<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/NCT04471415</url>
  </required_header>
  <id_info>
    <org_study_id>DRA-104-001</org_study_id>
    <secondary_id>2020-002770-27</secondary_id>
    <nct_id>NCT04471415</nct_id>
  </id_info>
  <brief_title>Study to Investigate DRP-104 in Adults With Advanced Solid Tumors</brief_title>
  <official_title>Phase 1 and Phase 2a, First-in-human Study of DRP-104, a Glutamine Antagonist, in Adult Patients With Advanced Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dracen Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Dracen Pharmaceuticals, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to characterize the safety, tolerability, pharmacokinetics,&#xD;
      pharmaco-dynamics and preliminary anti-tumor activity of DRP-104 (sirpiglenastat)&#xD;
      administered via intravenous infusion or via subcutaneous injection as a single agent and in&#xD;
      combination with atezolizumab in patients with advanced solid tumors and to assess&#xD;
      preliminary safety and efficacy of which route of administration (intravenous or&#xD;
      subcutaneous) will be selected for further development for the one expansion of patients,&#xD;
      advanced non-small cell lung cancer (NSCLC) with defined genetic mutations.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will be conducted in 4 Parts:&#xD;
&#xD;
      Part 1: Phase 1 single-agent dose escalation of DRP-104 administered via IV infusion (Cohort&#xD;
      1a) or subQ injection (Cohort 1b and 1c) in patients with advanced solid tumors (excluding&#xD;
      primary CNS tumors and HCC):&#xD;
&#xD;
        1. Cohort 1a: IV DRP-104 dose escalation to define the IV MTD/MAD/RP2D (up to approximately&#xD;
           50 patients)&#xD;
&#xD;
        2. Cohort 1b: subQ twice weekly DRP-104 dose escalation to define the twice weekly subQ&#xD;
           MTD/MAD/RP2D (up to approximately 50 patients)&#xD;
&#xD;
        3. Cohort 1c: subQ thrice weekly DRP-104 dose escalation to define the thrice weekly subQ&#xD;
           MTD/MAD/RP2D (up to approximately 12 patients) Upon completion of Part 1, Cohort 1a, 1b,&#xD;
           and 1c, the recommended phase 2 route of administration (RP2R: IV or subQ) and schedule&#xD;
           of administration (RP2S: twice or thrice weekly) and corresponding MTD/MAD/RP2D will be&#xD;
           determined prior to starting Part 2, cohort 2. As of Version 5 of the protocol, further&#xD;
           assessment of the intravenous formulation was terminated prior to declaring MTD/MAD/RP2D&#xD;
           and the RP2R was determined to be subQ (Section 2.5.5).&#xD;
&#xD;
      Part 2, which opens to enrollment once the MTD/MAD/RP2D/RP2R of DRP-104 has been declared&#xD;
      from either Part 1-Cohort 1a, 1b, or 1c and/or the RP2R/RP2S has been determined from Part 1&#xD;
      and includes 2 specific cohorts:&#xD;
&#xD;
        1. Cohort 1: Phase 1 single-agent safety expansion of DRP-104 administered subQ (the RP2R)&#xD;
           in patients with advanced solid tumors (excluding primary CNS tumors and HCC). DRP-104&#xD;
           will be administered twice weekly subQ in this safety expansion at the twice weekly subQ&#xD;
           MTD/MAD/RP2D of DRP-104 determined in Part 1-Cohort 1b. A minimum of 14 and up to 20&#xD;
           patients will be enrolled.&#xD;
&#xD;
        2. Cohort 2: Phase 2a expansion at the MTD/MAD/RP2D/RP2R and schedule of administration&#xD;
           (subQ twice or thrice weekly) of DRP-104 in patients with locally advanced or metastatic&#xD;
           NSCLC whose tumors contain a known mutation in kelchlike ECH-associated protein 1&#xD;
           (KEAP1), nuclear factor erythroid 2-related factor 2 (NFE2L2) and/or serine/threonine&#xD;
           kinase 11 (STK11), (N=55). If the thrice weekly schedule is selected as the RP2S, a&#xD;
           safety review will be conducted after 8 patients have enrolled and are followed for at&#xD;
           least one cycle of treatment before additional patients are enrolled into Part 2-Cohort&#xD;
           2.&#xD;
&#xD;
      Part 3: Phase 1 combination dose escalation of DRP-104 and atezolizumab in patients with&#xD;
