aspartate aminotransferase (ALT) ≤ 2.5 × ULN (≤ 5 × ULN if liver involvement is&#xD;
                    known);&#xD;
  &#xD;
                 6. Total bilirubin (TBIL) ≤ 1.5 × ULN (≤ 3.0 × ULN if Gilbert's syndrome is&#xD;
                    diagnosed);&#xD;
  &#xD;
                 7. Serum creatinine ≤ 1.5 × ULN or estimated glomerular filtration rate (eGFR,&#xD;
                    calculated according to the Cockcroft-Gault formula, or by measuring 24-hour&#xD;
                    urine) ≥ 40 mL/min;&#xD;
  &#xD;
                 8. International normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin&#xD;
                    time (APTT) ≤ 1.5 × ULN.&#xD;
  &#xD;
            8. The subject has not recovered to ≤ Grade 1 from toxicity reactions to previous&#xD;
               anti-tumor treatment (except for Grade 2 neurotoxicity and Grade 2 hypothyroidism,&#xD;
               alopecia and pigmentation of any grade caused by anti-tumor treatment, laboratory test&#xD;
               parameters are shown in Inclusion Criterion 8).&#xD;
  &#xD;
            9. Subject is willing and able to comply with the study schedule and all other study&#xD;
               protocol requirements.&#xD;
  &#xD;
           10. Women of childbearing potential (women of non-childbearing potential are defined as&#xD;
               sexually mature women who have undergone hysterectomy or bilateral oophorectomy or&#xD;
               bilateral salpingectomy or bilateral tubal ligation/occlusion, or who are unable to&#xD;
               have children because of congenital or acquired disease, or have natural menopause for&#xD;
               ≥ 12 months) must have a negative blood pregnancy test during screening. Female&#xD;
               subjects of childbearing potential and male subjects must use a highly effective&#xD;
               method of contraception at screening through 6 months after the last treatment.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          -&#xD;
  &#xD;
          To be enrolled in this study, subjects must not meet any of the following exclusion&#xD;
          criteria:&#xD;
  &#xD;
            1. The subject has a known hypersensitivity to any component of the investigational&#xD;
               product or IL-2.&#xD;
  &#xD;
            2. Subjects have participated in any therapeutic clinical study within 28 days prior to&#xD;
               first dose, were enrolled and treated. In addition, subjects are in the survival&#xD;
               follow-up phase of observational or interventional studies.&#xD;
  &#xD;
            3. Subjects have used immunomodulatory drugs within 14 days or 5 half-lives (whichever is&#xD;
               longer) prior to the first dose, including but not limited to thymosin, IL-2, IL-15,&#xD;
               interferon, etc.&#xD;
  &#xD;
            4. The subject has received chimeric antigen receptor T-cell immunotherapy (CAR-T) within&#xD;
               3 months prior to the first dose; the subject has received chemotherapy (at least 6&#xD;
               weeks for chemotherapeutic agents nitrosoureas and mitomycin C, and at least 14 days&#xD;
               for oral fluoropyrimidines), endocrine therapy, targeted therapy (washout period of 14&#xD;
               days or 5 half-lives for small-molecule targeted therapy, whichever is longer),&#xD;
               immunotherapy (for immunomodulatory agents see exclusion criterion 3), tumor&#xD;
               embolization, etc. within 28 days prior to the first dose; the subject has received&#xD;
               radiotherapy within 14 days prior to the first dose, palliative radiotherapy for&#xD;
               symptom control is allowed to be completed at least 7 days prior to the first dose;&#xD;
               the subject has received traditional Chinese medicine for an approved indication of&#xD;
               anti-tumor within 7 days prior to the first dose.&#xD;
  &#xD;
            5. The subject has undergone major surgery within 28 days or minor surgery within 7 days&#xD;
               prior to the first dose, or had an unhealed wound, ulcer, or bone fracture or required&#xD;
               elective surgery during the study (except for diagnostic biopsy, insertion of vascular&#xD;
               access device).&#xD;
  &#xD;
            6. Subjects have received a live attenuated vaccine within 28 days prior to the first&#xD;
               dose or plan to receive it during the study.&#xD;
  &#xD;
            7. Subjects have received systemic immunosuppressants within 28 days prior to first dose&#xD;
               excluding:&#xD;
  &#xD;
                 1. Intranasal inhaled topical steroid therapy or topical steroid injection (eg,&#xD;
                    intra-articular injection);&#xD;
