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/NCT05989724</url>
    </required_header>
    <id_info>
      <org_study_id>SON-DP-A001-ST</org_study_id>
      <nct_id>NCT05989724</nct_id>
    </id_info>
    <brief_title>A First-in-Human Study of SON-DP in Participants With Relapsed/Refractory Intolerant to Standard of Care Therapies for Advanced/Metastatic Solid Tumors</brief_title>
    <official_title>A First-in-Human (FIH), Open-Label, Phase Ia/Ib Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of SON-DP in Participants With Relapsed/Metastatic Solid Tumors</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Qurgen Inc.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Qurgen 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>
        This proposed Phase I clinical trial of SON-DP is an FIH, open-label, Phase Ia/Ib dose&#xD;
        escalation and expansion study to evaluate the safety, tolerability, PK, and PD of SON-DP in&#xD;
        participants with relapsed/refractory/intolerant to standard of care therapies, for advanced/&#xD;
        metastatic solid tumors.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        -  In an effort to overcome the major challenges of the conventional cancer cell-killing&#xD;
             therapy for high side effect, drug resistance, cancer recurrence and tumor&#xD;
             heterogenicity, Qurgen Inc. is developing a novel transcription factor (TF) protein&#xD;
             anticancer drug, named SON-DP, to treat the Participants with relapsed and advanced&#xD;
             metastatic solid tumors. Proposed as an effective therapeutic drug product for a&#xD;
             cell-converting cancer therapy, SON-DP is expected to transform cancer cells in situ&#xD;
             into normal tissue cells via a SON-DP induced cancer cell reprogramming and&#xD;
             re-differentiation process as an innovative rationale.&#xD;
  &#xD;
          -  SON-DP is developed based on the rationale of cancer cell conversion into normal tissue&#xD;
             cells as the primary mechanism of actions of a new cancer therapy, not by cancer&#xD;
             cell-killing, the traditional goals of chemotherapy, radiation therapy, targeted therapy&#xD;
             and immune therapy. Cancer cell conversion is achieved by the SON-DP induced pluripotent&#xD;
             re-programming in situ inside tumor tissue into transient iPSCs (tiPSCs) that quickly&#xD;
             re-differentiate into normal tissue cells induced by the differentiating resident tissue&#xD;
             environment. The in situ generated tiPSCs either secrete exosomes, providing the&#xD;
             embryonic stem cells (ESC)-like microenvironments to transform the surrounding cancer&#xD;
             cells into normal tissue cells for an overall malignant phenotype reversion (OMPR) (an&#xD;
             effect named as a bystander effect), or display a targeting effect that enables the in&#xD;
             situ generated tiPSCs to track down the distant metastatic cancer cells for OMPR (an&#xD;
             effect named as a tropism effect). The SON-DP-induced cell reprogramming also restored&#xD;
             the mutation-caused and compromised p53 checkpoint in cancer cells to re-establish cell&#xD;
             quality control system that ensures the downstream re-differentiation of the in situ&#xD;
             generated tiPSCs into normal tissue cells. Overall, this SON-DP-induced re-programming&#xD;
             and re-differentiation process is capable of transforming both primary and metastatic&#xD;
             cancer cells into normal tissue cells.&#xD;
  &#xD;
          -  Preclinical studies demonstrated that treatment of tumors with SON-DP resulted in&#xD;
             eradication of late-stage cancers and long term (over 3 years) survival without teratoma&#xD;
             formation and cancer recurrence in multiple tumor-bearing mouse/rat (syngeneic) or human&#xD;
             xenograft rodent models, providing high treatment efficacy of this cell-converting&#xD;
             cancer therapy. Thus, the cell-converting cancer therapy rationale represents a new&#xD;
             cancer therapeutic strategy. SON-DP was tolerated in tumor-bearing rodents, as well as&#xD;
             in naïve rats, dogs, and monkeys as demonstrated by GLP-enabled (rats and dogs) and&#xD;
             non-GLP (monkey) toxicity study and after repeated IV administrations at higher doses&#xD;
             compared with the planned clinical dose range. Therefore, the current nonclinical&#xD;
             studies, including pharmacodynamics (PD), pharmacokinetics (PK) and toxicology studies,&#xD;
             support the safety and efficacy of SON-DP TF protein drug product to be used in clinical&#xD;
             studies of human participants. This first-in-human (FIH) clinical study will be&#xD;