      advanced solid tumors (excluding primary CNS tumors and HCC) previously treated with an agent&#xD;
      targeting checkpoint pathway inhibition (such as anti-PD-1, anti-PD-L1, and/or anti-CTLA-4&#xD;
      antibody), starting one dose level below the MTD/MAD/RP2D (MTD-1) of the recommended phase 2&#xD;
      route and schedule of administration of singleagent DRP-104 and in combination with 1200 mg&#xD;
      atezolizumab administered via intravenous infusion on day 1 and repeated every 3 weeks (up to&#xD;
      approximately 12 patients); The dose of atezolizumab is fixed. Enrollment for Part 3 will&#xD;
      begin once at least 14 patients from either Part 1 or 2 have been treated at this dose,&#xD;
      route, and schedule for at least one cycle to ensure safety.&#xD;
&#xD;
      Part 4: Phase 1 combination safety expansion at the MTD/MAD/RP2D, route, and schedule of&#xD;
      administration of DRP-104 with atezolizumab in a similar patient population as the&#xD;
      dose-escalation (N=14 patients).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Company decision to closing study and discontinue further patient enrollment.&#xD;
  </why_stopped>
  <start_date type="Actual">August 31, 2020</start_date>
  <completion_date type="Actual">March 28, 2023</completion_date>
  <primary_completion_date type="Actual">March 28, 2023</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>Sequential Assignment</intervention_model>
    <intervention_model_description>Dose Escalation cohort, followed by Dose Expansion cohort, followed by NSCLC, and in combination with atezolizumab cohorts.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Tolerated Dose (MTD)</measure>
    <time_frame>anticipated 2 year</time_frame>
    <description>Safety</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics (PK) of DRP-104</measure>
    <time_frame>anticipated 1 year</time_frame>
    <description>To assess and compare the concentration and partitioning of DRP-104 and the metabolites M1 and DON</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax of DRP-104</measure>
    <time_frame>anticipated 1 year</time_frame>
    <description>Area under the plasma concentration versus time curve (AUC)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall Response Rate (ORR)</measure>
    <time_frame>anticipated 2 years</time_frame>
    <description>Using RECIST criteria, determine the Overall Response Rate for DRP-104 subQ in NSCLC cohort 2 (months)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR)</measure>
    <time_frame>anticipated 2 years</time_frame>
    <description>Disease Control Rate of all patient cohorts (months) for IV and SubQ administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival (PFS)</measure>
    <time_frame>anticipated 2 years</time_frame>
    <description>Using RECIST criteria to assess the time for the disease to progress during treatment with DRP-104 (months)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>anticipated 2 years</time_frame>
    <description>Defined as the time (months) from the start of treatment to death</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">61</enrollment>
  <condition>Advanced Solid Tumor</condition>
  <condition>Non Small Cell Lung Cancer Metastatic</condition>
  <arm_group>
    <arm_group_label>Part 1a &amp; Part 1b</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single-agent dose escalation of DRP-104 to define the MTD (up to approximately 50 patients) starting at Dose Level 1 of 3.3 mg/m2 via intravenous injection&#xD;
Single-agent dose escalation of DRP-104 to define the MTD (up to approximately 50 patients) starting at Dose Level 1 at 10 mg via subcutaneous injection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cohort 1: Phase 1 single-agent safety expansion of DRP-104 administered subQ (the RP2R) in patients with advanced solid tumors (excluding primary CNS tumors and HCC). DRP-104 will be administered twice weekly subQ in this safety expansion at the twice weekly subQ MTD/MAD/RP2D of DRP-104 determined in Part 1-Cohort 1b. A minimum of 14 and up to 20 patients will be enrolled.&#xD;