  &#xD;
                 2. Systemic corticosteroid therapy not exceeding 10 mg/day prednisone or its&#xD;
                    physiologic equivalent doses;&#xD;
  &#xD;
                 3. Corticosteroids as prophylaxis for allergic reactions (eg, premedication for CT);&#xD;
  &#xD;
                 4. As prophylaxis for infusion reactions.&#xD;
  &#xD;
            8. The subject had a known history of central nervous system (CNS) involvement, or spinal&#xD;
               cord compression, or carcinomatous meningitis, or leptomeningeal carcinomatosis.&#xD;
  &#xD;
            9. Subjects had uncontrolled third space effusions requiring repeated drainage, such as&#xD;
               pleural effusion, ascites, pericardial effusion, etc. (subjects who do not require&#xD;
               drainage of effusion or have no significant increase in effusion after stopping&#xD;
               drainage for 3 days may be enrolled), or third space effusions that are bloody by&#xD;
               diagnostic puncture.&#xD;
  &#xD;
           10. The subject had another malignancy within 5 years prior to the first dose, except for&#xD;
               radically treated early malignancies (carcinoma in situ or Stage I tumor), such as&#xD;
               adequately treated basal or squamous cell carcinoma of the skin, carcinoma in situ of&#xD;
               the cervix or breast after radical resection, early papillary thyroid carcinoma, or&#xD;
               prostate cancer with local Gleason score ≤ 6.&#xD;
  &#xD;
           11. The subject had active autoimmune or inflammatory diseases, including inflammatory&#xD;
               bowel disease (eg, ulcerative colitis or Crohn's disease), diverticulitis (other than&#xD;
               diverticular disease), celiac disease, systemic lupus erythematosus, Sarcoidosis&#xD;
               syndrome or Wegener' s syndrome (granuloma with polyangiitis), Graves' disease,&#xD;
               rheumatoid arthritis, hypophysitis, uveitis, etc.), or a history of the disease within&#xD;
               the previous 2 years (subject with vitiligo, psoriasis, alopecia, or Graves' disease&#xD;
               not requiring systemic therapy within the last 2 years, hypothyroidism requiring&#xD;
               thyroid hormone replacement therapy only, and Type 1 diabetes mellitus requiring&#xD;
               insulin replacement therapy only may be enrolled).&#xD;
  &#xD;
           12. The subject has active or uncontrolled HBV（Hepatitis B Virus） (HBsAg positive and/or&#xD;
               HBcAb positive and HBV DNA titer positive), HCV (HCV-Ab positive and HCV RNA titer&#xD;
               positive), HIV(Human Immunodeficiency Virus) positive.&#xD;
  &#xD;
           13. The subject had an active bacterial, viral, or fungal infection (defined as a subject&#xD;
               demonstrating persistent signs/symptoms related to infection that do not improve&#xD;
               despite appropriate antibiotic or other therapy) or required intravenous (IV)&#xD;
               antibiotics within 72 hours prior to the first dose.&#xD;
  &#xD;
           14. Severe or uncontrolled cardiovascular or cerebrovascular disease requiring treatment,&#xD;
               including but not limited to:&#xD;
  &#xD;
                 1. New York Heart Association (NYHA) cardiac functional classification &gt; 2;&#xD;
  &#xD;
                 2. Unstable angina not controlled by medication;&#xD;
  &#xD;
                 3. Subject has had a myocardial infarction within 6 months prior to first dose;&#xD;
  &#xD;
                 4. History of myocarditis;&#xD;
  &#xD;
                 5. Cardiac tamponade;&#xD;
  &#xD;
                 6. Poorly controlled arrhythmias (eg, subjects who develop ventricular tachycardia&#xD;
                    during antiarrhythmic drug therapy will be excluded; subjects with first degree&#xD;
                    atrioventricular block or asymptomatic left anterior bundle branch block/right&#xD;
                    bundle branch block will not be excluded);&#xD;
  &#xD;
                 7. 12-lead electrocardiogram QTcF（The QT interval values were corrected for heart&#xD;
                    rate using Fridericia's formula） &gt; 470 msec;&#xD;
  &#xD;
                 8. Left ventricular ejection fraction (LVEF) &lt; 50%;&#xD;
  &#xD;
                 9. Poorly controlled hypertension (On the basis of lifestyle modification, the&#xD;
                    subject has been taking adequate doses of 2 or more antihypertensive agents&#xD;
                    reasonably tolerated for more than 1 month, but blood pressure remains&#xD;
                    substandard. Or subjects have been taking 4 or more antihypertensive drugs for&#xD;