             conducted in selected types of relapsed/refractory advanced/metastatic solid tumors as a&#xD;
             step in demonstrating the utility of this anticancer agent.&#xD;
  &#xD;
          -  In this SON-DP-A001-ST clinical trial, SON-DP is given to the participants with late&#xD;
             stage solid tumors through 90-minutes IV infusion either once a week or twice a week at&#xD;
             first 4 dose levels during the first Phase I dose escalation stage with the purpose to&#xD;
             identify the final schedule (either once a week or twice a week) for the last 3 higher&#xD;
             dose levels and the recommended phase II dose (RP2D) for the second Phase Ib does&#xD;
             expansion stage that will focus on 4 cancer types including breast cancer, pancreatic&#xD;
             cancer, ovarian cancer and colorectal cancer.&#xD;
  &#xD;
          -  During Phase Ia dose escalation stage, an accelerated 3+3 design will be followed. A&#xD;
             Safety Monitoring Committee (SMC) will be formed to evaluate all the safety, efficacy,&#xD;
             pharmacokinetic and pharmacodynamic data of each dose level cohort to decide if the&#xD;
             SON-DP dose level should be either escalated to the next dose level or de-escalated to&#xD;
             one level below or determination of maximum tolerated dose (MTD) or RP2D confirmation or&#xD;
             others. Phase Ia will enroll the participants with various types of solid tumors that&#xD;
             metastasized and not response to standard treatment.&#xD;
  &#xD;
          -  During Phase Ib dose expansion stage, SON-DP will be used, at RP2D dose level, to treat&#xD;
             the participants with 4 specific cancer types including breast cancer, pancreatic&#xD;
             cancer, ovary cancer or colorectal cancer. Four groups of cancer cohorts will be opened&#xD;
             with eligible participants who have relapsed/refractory/intolerant to standard of care&#xD;
             therapies of these four advanced/metastatic solid tumors. Participants will be followed&#xD;
             for safety, confirmation of the RP2D, PK, PD, and anti-tumor activity as measured by&#xD;
             standard assessment tools.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Anticipated">August 2023</start_date>
    <completion_date type="Anticipated">March 2026</completion_date>
    <primary_completion_date type="Anticipated">September 2025</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <intervention_model_description>This is a first-in-human and first-in-class, open-label, Phase I clinical trial including a Phase Ia dose escalation stage for the participants with all solid tumor types using seven dose levels of SON-DP to determine the RP2D, MTD and DLT; and a Phase Ib dose expansion stage for the participants of four arms including breast cancer, pancreatic cancer, ovary cancer or colorectal cancer using the RP2D of SON-DP obtained from Phase Ia.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Number of participants with AEs, with abnormal vital signs, abnormal ECG readings, abnormal clinical laboratory tests results, abnormal physical examinations and abnormal ECOG performance status.</measure>
      <time_frame>Up to 7 months after the first dose</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>MTD (Maximum tolerable dose) / RP2D (Recommended dose for phase II)</measure>
      <time_frame>During 28-day DLT observation period</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>ORR</measure>
      <time_frame>Up to 6 months after the first dose</time_frame>
      <description>Objective response rate (ORR)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>DCR</measure>
      <time_frame>Up to 6 months after the first dose</time_frame>
      <description>Disease control rate (DCR)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>DOR</measure>
      <time_frame>Up to 6 months after the first dose</time_frame>
      <description>Duration of response (DoR)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>TTP</measure>
      <time_frame>Up to 6 months after the first dose</time_frame>
      <description>Time-to-event endpoints of time to disease progression (TTP)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PFS</measure>
      <time_frame>Up to 6 months after the first dose</time_frame>
      <description>Progression-free survival (PFS)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>OS</measure>
      <time_frame>Time Frame: Up to 12 months after the first dose</time_frame>
      <description>Overall Survival (OS)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cmax</measure>
      <time_frame>Up to 6 months after the first dose</time_frame>
      <description>Maximum serum concentration (Cmax) of 3 proteins from SON-DP will be investigated.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Tmax</measure>