Cohort 2: Phase 2a expansion at the MTD/MAD/RP2D/RP2R and schedule of administration (subQ twice or thrice weekly) of DRP-104 in patients with locally advanced or metastatic NSCLC whose tumors contain a known mutation in kelchlike ECH-associated protein 1 (KEAP1), nuclear factor erythroid 2-related factor 2 (NFE2L2) and/or serine/threonine kinase 11 (STK11), (N=55). If the thrice weekly schedule is selected as the RP2S, a safety review will be conducted after 8 patients have enrolled and are followed for at least one cycle of treatment before additional patients are enrolled into Part 2-Cohort 2.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Phase 1 combination dose escalation of DRP-104 and atezolizumab in patients with advanced solid tumors (excluding primary CNS tumors and HCC) previously treated with an agent targeting checkpoint pathway inhibition (such as anti-PD-1, anti-PD-L1, and/or anti-CTLA-4 antibody), starting one dose level below the MTD/MAD/RP2D (MTD-1) of the recommended phase 2 route and schedule of administration of singleagent DRP-104 and in combination with 1200 mg atezolizumab administered via intravenous infusion on day 1 and repeated every 3 weeks (up to approximately 12 patients);</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Phase 1 combination safety expansion at the MTD/MAD/RP2D, route, and schedule of administration of DRP-104 with atezolizumab in a similar patient population as the dose-escalation (N=14 patients).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DRP-104</intervention_name>
    <description>DRP-104 administered intravenously over 1 hour, three times per week (TIW) (Monday, Wednesday, Friday) for 2 consecutive weeks, one week off&#xD;
DRP-104 administered subcutaneously twice weekly (Monday/Thursday or Tuesday/Friday) every week OR thrice weekly (Monday, Wednesday, Friday) every week</description>
    <arm_group_label>Part 1a &amp; Part 1b</arm_group_label>
    <arm_group_label>Part 2</arm_group_label>
    <arm_group_label>Part 3</arm_group_label>
    <arm_group_label>Part 4</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>atezolizumab</intervention_name>
    <description>atezolizumab administered intravenously over 1 hour at 1200 mg once every 3 weeks.</description>
    <arm_group_label>Part 3</arm_group_label>
    <arm_group_label>Part 4</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of advanced or recurrent, histologically or cytologically confirmed,&#xD;
             measurable by RECIST 1.1 metastatic or unresectable solid tumor&#xD;
&#xD;
          -  Patient must have progressed on, be intolerant of, decline, or be ineligible for, all&#xD;
             available standard of care therapies&#xD;
&#xD;
          -  Part 2: locally advanced or metastatic NSCLC with KEAP1, NFE2L2 and/or STK11 mutation&#xD;
             ; Patients must have received at least a platinum doublet chemotherapy and an&#xD;
             anti-PD-(L)1 antibody; Received up to 3 lines of systemic anticancer therapy in the&#xD;
             recurrent or metastatic setting&#xD;
&#xD;
          -  Part 3 and 4 - DRP-104 + atezolizumab Prior exposure to any checkpoint inhibitor&#xD;
             (anti-PD-1, anti-PD-L1, anti-PDL2, and/or anti-CTLA-4 antibody)&#xD;
&#xD;
          -  ECOG performance 0 or 1&#xD;
&#xD;
          -  Patient must consent to allow acquisition of existing FFPE tumor tissue; If&#xD;
             unavailable, patient must consent to new pre-treatment tumor biopsy&#xD;
&#xD;
          -  All SCCHN patient, all NSCLC patients and all patients treated with combination of&#xD;
             DRP-104 and atezolizumab will be required to undergo pre-treatment and post-treatment&#xD;
             core or excisional biopsies.&#xD;
&#xD;
          -  Pre-treatment and post-treatment core or excisional biopsies are optional for all&#xD;
             remaining patients&#xD;
&#xD;
          -  Adequate baseline organ function as defined by: Absolute neutrophil count ≥ 1.5 ×&#xD;
             109/L (1500/µL); Hemoglobin ≥ 9 g/dL (patients that require transfusion or growth&#xD;
             factors need to demonstrate stable hemoglobin of ≥ 9 g/dL over at least a 7-day period&#xD;
             after the last transfusion/growth factor injection prior to screening labs to meet&#xD;