                    effective blood pressure control) or hypotension;&#xD;
  &#xD;
                10. Epilepsy not controlled by medication;&#xD;
  &#xD;
                11. The subject had a stroke, cerebrovascular accident, or transient ischemic attack&#xD;
                    within 6 months prior to first dose.&#xD;
  &#xD;
           15. The subject has known chronic obstructive pulmonary disease (COPD) and forced&#xD;
               expiratory volume in one second (FEV1) &lt; 50% of predicted normal. It should be noted&#xD;
               that subjects suspected of having COPD must have FEV1 testing and must be excluded if&#xD;
               FEV1 is &lt; 50% of predicted normal.&#xD;
  &#xD;
           16. The subject has known moderate or severe persistent asthma, or had a history of asthma&#xD;
               within the past 2 years, or has uncontrolled asthma of any classification currently&#xD;
               (note that subjects with current controllable intermittent asthma or controllable mild&#xD;
               persistent asthma are allowed).&#xD;
  &#xD;
           17. The subject has previous and current pulmonary disease such as interstitial pneumonia&#xD;
               (including drug-induced), pneumoconiosis, pulmonary fibrosis, or severely impaired&#xD;
               pulmonary function; the subject has active pulmonary tuberculosis and is receiving&#xD;
               anti-tuberculosis treatment or has received anti-tuberculosis treatment within 1 year&#xD;
               prior to the first dose.&#xD;
  &#xD;
           18. The subject has experienced clinically significant bleeding symptoms within 3 months&#xD;
               prior to first dose. The subject had evident symptoms of coughing up blood within 28&#xD;
               days prior to the first dose with hemoptysis of half a teaspoon (2.5 mL) or more per&#xD;
               session.&#xD;
  &#xD;
           19. The subject had a history of abdominal fistula, gastrointestinal perforation,&#xD;
               intra-abdominal abscess, or acute gastrointestinal bleeding within 6 months prior to&#xD;
               the first dose.&#xD;
  &#xD;
           20. The subject had a history of deep vein thrombosis, pulmonary embolism, or any other&#xD;
               serious thromboembolism (except thrombosis caused by a vascular access device, or&#xD;
               superficial venous thrombosis) within 3 months prior to the first dose.&#xD;
  &#xD;
           21. The subject has hepatic encephalopathy, or hepatorenal syndrome, or Child-Pugh class B&#xD;
               (&gt; 7 points) or more severe cirrhosis.&#xD;
  &#xD;
           22. The subject had a known history of primary immunodeficiency.&#xD;
  &#xD;
           23. The subject had a known history of allogeneic organ transplantation and allogeneic&#xD;
               hematopoietic stem cell transplantation (except corneal transplantation).&#xD;
  &#xD;
           24. Pregnant or lactating women.&#xD;
  &#xD;
           25. Subject has any active serious psychiatric disorder, medical condition, or other&#xD;
               symptoms/conditions that could affect treatment, compliance, or ability to give&#xD;
               informed consent at the discretion of the investigator.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>June 25, 2023</study_first_submitted>
    <study_first_submitted_qc>August 3, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 7, 2023</study_first_posted>
    <last_update_submitted>August 3, 2023</last_update_submitted>
    <last_update_submitted_qc>August 3, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 7, 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>Neoplasms</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Pembrolizumab</mesh_term>
    </intervention_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/NCT05978102
  org study id: K2023091
  nct id: NCT05978102
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  This is a first-in-human, Phase Ⅰ, open-label, 2-period dose escalation and expansion study
        of STI-7349 administered intravenously to subjects with advanced solid tumors:
  
          -  Period I is divided into two parts: Dose escalation for STI-7349 alone (1A) and dose
             expansion for STI-7349 alone (1B). In Part 1A, a rapid titration approach and
             traditional 3 + 3 trial design will be used to assess the safety, dose-limiting
             toxicities (DLTs), maximum tolerated dose (MTD), PK/biomarker profile, and to determine
             the recommended Phase 2 dose (RP2D) of STI-7349 alone; in Part 1B, an expansion study of
             STI-7349 alone will be conducted in target tumor types that may potentially benefit to
             assess the safety and preliminary efficacy of STI-7349 alone.
