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/NCT05961839</url>
    </required_header>
    <id_info>
      <org_study_id>SGR-2921-101</org_study_id>
      <nct_id>NCT05961839</nct_id>
    </id_info>
    <brief_title>Study of SGR-2921 in Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome</brief_title>
    <official_title>A First-In-Human, Phase 1, Dose Escalation Study of SGR-2921 as Monotherapy In Subjects With Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Schrödinger, Inc.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Schrödinger, 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 evaluate safety and tolerability and to determine the maximum&#xD;
        tolerated dose (MTD) and/or recommended dose (RD) of SGR-2921.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a study of SGR-2921, an oral, small molecule inhibitor of cell division cycle&#xD;
        7-related protein kinase (CDC7), in subjects with Relapsed/Refractory (R/R) Acute Myeloid&#xD;
        Leukemia (AML) or Myelodysplastic Syndrome (MDS) to evaluate the safety, pharmacokinetics&#xD;
        (PK), pharmacodynamics (PD), maximum tolerated dose (MTD) and/or recommended dose (RD) of&#xD;
        SGR-2921.&#xD;
  &#xD;
        Exploratory cohorts may evaluate additional PK, PD, preliminary anti-tumor activity, and&#xD;
        safety to establish the SGR-2921 RD. A planned amendment will evaluate SGR-2921 in&#xD;
        combination with other approved AML/MDS treatments such as hypomethylating agents (HMA), BCL2&#xD;
        inhibitors, IDH inhibitors or FLT3 inhibitors, in patients with AML and/or MDS.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 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>
    <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>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Dose Limiting Toxicities</measure>
      <time_frame>From first dose until the end of Cycle 1 (approximately 28 days, up to 42 days).</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Adverse Events</measure>
      <time_frame>Throughout the study, up to 26 months.</time_frame>
      <description>Incidence, nature, and severity of adverse events (AEs) as assessed by the NCI CTCAE v5.0.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Electrocardiograms in Singlicate and Triplicate</measure>
      <time_frame>Throughout the study, up to 26 months.</time_frame>
      <description>Uncorrected QT interval, QTcF, PR duration, QRS interval, and RR interval.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>SGR-2921 Maximal Plasma Concentration (Cmax)</measure>
      <time_frame>Throughout the study, up to 26 months.</time_frame>
      <description>Concentrations of SGR-2921 in plasma are measured at various timepoints following its administration to calculate typical exposure/PK parameters, including, but not limited to, the maximal plasma concentration (Cmax).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>SGR-2921 Minimum Plasma Concentration (Cmin)</measure>
      <time_frame>Throughout the study, up to 26 months.</time_frame>
      <description>Concentrations of SGR-2921 in plasma are measured at various timepoints following its administration to calculate typical exposure/PK parameters, including, but not limited to, the minimum plasma concentration (Cmin).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>SGR-2921 Time to Maximal Plasma Concentration (tmax)</measure>
      <time_frame>Throughout the study, up to 26 months.</time_frame>
      <description>Concentrations of SGR-2921 in plasma are measured at various timepoints following its administration to calculate typical exposure/PK parameters, including, but not limited to, the time to maximal plasma concentration (tmax).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>SGR-2921 Area Under the Concentration Versus Time Curve (AUC)</measure>
      <time_frame>Throughout the study, up to 26 months.</time_frame>
      <description>Concentrations of SGR-2921 in plasma are measured at various timepoints following its administration to calculate typical exposure/PK parameters, including, but not limited to, the area under the concentration versus time curve (AUC).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Composite Complete Remission (CR) Rate for Subjects with AML</measure>
      <time_frame>Throughout the study, up to 26 months.</time_frame>
      <description>The percentage of subjects with CR, CR with Partial Hematologic Recovery (CRh), and CR with Incomplete Blood Count Recovery (CRi).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Objective Response Rate (ORR) for Subjects with AML</measure>
      <time_frame>Throughout the study, up to 26 months.</time_frame>
      <description>The percentage of subjects achieving CR, CRh, CRi, morphologic leukemia-free state (MLFS) and Partial Response (PR).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Objective Response Rate (ORR) for Subjects with MDS</measure>
      <time_frame>Throughout the study, up to 26 months.</time_frame>
      <description>The percentage of subjects achieving CR and PR.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of Response (DOR) for Subjects with AML</measure>
      <time_frame>Throughout the study, up to 26 months.</time_frame>
      <description>The time from first response (CR, CRh, CRi, MLFS, or PR) to the date of initial objectively documented progression or death due to any cause, whichever occurs first.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of Response (DOR) for subjects with MDS</measure>
      <time_frame>Throughout the study, up to 26 months.</time_frame>