             eligibility) ; Platelets ≥ 75 × 109/L (75,000/µL); Hepatic Total bilirubin ≤1.5 ×&#xD;
             upper limit of normal (ULN): PT/INR and PTT ≤1.5 × ULN, unless treated with warfarin;&#xD;
             AST(SGOT)/ALT(SGPT) ≤3 × ULN or ≤ 5 × ULN for patients with liver metastases;&#xD;
             Creatinine clearance ≥ 60 ml/min/1.73m2 measured or calculated&#xD;
&#xD;
          -  Cardiac QTc (Fridericia) &lt;470 ms&#xD;
&#xD;
          -  Women of child-bearing potential and men who are sexually active must agree to use one&#xD;
             highly effective method of contraception&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with primary central nervous system tumors and hepatocellular carcinoma&#xD;
&#xD;
          -  Patients with progressive or symptomatic brain metastases or leptomeningeal disease&#xD;
&#xD;
          -  Patients who have not recovered to grade 1 or baseline from adverse events (CTCAE v&#xD;
             5.0) related to prior therapy excluding alopecia, peripheral neuropathy and&#xD;
             ototoxicity, which are excluded if ≥ grade 3.&#xD;
&#xD;
          -  Lymphopenia ≤ grade 3 is allowed if not related to prior anticancer therapy. If&#xD;
             related to prior anticancer therapy, lymphopenia must resolve to ≤ grade 1 or&#xD;
             baseline.&#xD;
&#xD;
          -  Spinal cord compression not definitively treated with surgery and/or radiation&#xD;
&#xD;
          -  Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent&#xD;
             drainage&#xD;
&#xD;
          -  Prior glutaminase inhibitor use&#xD;
&#xD;
          -  Prior systemic anticancer treatment (i.e., chemotherapy, biologic therapy, monoclonal&#xD;
             antibodies, investigational agents) within 21 days or 5 half-lives, whichever is&#xD;
             shorter&#xD;
&#xD;
          -  Anti-androgen therapies for prostate cancer, such as bicalutamide, within 4 weeks&#xD;
             prior to enrollment&#xD;
&#xD;
          -  Patients must have recovered from all AEs due to previous therapies to CTCAE v 5.0&#xD;
             grade 1 or baseline, excluding, alopecia, peripheral neuropathy and ototoxicity, which&#xD;
             must be at least grade 2 or baseline&#xD;
&#xD;
          -  Prior small port palliative radiotherapy within 14 days of start of Cycle 1&#xD;
&#xD;
          -  Any major surgery within 21 days from start of Cycle 1&#xD;
&#xD;
          -  Secondary malignancy that is progressing or has required active treatment within the&#xD;
             past 3 years, except basal cell carcinoma of the skin, squamous cell carcinoma of the&#xD;
             skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have&#xD;
             undergone potentially curative therapy&#xD;
&#xD;
          -  Has a known history of HIV or HBV&#xD;
&#xD;
          -  Gastrointestinal (GI) function impairment or GI disease&#xD;
&#xD;
          -  Significant, uncontrolled heart disease and/or cardiac repolarization abnormality&#xD;
&#xD;
          -  Exclusion specific to only Part 3 and 4 (DRP-104 combined with atezolizumab):&#xD;
&#xD;
          -  History of severe allergic, anaphylactic to chimeric or humanized antibodies or fusion&#xD;
             proteins&#xD;
&#xD;
          -  Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster&#xD;
             ovary cells&#xD;
&#xD;
          -  Prior anti-PD-1, anti-PD-L1 and/or anti CTLA4- agent, patient must not have had a&#xD;
             serious (&gt; Grade 3) immune-related AE requiring treatment&#xD;
&#xD;
          -  History of autoimmune disease except hypothyroidism on thyroid replacement hormone&#xD;
             therapy, idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis&#xD;
             obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active&#xD;
             pneumonitis&#xD;
&#xD;
          -  Patients with underlying condition requiring systemic corticosteroids (&gt;10 mg daily&#xD;
             prednisone equivalents) or other immunosuppressive medications or other systemic&#xD;
             immunosuppressant medications may be enrolled in the study after approval by the&#xD;
             Medical Monitor&#xD;