  
          -  Period Ⅱ is divided into two parts: Dose escalation for STI-7349 in combination with
             Pembrolizumab (2A) and dose expansion for STI-7349 in combination with Pembrolizumab
             (2B). In Part 2A, a dose escalation study of STI-7349 in combination with Pembrolizumab
             is planned to be conducted using ½ RP2D of STI-7349 alone as the starting dose, which
             will use a traditional 3 + 3 trial design to assess the safety, DLTs, MTD, PK/biomarker
             profile of STI-7349 in combination with Pembrolizumab, and to determine the RP2D of
             STI-7349 in combination with Pembrolizumab; in Part 2B, an expansion study of STI-7349
             in combination with Pembrolizumab will be conducted in target tumor types that may
             potentially benefit to assess the safety and preliminary efficacy of the combination.
  Period I: Dose escalation of STI-7349 alone (1A) According to preclinical test data, 1 mg is
        the preliminary dose and an accelerated titration test design is used. The subsequent
        starting dose is designed to be 3 mg, with 100%, 100%, 50%, and 33.3% dose escalation in
        reference to the modified Fibonacci method, and the six dose groups initially set for
        STI-7349 dose escalation are 1 mg, 3 mg, 6 mg, 12 mg, 18 mg, and 24 mg, respectively, if no
        adverse events specified in the accelerated titration method below occurred. Subjects who
        pass screening will be sequentially enrolled into 6 dose groups from low to high dose in
        order.
  
        Subjects in all dose groups will receive 21 days per dosing cycle and Day 1 of each cycle
        will be the dosing day.
  
        Part 1A of this trial will use rapid titration and a traditional 3 + 3 trial design.
  
        Period I: Dose expansion of STI-7349 alone (1B) Based on data from the 1A escalation period,
        target tumor types with potential benefit are selected, and subjects are expanded to 20 to 30
        at the RP2D of STI-7349 alone to conduct an expansion study of STI-7349 alone to further
        assess the safety and preliminary efficacy of the RP2D of STI-7349 alone. STI-7349 will be
        administered at the same frequency as that in Part 1A and continued until the maximum 2-year
        dosing period, disease progression/relapse, death, intolerable toxicity, inability of the
        subject to benefit from study treatment as judged by the investigator, withdrawal from
        clinical study treatment by the subject or his/her legal representative, loss to follow-up,
        or completion of the entire study, whichever comes first.
  
        Period II: Dose escalation for STI-7349 in combination with Pembrolizumab (2A) A dose
        escalation study of STI-7349 in combination with Pembrolizumab is conducted in subjects with
        advanced solid tumors according to the RP2D of STI-7349 alone determined in Period I. ½ RP2D
        of STI-7349 alone is used as the starting dose for the dose escalation study of the
        combination, and since the expected RP2D dose is 24 mg, the starting dose for the combination
        is 12 mg. The approved standard therapeutic dose of Pembrolizumab is 200 mg IV. According to
        the results of Period I of the study, the three dose groups for the preliminary
        dose-escalation study of STI-7349 in combination with Pembrolizumab are 12 mg, 18 mg, and 24
        mg. Subjects who pass screening will be sequentially enrolled into 3 dose groups from low to
        high dose in order.