      <time_frame>Up to 6 months after the first dose</time_frame>
      <description>Time to maximum serum concentration (Tmax) of 3 proteins from SON-DP will be investigated.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>T1/2</measure>
      <time_frame>Up to 6 months after the first dose</time_frame>
      <description>Half-life (T1/2) of 3 proteins from SON-DP will be investigated.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>AUC0-t</measure>
      <time_frame>Up to 6 months after the first dose</time_frame>
      <description>AUC0-t is defined as area under the serum concentration-time curve from time 0 to the time of the last measurable concentration.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>CL</measure>
      <time_frame>Up to 6 months after the first dose</time_frame>
      <description>Clearance (CL) in the serum of 3 proteins from SON-DP per unit of time will be investigated.</description>
    </secondary_outcome>
    <other_outcome>
      <measure>SON-DP concentration in tumor biopsy tissue</measure>
      <time_frame>Up to 5 weeks after the first dose</time_frame>
    </other_outcome>
    <number_of_arms>15</number_of_arms>
    <enrollment type="Anticipated">150</enrollment>
    <condition>Solid Tumor</condition>
    <condition>Breast Cancer</condition>
    <condition>Pancreatic Cancer</condition>
    <condition>Ovarian Cancer</condition>
    <condition>Colorectal Cancer</condition>
    <arm_group>
      <arm_group_label>Dose escalation, Cohort 1</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Drug: SON-DP&#xD;
  1 participant or 3 participants with solid tumor will be treated with SON-DP by 90-minute IV infusion in the cohort 1 at dose level 1 once per week in 28-day cycle, for up to 6 cycles.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Dose escalation, Cohort 2</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Drug: SON-DP&#xD;
  1 participant or 3 participants with solid tumor will be treated with SON-DP by 90-minute IV infusion in the cohort 2 at dose level 2 once per week in 28-day cycle, for up to 6 cycles.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Dose escalation, Cohort 3</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Drug: SON-DP 3 participants with solid tumor will be treated with SON-DP by 90-minute IV infusion in the cohort 3 at dose level 3 once per week in 28-day cycle, for up to 6 cycles.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Dose escalation, Cohort 4</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Drug: SON-DP 3 participants with solid tumor will be treated with SON-DP by 90-minute IV infusion in the cohort 4 at dose level 4 once per week in 28-day cycle, for up to 6 cycles.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Dose escalation, Cohort 5</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Drug: SON-DP 3 participants with solid tumor will be treated with SON-DP by 90-minute IV infusion in the cohort 5 at dose level 3 twice per week in 28-day cycle, for up to 6 cycles.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Dose escalation, Cohort 6</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Drug: SON-DP 3 participants with solid tumor will be treated with SON-DP by 90-minute IV infusion in the cohort 6 at dose level 4 twice per week in 28-day cycle, for up to 6 cycles.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Dose escalation, Cohort 7</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Drug: SON-DP 3 participants with solid tumor will be treated with SON-DP by 90-minute IV infusion in the cohort 7 at dose level 5 either once per week or twice per week (FINAL SCHEDULE) in 28-day cycle, for up to 6 cycles.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Dose escalation, Cohort 8</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Drug: SON-DP 3 participants with solid tumor will be treated with SON-DP by 90-minute IV infusion in the cohort 8 at dose level 6 either once per week or twice per week (FINAL SCHEDULE) in 28-day cycle, for up to 6 cycles.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Dose escalation, Cohort 9</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Drug: SON-DP 3 participants with solid tumor will be treated with SON-DP by 90-minute IV infusion in the cohort 9 at dose level 7 either once per week or twice per week (FINAL SCHEDULE) in 28-day cycle, for up to 6 cycles.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Dose escalation, Cohort 10</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Drug: SON-DP Up to 12 participants with solid tumor will be treated with SON-DP by 90-minute IV infusion at the RP2D-1 dose level using either once per week or twice per week (FINAL SCHEDULE), for up to 6 cycles.