&#xD;
          -  History of organ transplantation and/or hematopoietic stem cell transplantation&#xD;
&#xD;
          -  Evidence or history of active or latent tuberculosis infection&#xD;
&#xD;
          -  Administration of a live, attenuated vaccine within 4 weeks before Cycle 1 Day 1&#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>Sunil Sharma, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>HonorHealth Director</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>HonorHealth</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85258</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCLA</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AdventHealth Medical Group</name>
      <address>
        <city>Kissimmee</city>
        <state>Florida</state>
        <zip>34747</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialist</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32827</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins Kimmel Institute</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NYU Langone</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Icahn School of Medicine at Mount Sinai</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029-6574</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of North Carolina</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27514</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ohio State University Comprehensive Cancer Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NEXT Oncology</name>
      <address>
        <city>Fairfax</city>
        <state>Virginia</state>
        <zip>22031</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrum fur Integrieerte Onkologie</name>
      <address>
        <city>Cologne</city>
        <zip>50924</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Cancer Center NCT</name>
      <address>
        <city>Dresden</city>
        <zip>01307</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Frankfurt</name>
      <address>
        <city>Frankfurt</city>
        <zip>60590</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Klinikum Wuerzburg</name>
      <address>
        <city>Würzburg</city>
        <zip>97070</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Center Singapore</name>
      <address>
        <city>Singapore</city>
        <zip>169610</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital University Vall d'Hebron</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital 12 de Octubre</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>100</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taipei Veterans General Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>112</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>Singapore</country>
    <country>Spain</country>
    <country>Taiwan</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.dracenpharma.com/</url>
    <description>Company website with scientific background on DRP-104</description>
  </link>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>June 25, 2020</study_first_submitted>
  <study_first_submitted_qc>July 14, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 15, 2020</study_first_posted>
  <last_update_submitted>June 9, 2023</last_update_submitted>
  <last_update_submitted_qc>June 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 12, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atezolizumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04471415
org study id: DRA-104-001
secondary id: 2020-002770-27
nct id: NCT04471415
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to characterize the safety, tolerability, pharmacokinetics,
      pharmaco-dynamics and preliminary anti-tumor activity of DRP-104 (sirpiglenastat)
      administered via intravenous infusion or via subcutaneous injection as a single agent and in
      combination with atezolizumab in patients with advanced solid tumors and to assess
      preliminary safety and efficacy of which route of administration (intravenous or
      subcutaneous) will be selected for further development for the one expansion of patients,
      advanced non-small cell lung cancer (NSCLC) with defined genetic mutations.