  
        Period II: Dose expansion for STI-7349 in combination with Pembrolizumab (2B) According to
        the data from the 2A escalation period, target tumor types with potential benefit are
        selected, and subjects are expanded to 20 to 30 at the RP2D of the combination to conduct a
        dose expansion study of STI-7349 in combination with Pembrolizumab to further assess the
        safety and preliminary efficacy of the RP2D of the combination. STI-7349 will be administered
        at the same frequency as that in Part 2A and continued until the maximum 2-year dosing
        period, disease progression/relapse, death, intolerable toxicity, inability of the subject to
        benefit from study treatment as judged by the investigator, withdrawal from clinical study
        treatment by the subject or his/her legal representative, loss to follow-up, or completion of
        the entire study, whichever comes first.
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Number of participants of STI-7349 alone with treatment-related adverse events as assessed by CTCAE v5.0.
  time frame: Up to 2 years.
  description: Assessing the incidence of adverse events (AEs) of STI-7349 alone using the Common Terminology Criteria for Adverse Events (CTCAE Version 5.0)
  measure: Number of participants of STI-7349 in combination with Pembrolizumab with treatment-related adverse events as assessed by CTCAE v5.0.
  time frame: Up to 2 years.
  description: Assessing the incidence of adverse events (AEs) of STI-7349 in combination with Pembrolizumab using the Common Terminology Criteria for Adverse Events (CTCAE Version 5.0)
  measure: To assess the AUC(Area under the concentration-time curve) of cationic lipids of STl-7349 alone in the treatment of advanced solid tumors
  time frame: The first four cycles(each cycle is 21 days).
  description: To assess the pharmacokinetics(PK) of cationic lipids of STl-7349 alone by collecting serum at protocol-specified time points:AUC.
  measure: To assess the Tmax(Time to peak) of cationic lipids of STl-7349 alone in the treatment of advanced solid tumors.
  time frame: The first four cycles(each cycle is 21 days).
  description: To assess the PK of cationic lipids of STl-7349 alone by collecting serum at protocol-specified time points:Tmax.
  measure: To assess the Cmax(Peak concentration) of cationic lipids of STl-7349 alone in the treatment of advanced solid tumors.
  time frame: The first four cycles(each cycle is 21 days).
  description: To assess the PK of cationic lipids of STl-7349 alone by collecting serum at protocol-specified time points:Cmax.
  measure: To assess the AUC of mRNA(messenger-ribonucleic acid) of STl-7349 alone in the treatment of advanced solid tumors.
  time frame: The first four cycles(each cycle is 21 days).
  description: To assess the PK of mRNA of STl-7349 alone by collecting serum at protocol-specified time points:AUC.
  measure: To assess the Tmax of mRNA of STl-7349 alone in the treatment of advanced solid tumors.
  time frame: The first four cycles(each cycle is 21 days).
  description: To assess the PK of mRNA of STl-7349 alone by collecting serum at protocol-specified time points:Tmax.
  measure: To assess the Cmax of mRNA of STI-7349 alone in the treatment of advanced solid tumors.
  time frame: The first four cycles(each cycle is 21 days).
  description: To assess the PK of mRNA of STl-7349 alone by collecting serum at protocol-specified time points:Cmax.
  measure: To assess the AUC of HSA-IL2v protein(Human serum albumin interleukin 2 fusion protein) of STl-7349 alone in the treatment of advanced solid tumors.
  time frame: The first four cycles(each cycle is 21 days).
  description: To assess the PK of HSA-IL2v protein of STl-7349 alone by collecting serum at protocol-specified time points:AUC.
  measure: To assess the Tmax of HSA-IL2v protein of STI-7349 alone in the treatment of advanced solid tumors
  time frame: The first four cycles(each cycle is 21 days).
  description: To assess the PK of HSA-IL2v protein of STl-7349 alone by collecting serum at protocol-specified time points:Tmax.
  measure: To assess the Cmax of HSA-IL2v protein of STI-7349 alone in the treatment of advanced solid tumors.
  time frame: The first four cycles(each cycle is 21 days).
  description: To assess the PK of HSA-IL2v protein of STl-7349 alone by collecting serum at protocol-specified time points:Cmax.
  measure: To assess the AUC of cationic lipids of STI-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors
  time frame: The first four cycles(each cycle is 21 days).
  description: To assess the PK of cationic lipids of STI-7349 in combination with Pembrolizumab by collecting serum at protocol-specified time points:AUC.
  measure: To assess the Tmax of cationic lipids of STI-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors
  time frame: The first four cycles(each cycle is 21 days).