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Dose escalation, Cohort 11</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Drug: SON-DP Up to 12 participants with solid tumor will be treated with SON-DP by 90-minute IV infusion at the RP2D dose level using either once per week or twice per week (FINAL SCHEDULE), for up to 6 cycles.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Dose expansion, Arm 1</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Drug: SON-DP Up to 18 participants with breast cancer will be treated with SON-DP by 90-minute IV infusion at the RP2D dose level using the Final Schedule, for up to 6 cycles.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Dose expansion, Arm 2</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Drug: SON-DP Up to 18 participants with pancreatic cancer will be treated with SON-DP by 90-minute IV infusion at the RP2D dose level, for up to 6 cycles.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Dose expansion, Arm 3</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Drug: SON-DP Up to 18 participants with ovarian cancer will be treated with SON-DP by 90-minute IV infusion at the RP2D dose level, for up to 6 cycles.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Dose expansion, Arm 4</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Drug: SON-DP Up to 18 participants with colorectal cancer will be treated with SON-DP by 90-minute IV infusion at the RP2D dose level, for up to 6 cycles.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>SON-DP</intervention_name>
      <description>Solution for IV administration</description>
      <arm_group_label>Dose escalation, Cohort 1</arm_group_label>
      <arm_group_label>Dose escalation, Cohort 10</arm_group_label>
      <arm_group_label>Dose escalation, Cohort 11</arm_group_label>
      <arm_group_label>Dose escalation, Cohort 2</arm_group_label>
      <arm_group_label>Dose escalation, Cohort 3</arm_group_label>
      <arm_group_label>Dose escalation, Cohort 4</arm_group_label>
      <arm_group_label>Dose escalation, Cohort 5</arm_group_label>
      <arm_group_label>Dose escalation, Cohort 6</arm_group_label>
      <arm_group_label>Dose escalation, Cohort 7</arm_group_label>
      <arm_group_label>Dose escalation, Cohort 8</arm_group_label>
      <arm_group_label>Dose escalation, Cohort 9</arm_group_label>
      <arm_group_label>Dose expansion, Arm 1</arm_group_label>
      <arm_group_label>Dose expansion, Arm 2</arm_group_label>
      <arm_group_label>Dose expansion, Arm 3</arm_group_label>
      <arm_group_label>Dose expansion, Arm 4</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Signed written informed consent;&#xD;
  &#xD;
            2. Male or female participants aged ≥ 18 years;&#xD;
  &#xD;
            3. For Phase Ia: Participants with histologic diagnosis and confirmed solid tumor; For&#xD;
               Phase Ib: Participants with one of the four tumor types: breast cancer, pancreatic&#xD;
               cancer, ovarian cancer or colorectal cancer;&#xD;
  &#xD;
            4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at study entry&#xD;
               and an estimated life expectancy of at least 3 months;&#xD;
  &#xD;
            5. Agree to the placement of drug infusion venous access;&#xD;
  &#xD;
            6. For high dose group, agree for two biopsies, one at screening and one at 1st week of&#xD;
               cycle 2;&#xD;
  &#xD;
            7. Adequate hematological function;&#xD;
  &#xD;
            8. Adequate hepatic/renal function;&#xD;
  &#xD;
            9. Acceptable coagulation function;&#xD;
  &#xD;
           10. Recovered from prior treatment Adverse Effect;&#xD;
  &#xD;
           11. Effective contraception for female participant with child bearing potential&#xD;
               participants and sexually active male participants.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Participation in investigational study within 2 weeks or 5 half-lives, whichever is&#xD;
               shorter of the first dose of study treatment.&#xD;
  &#xD;
            2. Impaired cardiac function or clinically significant cardiac disease.&#xD;
  &#xD;
            3. History of stroke or clinically significant intracranial hemorrhage within 6 months&#xD;
               before first dose of study drug.&#xD;
  &#xD;
            4. Malignant disease, other than that being treated in this study.&#xD;
  &#xD;
            5. Anticancer therapy within 5 half-lives or 2 weeks (whichever is longer) prior to study&#xD;
               entry.&#xD;
  &#xD;
            6. Active infection requiring intravenous systemic antibiotic or antiviral therapy within&#xD;
               14 days prior to the first dose of study drug.&#xD;
  &#xD;
            7. Major surgery within 4 weeks of the first dose of study treatment.&#xD;
  &#xD;
            8. Any medical condition that would, in the Investigator's judgment, prevent the&#xD;
               participant's participation in the clinical study due to safety concerns, compliance&#xD;