This study will be conducted in 4 Parts:

      Part 1: Phase 1 single-agent dose escalation of DRP-104 administered via IV infusion (Cohort
      1a) or subQ injection (Cohort 1b and 1c) in patients with advanced solid tumors (excluding
      primary CNS tumors and HCC):

        1. Cohort 1a: IV DRP-104 dose escalation to define the IV MTD/MAD/RP2D (up to approximately
           50 patients)

        2. Cohort 1b: subQ twice weekly DRP-104 dose escalation to define the twice weekly subQ
           MTD/MAD/RP2D (up to approximately 50 patients)

        3. Cohort 1c: subQ thrice weekly DRP-104 dose escalation to define the thrice weekly subQ
           MTD/MAD/RP2D (up to approximately 12 patients) Upon completion of Part 1, Cohort 1a, 1b,
           and 1c, the recommended phase 2 route of administration (RP2R: IV or subQ) and schedule
           of administration (RP2S: twice or thrice weekly) and corresponding MTD/MAD/RP2D will be
           determined prior to starting Part 2, cohort 2. As of Version 5 of the protocol, further
           assessment of the intravenous formulation was terminated prior to declaring MTD/MAD/RP2D
           and the RP2R was determined to be subQ (Section 2.5.5).

      Part 2, which opens to enrollment once the MTD/MAD/RP2D/RP2R of DRP-104 has been declared
      from either Part 1-Cohort 1a, 1b, or 1c and/or the RP2R/RP2S has been determined from Part 1
      and includes 2 specific cohorts:

        1. Cohort 1: Phase 1 single-agent safety expansion of DRP-104 administered subQ (the RP2R)
           in patients with advanced solid tumors (excluding primary CNS tumors and HCC). DRP-104
           will be administered twice weekly subQ in this safety expansion at the twice weekly subQ
           MTD/MAD/RP2D of DRP-104 determined in Part 1-Cohort 1b. A minimum of 14 and up to 20
           patients will be enrolled.

        2. Cohort 2: Phase 2a expansion at the MTD/MAD/RP2D/RP2R and schedule of administration
           (subQ twice or thrice weekly) of DRP-104 in patients with locally advanced or metastatic
           NSCLC whose tumors contain a known mutation in kelchlike ECH-associated protein 1
           (KEAP1), nuclear factor erythroid 2-related factor 2 (NFE2L2) and/or serine/threonine
           kinase 11 (STK11), (N=55). If the thrice weekly schedule is selected as the RP2S, a
           safety review will be conducted after 8 patients have enrolled and are followed for at
           least one cycle of treatment before additional patients are enrolled into Part 2-Cohort
           2.

      Part 3: Phase 1 combination dose escalation of DRP-104 and atezolizumab in patients with
      advanced solid tumors (excluding primary CNS tumors and HCC) previously treated with an agent
      targeting checkpoint pathway inhibition (such as anti-PD-1, anti-PD-L1, and/or anti-CTLA-4
      antibody), starting one dose level below the MTD/MAD/RP2D (MTD-1) of the recommended phase 2
      route and schedule of administration of singleagent DRP-104 and in combination with 1200 mg
      atezolizumab administered via intravenous infusion on day 1 and repeated every 3 weeks (up to
      approximately 12 patients); The dose of atezolizumab is fixed. Enrollment for Part 3 will
      begin once at least 14 patients from either Part 1 or 2 have been treated at this dose,
      route, and schedule for at least one cycle to ensure safety.

      Part 4: Phase 1 combination safety expansion at the MTD/MAD/RP2D, route, and schedule of
      administration of DRP-104 with atezolizumab in a similar patient population as the
      dose-escalation (N=14 patients).
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: Dose Escalation cohort, followed by Dose Expansion cohort, followed by NSCLC, and in combination with atezolizumab cohorts.