  description: To assess the PK of cationic lipids of STI-7349 in combination with Pembrolizumab by collecting serum at protocol-specified time points:Tmax.
  measure: To assess the Cmax of cationic lipids of STI-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors
  time frame: The first four cycles(each cycle is 21 days).
  description: To assess the PK of cationic lipids of STI-7349 in combination with Pembrolizumab by collecting serum at protocol-specified time points:Cmax.
  measure: To assess the AUC of mRNA of STI-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors
  time frame: The first four cycles(each cycle is 21 days).
  description: To assess the PK of mRNA of STI-7349 in combination with Pembrolizumab by collecting serum at protocol-specified time points:AUC.
  measure: To assess the Tmax of mRNA of ST1-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors
  time frame: The first four cycles(each cycle is 21 days).
  description: To assess the PK of mRNA of STI-7349 in combination with Pembrolizumab by collecting serum at protocol-specified time points:Tmax.
  measure: To assess the Cmax of mRNA of STI-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors
  time frame: The first four cycles(each cycle is 21 days).
  description: To assess the PK of mRNA of STI-7349 in combination with Pembrolizumab by collecting serum at protocol-specified time points:Cmax.
  measure: To assess the AUC of HSA-IL2v protein of STI-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors
  time frame: The first four cycles(each cycle is 21 days).
  description: To assess the PK of HSA-IL2v protein of STI-7349 in combination with Pembrolizumab by collecting serum at protocol-specified time points:AUC.
  measure: To assess the Tmax of HSA-IL2v protein of STI-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors
  time frame: The first four cycles(each cycle is 21 days).
  description: To assess the PK of HSA-IL2v protein of STI-7349 in combination with Pembrolizumab by collecting serum at protocol-specified time points:Tmax.
  measure: To assess the Cmax of HSA-IL2v protein of STI-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors
  time frame: The first four cycles(each cycle is 21 days).
  description: To assess the PK of HSA-IL2v protein of STI-7349 in combination with Pembrolizumab by collecting serum at protocol-specified time points:Cmax.
  measure: To assess the AUC of Pembrolizumab of STl-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors
  time frame: The first four cycles(each cycle is 21 days).
  description: To assess the PK of Pembrolizumab of STI-7349 in combination with Pembrolizumab by collecting serum at protocol-specified time points:AUC.
  measure: To assess the Tmax of Pembrolizumab of STl-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors
  time frame: The first four cycles(each cycle is 21 days).
  description: To assess the PK of Pembrolizumab of STI-7349 in combination with Pembrolizumab by collecting serum at protocol-specified time points:Tmax.
  measure: To assess the Cmax of Pembrolizumab of STl-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors
  time frame: The first four cycles(each cycle is 21 days).
  description: To assess the PK of Pembrolizumab of STI-7349 in combination with Pembrolizumab by collecting serum at protocol-specified time points:Cmax.
  measure: To assess the ORR(Objective response rate) of STl-7349 alone in the treatment of advanced solid tumors
  time frame: Through study completion, an average of 2 years.
  description: Defined as the proportion of subjects with CR(Complete Response)+PR(Partial Response) for the best response assessed according to the RECIST 1.1 criteria.
  measure: To assess the DCR(Disease control rate) of STI-7349 alone in the treatment of advanced solid tumors
  time frame: Through study completion, an average of 2 years.
  description: Defined as the proportion of subjects whose best response was CR+PR+SD(Stable Disease) as assessed according to RECIST 1.1 criteria.
  measure: To assess the DOR(Duration of response) of STl-7349 alone in the treatment of advanced solid tumors
  time frame: Through study completion, an average of 2 years.
  description: Defined as the time between the first onset of CR or PR and the onset of PD(Progressive Disease) or death from any cause (whichever occurs first).
  measure: To assess the PFS(Progression-free survival) of STl-7349 alone in the treatment of advanced solid tumors
  time frame: Through study completion, an average of 2 years.
  description: Defined as the time between the subject's initial study treatment and the onset of PD or death from any cause, whichever occurs first.
  measure: To assess the OS(Overall survival)of STl-7349 alone in the treatment of advanced solid tumors
  time frame: Through study completion, an average of 2 years.