               with clinical study procedures, or interpretation of study results.&#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>Britney Winterberger</last_name>
      <role>Study Director</role>
      <affiliation>Tigermed America LLC.</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Jianjun Wang</last_name>
      <phone>+1（248）607 8451</phone>
      <email>wangjianjun@qurgen.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Miao Xiao</last_name>
      <phone>+1 (647) 679 3483</phone>
      <email>xiaomiao@qurgen.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Banner MD Anderson Cancer Center (BMDACC)</name>
        <address>
          <city>Gilbert</city>
          <state>Arizona</state>
          <zip>85234</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Katt Mackin</last_name>
        <phone>480-256-3425</phone>
        <email>Katt.Mackin@bannerhealth.com</email>
      </contact>
      <investigator>
        <last_name>Jason Niu</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Henry Ford Health System</name>
        <address>
          <city>Detroit</city>
          <state>Michigan</state>
          <zip>48202</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Cesar Figueras</last_name>
        <phone>313-433-8915</phone>
        <email>cfiguer1@hfhs.org</email>
      </contact>
      <investigator>
        <last_name>Amy Weise</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Carolina BioOncology Institute</name>
        <address>
          <city>Huntersville</city>
          <state>North Carolina</state>
          <zip>28078</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Ashley McClain Wallace</last_name>
        <phone>980-441-1021</phone>
        <email>awallace@carolinabiooncology.org</email>
      </contact>
      <investigator>
        <last_name>John Powderly</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Stephenson Cancer Center, University of Oklahoma</name>
        <address>
          <city>Oklahoma City</city>
          <state>Oklahoma</state>
          <zip>73104</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Christina Caldwell</last_name>
        <phone>405-271-8001</phone>
        <phone_ext>48171</phone_ext>
        <email>Christina-Caldwell@ouhsc.edu</email>
      </contact>
      <investigator>
        <last_name>Susanna Ulahannan</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>MD Anderson Cancer Center</name>
        <address>
          <city>Houston</city>
          <state>Texas</state>
          <zip>77030</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Siqing Fu</last_name>
        <phone>877-632-6789</phone>
        <email>siqingfu@mdanderson.org</email>
      </contact>
      <contact_backup>
        <last_name>Jing Peng</last_name>
        <phone>713-792-2208</phone>
        <email>jingpeng@mdanderson.org</email>
      </contact_backup>
      <investigator>
        <last_name>Siqing Fu</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 19, 2023</study_first_submitted>
    <study_first_submitted_qc>August 4, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 4, 2023</last_update_submitted>
    <last_update_submitted_qc>August 4, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>SON-DP</keyword>
    <keyword>Solid Tumor</keyword>
    <keyword>Breast Cancer</keyword>
    <keyword>Pancreatic Cancer</keyword>
    <keyword>Ovarian Cancer</keyword>
    <keyword>Colorectal cancer</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Colorectal Neoplasms</mesh_term>
      <mesh_term>Pancreatic Neoplasms</mesh_term>
      <mesh_term>Ovarian Neoplasms</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
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/NCT05989724
  org study id: SON-DP-A001-ST
  nct id: NCT05989724
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  This proposed Phase I clinical trial of SON-DP is an FIH, open-label, Phase Ia/Ib dose
        escalation and expansion study to evaluate the safety, tolerability, PK, and PD of SON-DP in
        participants with relapsed/refractory/intolerant to standard of care therapies, for advanced/
        metastatic solid tumors.
  -  In an effort to overcome the major challenges of the conventional cancer cell-killing
             therapy for high side effect, drug resistance, cancer recurrence and tumor
             heterogenicity, Qurgen Inc. is developing a novel transcription factor (TF) protein
             anticancer drug, named SON-DP, to treat the Participants with relapsed and advanced
             metastatic solid tumors. Proposed as an effective therapeutic drug product for a
             cell-converting cancer therapy, SON-DP is expected to transform cancer cells in situ
             into normal tissue cells via a SON-DP induced cancer cell reprogramming and
             re-differentiation process as an innovative rationale.