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerated Dose (MTD)
time frame: anticipated 2 year
description: Safety
measure: Pharmacokinetics (PK) of DRP-104
time frame: anticipated 1 year
description: To assess and compare the concentration and partitioning of DRP-104 and the metabolites M1 and DON
measure: Cmax of DRP-104
time frame: anticipated 1 year
description: Area under the plasma concentration versus time curve (AUC)
measure: Overall Response Rate (ORR)
time frame: anticipated 2 years
description: Using RECIST criteria, determine the Overall Response Rate for DRP-104 subQ in NSCLC cohort 2 (months)
measure: Disease Control Rate (DCR)
time frame: anticipated 2 years
description: Disease Control Rate of all patient cohorts (months) for IV and SubQ administration
measure: Progression-Free Survival (PFS)
time frame: anticipated 2 years
description: Using RECIST criteria to assess the time for the disease to progress during treatment with DRP-104 (months)
measure: Overall Survival (OS)
time frame: anticipated 2 years
description: Defined as the time (months) from the start of treatment to death
arm group label: Part 1a & Part 1b
arm group type: Experimental
description: Single-agent dose escalation of DRP-104 to define the MTD (up to approximately 50 patients) starting at Dose Level 1 of 3.3 mg/m2 via intravenous injection
Single-agent dose escalation of DRP-104 to define the MTD (up to approximately 50 patients) starting at Dose Level 1 at 10 mg via subcutaneous injection
arm group label: Part 2
arm group type: Experimental
description: Cohort 1: Phase 1 single-agent safety expansion of DRP-104 administered subQ (the RP2R) in patients with advanced solid tumors (excluding primary CNS tumors and HCC). DRP-104 will be administered twice weekly subQ in this safety expansion at the twice weekly subQ MTD/MAD/RP2D of DRP-104 determined in Part 1-Cohort 1b. A minimum of 14 and up to 20 patients will be enrolled.
Cohort 2: Phase 2a expansion at the MTD/MAD/RP2D/RP2R and schedule of administration (subQ twice or thrice weekly) of DRP-104 in patients with locally advanced or metastatic NSCLC whose tumors contain a known mutation in kelchlike ECH-associated protein 1 (KEAP1), nuclear factor erythroid 2-related factor 2 (NFE2L2) and/or serine/threonine kinase 11 (STK11), (N=55). If the thrice weekly schedule is selected as the RP2S, a safety review will be conducted after 8 patients have enrolled and are followed for at least one cycle of treatment before additional patients are enrolled into Part 2-Cohort 2.
arm group label: Part 3
arm group type: Experimental
description: Phase 1 combination dose escalation of DRP-104 and atezolizumab in patients with advanced solid tumors (excluding primary CNS tumors and HCC) previously treated with an agent targeting checkpoint pathway inhibition (such as anti-PD-1, anti-PD-L1, and/or anti-CTLA-4 antibody), starting one dose level below the MTD/MAD/RP2D (MTD-1) of the recommended phase 2 route and schedule of administration of singleagent DRP-104 and in combination with 1200 mg atezolizumab administered via intravenous infusion on day 1 and repeated every 3 weeks (up to approximately 12 patients);
arm group label: Part 4
arm group type: Experimental
description: Phase 1 combination safety expansion at the MTD/MAD/RP2D, route, and schedule of administration of DRP-104 with atezolizumab in a similar patient population as the dose-escalation (N=14 patients).
intervention type: Drug
intervention name: DRP-104
description: DRP-104 administered intravenously over 1 hour, three times per week (TIW) (Monday, Wednesday, Friday) for 2 consecutive weeks, one week off
DRP-104 administered subcutaneously twice weekly (Monday/Thursday or Tuesday/Friday) every week OR thrice weekly (Monday, Wednesday, Friday) every week
arm group label: Part 1a & Part 1b
arm group label: Part 2
arm group label: Part 3
arm group label: Part 4
intervention type: Biological
intervention name: atezolizumab
description: atezolizumab administered intravenously over 1 hour at 1200 mg once every 3 weeks.
arm group label: Part 3
arm group label: Part 4
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sunil Sharma, MD
role: Principal Investigator
affiliation: HonorHealth Director
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country: Germany
country: Singapore
country: Spain
country: Taiwan
country: United States
url: http://www.dracenpharma.com/
description: Company website with scientific background on DRP-104
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Atezolizumab
sharing ipd: No