  description: Defined as the time between a subject's initial study treatment and death from any cause.
  measure: To assess the the ORR of STl-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors
  time frame: Through study completion, an average of 2 years.
  description: Defined as the proportion of subjects with CR+PR for the best response assessed according to the RECIST 1.1 criteria.
  measure: To assess the DCR of STl-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors
  time frame: Through study completion, an average of 2 years.
  description: Defined as the proportion of subjects whose best response was CR+PR+SD as assessed according to RECIST 1.1 criteria.
  measure: To assess the DOR of STl-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors
  time frame: Through study completion, an average of 2 years.
  description: Defined as the time between the first onset of CR or PR and the onset of PD or death from any cause (whichever occurs first).
  measure: To assess the PFS of STI-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors
  time frame: Through study completion, an average of 2 years.
  description: Defined as the time between the subject's initial study treatment and the onset of PD or death from any cause, whichever occurs first.
  measure: To assess the OS of STI-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors
  time frame: Through study completion, an average of 2 years.
  description: Defined as the time between a subject's initial study treatment and death from any cause.
  measure: To assess the anti-PEG(polyethylene glycol) ADA(immunogenicity) of STI-7349 alone in the treatment of advanced solid tumor.
  time frame: Through study completion, an average of 2 years.
  description: Change from baseline in anti-PEG ADA contents measured in plasma and correlation with PK/PD(pharmacodynamics).ADA blood sample collection time point:Within 1 week before injection, each cycle before administration(each cycle is 21 days) and at EOT(End-of-treatment visit).
  measure: To assess the anti-HSA-IL2v ADA content of STI-7349 alone in the treatment of advanced solid tumors
  time frame: Through study completion, an average of 2 years.
  description: Change from baseline in anti-HSA-IL2v ADA contents measured in plasma and correlation with PK/PD.ADA blood sample collection time point:Within 1 week before injection, each cycle before administration(each cycle is 21 days) and at EOT.
  measure: To assess the anti-PEG ADA of STI-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors
  time frame: Through study completion, an average of 2 years.
  description: Change from baseline in anti-PEG ADA contents measured in plasma and correlation with PK/PD.ADA blood sample collection time point:Within 1 week before injection, each cycle before administration(each cycle is 21 days) and at EOT.
  measure: To assess the anti-HSA-IL2v ADA of STI-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors
  time frame: Through study completion, an average of 2 years.
  description: Change from baseline in anti-HSA-IL2v ADA contents measured in plasma and correlation with PK/PD.ADA blood sample collection time point:Within 1 week before injection, each cycle before administration(each cycle is 21 days) and at EOT.
  measure: To assess the anti-Pembrolizumab Nab of STI-7349 in combination with Pembrolizumab in the treatment of advanced solid tumors
  time frame: Through study completion, an average of 2 years.
  description: Change from baseline in anti-Pembrolizumab Nab contents measured in plasma and correlation with PK/PD.ADA blood sample collection time point:Within 1 week before injection, each cycle before administration(each cycle is 21 days) and at EOT.
  arm group label: STI-7349 alone
  arm group type: Experimental
  description: Dose escalation and dose expansion for STI-7349 alone,to determine the RP2D and to evaluate the preliminary antitumor activity of STI-7349 in specific solid tumor patients.
  arm group label: STl-7349 in combination with Pembrolizumab
  arm group type: Experimental
  description: Dose escalation and dose expansion for STI-7349 in combination with Pembrolizumab,to determine the RP2D of STI-7349 in combination with Pembrolizumab and to evaluate the preliminary antitumor activity in specific solid tumor patients.
  intervention type: Drug
  intervention name: STI-7349
  description: Administered by intravenous infusion (IV)
  arm group label: STI-7349 alone
  arm group label: STl-7349 in combination with Pembrolizumab
  other name: IL2v mRNA
  intervention type: Drug
  intervention name: Pembrolizumab
  description: Administered by intravenous infusion (IV)
  arm group label: STl-7349 in combination with Pembrolizumab
  other name: anti-PD-1 monoclonal antibody
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  responsible party type: Sponsor
  mesh term: Neoplasms
  mesh term: Pembrolizumab