  
          -  SON-DP is developed based on the rationale of cancer cell conversion into normal tissue
             cells as the primary mechanism of actions of a new cancer therapy, not by cancer
             cell-killing, the traditional goals of chemotherapy, radiation therapy, targeted therapy
             and immune therapy. Cancer cell conversion is achieved by the SON-DP induced pluripotent
             re-programming in situ inside tumor tissue into transient iPSCs (tiPSCs) that quickly
             re-differentiate into normal tissue cells induced by the differentiating resident tissue
             environment. The in situ generated tiPSCs either secrete exosomes, providing the
             embryonic stem cells (ESC)-like microenvironments to transform the surrounding cancer
             cells into normal tissue cells for an overall malignant phenotype reversion (OMPR) (an
             effect named as a bystander effect), or display a targeting effect that enables the in
             situ generated tiPSCs to track down the distant metastatic cancer cells for OMPR (an
             effect named as a tropism effect). The SON-DP-induced cell reprogramming also restored
             the mutation-caused and compromised p53 checkpoint in cancer cells to re-establish cell
             quality control system that ensures the downstream re-differentiation of the in situ
             generated tiPSCs into normal tissue cells. Overall, this SON-DP-induced re-programming
             and re-differentiation process is capable of transforming both primary and metastatic
             cancer cells into normal tissue cells.
  
          -  Preclinical studies demonstrated that treatment of tumors with SON-DP resulted in
             eradication of late-stage cancers and long term (over 3 years) survival without teratoma
             formation and cancer recurrence in multiple tumor-bearing mouse/rat (syngeneic) or human
             xenograft rodent models, providing high treatment efficacy of this cell-converting
             cancer therapy. Thus, the cell-converting cancer therapy rationale represents a new
             cancer therapeutic strategy. SON-DP was tolerated in tumor-bearing rodents, as well as
             in naïve rats, dogs, and monkeys as demonstrated by GLP-enabled (rats and dogs) and
             non-GLP (monkey) toxicity study and after repeated IV administrations at higher doses
             compared with the planned clinical dose range. Therefore, the current nonclinical
             studies, including pharmacodynamics (PD), pharmacokinetics (PK) and toxicology studies,
             support the safety and efficacy of SON-DP TF protein drug product to be used in clinical
             studies of human participants. This first-in-human (FIH) clinical study will be
             conducted in selected types of relapsed/refractory advanced/metastatic solid tumors as a
             step in demonstrating the utility of this anticancer agent.
  
          -  In this SON-DP-A001-ST clinical trial, SON-DP is given to the participants with late
             stage solid tumors through 90-minutes IV infusion either once a week or twice a week at
             first 4 dose levels during the first Phase I dose escalation stage with the purpose to
             identify the final schedule (either once a week or twice a week) for the last 3 higher
             dose levels and the recommended phase II dose (RP2D) for the second Phase Ib does
             expansion stage that will focus on 4 cancer types including breast cancer, pancreatic
             cancer, ovarian cancer and colorectal cancer.
  
          -  During Phase Ia dose escalation stage, an accelerated 3+3 design will be followed. A
             Safety Monitoring Committee (SMC) will be formed to evaluate all the safety, efficacy,
             pharmacokinetic and pharmacodynamic data of each dose level cohort to decide if the
             SON-DP dose level should be either escalated to the next dose level or de-escalated to
             one level below or determination of maximum tolerated dose (MTD) or RP2D confirmation or
             others. Phase Ia will enroll the participants with various types of solid tumors that
             metastasized and not response to standard treatment.
  
          -  During Phase Ib dose expansion stage, SON-DP will be used, at RP2D dose level, to treat
             the participants with 4 specific cancer types including breast cancer, pancreatic
             cancer, ovary cancer or colorectal cancer. Four groups of cancer cohorts will be opened
             with eligible participants who have relapsed/refractory/intolerant to standard of care
             therapies of these four advanced/metastatic solid tumors. Participants will be followed
             for safety, confirmation of the RP2D, PK, PD, and anti-tumor activity as measured by
             standard assessment tools.
  allocation: Non-Randomized
  intervention model: Sequential Assignment
  intervention model description: This is a first-in-human and first-in-class, open-label, Phase I clinical trial including a Phase Ia dose escalation stage for the participants with all solid tumor types using seven dose levels of SON-DP to determine the RP2D, MTD and DLT; and a Phase Ib dose expansion stage for the participants of four arms including breast cancer, pancreatic cancer, ovary cancer or colorectal cancer using the RP2D of SON-DP obtained from Phase Ia.
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Number of participants with AEs, with abnormal vital signs, abnormal ECG readings, abnormal clinical laboratory tests results, abnormal physical examinations and abnormal ECOG performance status.
  time frame: Up to 7 months after the first dose
  measure: MTD (Maximum tolerable dose) / RP2D (Recommended dose for phase II)
  time frame: During 28-day DLT observation period
  measure: ORR
  time frame: Up to 6 months after the first dose
  description: Objective response rate (ORR)
  measure: DCR
  time frame: Up to 6 months after the first dose
  description: Disease control rate (DCR)
  measure: DOR
  time frame: Up to 6 months after the first dose
  description: Duration of response (DoR)
  measure: TTP
  time frame: Up to 6 months after the first dose
  description: Time-to-event endpoints of time to disease progression (TTP)
  measure: PFS
  time frame: Up to 6 months after the first dose
  description: Progression-free survival (PFS)
  measure: OS
  time frame: Time Frame: Up to 12 months after the first dose
  description: Overall Survival (OS)
  measure: Cmax
  time frame: Up to 6 months after the first dose
  description: Maximum serum concentration (Cmax) of 3 proteins from SON-DP will be investigated.
  measure: Tmax
  time frame: Up to 6 months after the first dose
  description: Time to maximum serum concentration (Tmax) of 3 proteins from SON-DP will be investigated.
  measure: T1/2
  time frame: Up to 6 months after the first dose
  description: Half-life (T1/2) of 3 proteins from SON-DP will be investigated.
  measure: AUC0-t
  time frame: Up to 6 months after the first dose
  description: AUC0-t is defined as area under the serum concentration-time curve from time 0 to the time of the last measurable concentration.
  measure: CL
  time frame: Up to 6 months after the first dose
  description: Clearance (CL) in the serum of 3 proteins from SON-DP per unit of time will be investigated.
  measure: SON-DP concentration in tumor biopsy tissue
  time frame: Up to 5 weeks after the first dose
  arm group label: Dose escalation, Cohort 1
  arm group type: Experimental
  description: Drug: SON-DP
  1 participant or 3 participants with solid tumor will be treated with SON-DP by 90-minute IV infusion in the cohort 1 at dose level 1 once per week in 28-day cycle, for up to 6 cycles.
  arm group label: Dose escalation, Cohort 2
  arm group type: Experimental
  description: Drug: SON-DP
  1 participant or 3 participants with solid tumor will be treated with SON-DP by 90-minute IV infusion in the cohort 2 at dose level 2 once per week in 28-day cycle, for up to 6 cycles.
  arm group label: Dose escalation, Cohort 3
  arm group type: Experimental
  description: Drug: SON-DP 3 participants with solid tumor will be treated with SON-DP by 90-minute IV infusion in the cohort 3 at dose level 3 once per week in 28-day cycle, for up to 6 cycles.
  arm group label: Dose escalation, Cohort 4
  arm group type: Experimental
  description: Drug: SON-DP 3 participants with solid tumor will be treated with SON-DP by 90-minute IV infusion in the cohort 4 at dose level 4 once per week in 28-day cycle, for up to 6 cycles.
  arm group label: Dose escalation, Cohort 5
  arm group type: Experimental
  description: Drug: SON-DP 3 participants with solid tumor will be treated with SON-DP by 90-minute IV infusion in the cohort 5 at dose level 3 twice per week in 28-day cycle, for up to 6 cycles.
  arm group label: Dose escalation, Cohort 6
  arm group type: Experimental
  description: Drug: SON-DP 3 participants with solid tumor will be treated with SON-DP by 90-minute IV infusion in the cohort 6 at dose level 4 twice per week in 28-day cycle, for up to 6 cycles.
  arm group label: Dose escalation, Cohort 7
  arm group type: Experimental
  description: Drug: SON-DP 3 participants with solid tumor will be treated with SON-DP by 90-minute IV infusion in the cohort 7 at dose level 5 either once per week or twice per week (FINAL SCHEDULE) in 28-day cycle, for up to 6 cycles.
  arm group label: Dose escalation, Cohort 8
  arm group type: Experimental
  description: Drug: SON-DP 3 participants with solid tumor will be treated with SON-DP by 90-minute IV infusion in the cohort 8 at dose level 6 either once per week or twice per week (FINAL SCHEDULE) in 28-day cycle, for up to 6 cycles.
  arm group label: Dose escalation, Cohort 9
  arm group type: Experimental
  description: Drug: SON-DP 3 participants with solid tumor will be treated with SON-DP by 90-minute IV infusion in the cohort 9 at dose level 7 either once per week or twice per week (FINAL SCHEDULE) in 28-day cycle, for up to 6 cycles.
  arm group label: Dose escalation, Cohort 10
  arm group type: Experimental
  description: Drug: SON-DP Up to 12 participants with solid tumor will be treated with SON-DP by 90-minute IV infusion at the RP2D-1 dose level using either once per week or twice per week (FINAL SCHEDULE), for up to 6 cycles.
  arm group label: Dose escalation, Cohort 11
  arm group type: Experimental
  description: Drug: SON-DP Up to 12 participants with solid tumor will be treated with SON-DP by 90-minute IV infusion at the RP2D dose level using either once per week or twice per week (FINAL SCHEDULE), for up to 6 cycles.
  arm group label: Dose expansion, Arm 1
  arm group type: Experimental
  description: Drug: SON-DP Up to 18 participants with breast cancer will be treated with SON-DP by 90-minute IV infusion at the RP2D dose level using the Final Schedule, for up to 6 cycles.
  arm group label: Dose expansion, Arm 2
  arm group type: Experimental
  description: Drug: SON-DP Up to 18 participants with pancreatic cancer will be treated with SON-DP by 90-minute IV infusion at the RP2D dose level, for up to 6 cycles.
  arm group label: Dose expansion, Arm 3
  arm group type: Experimental
  description: Drug: SON-DP Up to 18 participants with ovarian cancer will be treated with SON-DP by 90-minute IV infusion at the RP2D dose level, for up to 6 cycles.
  arm group label: Dose expansion, Arm 4
  arm group type: Experimental
  description: Drug: SON-DP Up to 18 participants with colorectal cancer will be treated with SON-DP by 90-minute IV infusion at the RP2D dose level, for up to 6 cycles.
  intervention type: Drug
  intervention name: SON-DP
  description: Solution for IV administration
  arm group label: Dose escalation, Cohort 1
  arm group label: Dose escalation, Cohort 10
  arm group label: Dose escalation, Cohort 11
  arm group label: Dose escalation, Cohort 2
  arm group label: Dose escalation, Cohort 3
  arm group label: Dose escalation, Cohort 4
  arm group label: Dose escalation, Cohort 5
  arm group label: Dose escalation, Cohort 6
  arm group label: Dose escalation, Cohort 7
  arm group label: Dose escalation, Cohort 8
  arm group label: Dose escalation, Cohort 9
  arm group label: Dose expansion, Arm 1
  arm group label: Dose expansion, Arm 2
  arm group label: Dose expansion, Arm 3
  arm group label: Dose expansion, Arm 4
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Britney Winterberger
  role: Study Director
  affiliation: Tigermed America LLC.
  last name: Jianjun Wang
  phone: +1（248）607 8451
  email: wangjianjun@qurgen.com
  last name: Miao Xiao
  phone: +1 (647) 679 3483
  email: xiaomiao@qurgen.com
  facility: 
  status: Not yet recruiting
  contact: 
  investigator: 
  facility: 
  status: Not yet recruiting
  contact: 
  investigator: 
  facility: 
  status: Recruiting
  contact: 
  investigator: 
  facility: 
  status: Not yet recruiting
  contact: 
  investigator: 
  facility: 
  status: Not yet recruiting
  contact: 
  contact backup: 
  investigator: 
  country: United States
  responsible party type: Sponsor
  mesh term: Colorectal Neoplasms
  mesh term: Pancreatic Neoplasms
  mesh term: Ovarian Neoplasms
  sharing ipd: No