      <description>The time from first response (CR or PR) to the date of initial objectively documented progression or death due to any cause, whichever occurs first.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">50</enrollment>
    <condition>Acute Myeloid Leukemia</condition>
    <condition>High-Risk and Very High-Risk Myelodysplastic Syndromes</condition>
    <arm_group>
      <arm_group_label>Dose Escalation in the Absence of Specific Azole Antifungal Treatments</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Up to 9 dose levels will be evaluated in subjects not receiving specific azole antifungal treatment.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Dose Escalation in the Presence of Specific Azole Antifungal Treatments</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Up to 9 dose levels will be evaluated in subjects receiving specific azole antifungal treatment.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>SGR-2921</intervention_name>
      <description>SGR-2921 will be administered orally.</description>
      <arm_group_label>Dose Escalation in the Absence of Specific Azole Antifungal Treatments</arm_group_label>
      <arm_group_label>Dose Escalation in the Presence of Specific Azole Antifungal Treatments</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  ≥ 18 years of age.&#xD;
  &#xD;
            -  Life expectancy ≥ 8 weeks.&#xD;
  &#xD;
            -  Confirmed diagnosis of R/R AML or High Risk (HR) and Very High Risk (VHR) MDS.&#xD;
  &#xD;
            -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Active malignancies within two years prior to the first dose, or requiring ongoing&#xD;
               treatment, not related to AML or MDS.&#xD;
  &#xD;
            -  Clinical evidence of central nervous system (CNS) or pulmonary leukostasis, ≥ Grade 3&#xD;
               disseminated intravascular coagulation, or active CNS leukemia.&#xD;
  &#xD;
            -  Use of experimental drug, or therapy, or anti-cancer therapy within 14 days or 5&#xD;
               half-lives of the first dose of study drug.&#xD;
  &#xD;
            -  QT interval corrected for heart rate per Fridericia's formula ≥470 msec during&#xD;
               screening ECG.&#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>Daniel Weiss, M.D.</last_name>
      <role>Study Director</role>
      <affiliation>Schrödinger, Inc.</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Study Physician</last_name>
      <phone>+15032991150</phone>
      <email>sdgr-trials-group@schrodinger.com</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 17, 2023</study_first_submitted>
    <study_first_submitted_qc>July 17, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">July 27, 2023</study_first_posted>
    <last_update_submitted>August 1, 2023</last_update_submitted>
    <last_update_submitted_qc>August 1, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 3, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>MDS</keyword>
    <keyword>Relapsed or Refractory AML</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Leukemia</mesh_term>
      <mesh_term>Leukemia, Myeloid</mesh_term>
      <mesh_term>Leukemia, Myeloid, Acute</mesh_term>
      <mesh_term>Preleukemia</mesh_term>
      <mesh_term>Myelodysplastic Syndromes</mesh_term>
      <mesh_term>Syndrome</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/NCT05961839
  org study id: SGR-2921-101
  nct id: NCT05961839
  lead sponsor: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: No
  The purpose of this study is to evaluate safety and tolerability and to determine the maximum
        tolerated dose (MTD) and/or recommended dose (RD) of SGR-2921.
  This is a study of SGR-2921, an oral, small molecule inhibitor of cell division cycle
        7-related protein kinase (CDC7), in subjects with Relapsed/Refractory (R/R) Acute Myeloid
        Leukemia (AML) or Myelodysplastic Syndrome (MDS) to evaluate the safety, pharmacokinetics
        (PK), pharmacodynamics (PD), maximum tolerated dose (MTD) and/or recommended dose (RD) of
        SGR-2921.
  
        Exploratory cohorts may evaluate additional PK, PD, preliminary anti-tumor activity, and
        safety to establish the SGR-2921 RD. A planned amendment will evaluate SGR-2921 in
        combination with other approved AML/MDS treatments such as hypomethylating agents (HMA), BCL2
        inhibitors, IDH inhibitors or FLT3 inhibitors, in patients with AML and/or MDS.
  allocation: Non-Randomized
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Dose Limiting Toxicities
  time frame: From first dose until the end of Cycle 1 (approximately 28 days, up to 42 days).
  measure: Adverse Events
  time frame: Throughout the study, up to 26 months.
  description: Incidence, nature, and severity of adverse events (AEs) as assessed by the NCI CTCAE v5.0.
  measure: Electrocardiograms in Singlicate and Triplicate
  time frame: Throughout the study, up to 26 months.
  description: Uncorrected QT interval, QTcF, PR duration, QRS interval, and RR interval.
  measure: SGR-2921 Maximal Plasma Concentration (Cmax)
  time frame: Throughout the study, up to 26 months.
  description: Concentrations of SGR-2921 in plasma are measured at various timepoints following its administration to calculate typical exposure/PK parameters, including, but not limited to, the maximal plasma concentration (Cmax).
  measure: SGR-2921 Minimum Plasma Concentration (Cmin)
  time frame: Throughout the study, up to 26 months.
  description: Concentrations of SGR-2921 in plasma are measured at various timepoints following its administration to calculate typical exposure/PK parameters, including, but not limited to, the minimum plasma concentration (Cmin).
  measure: SGR-2921 Time to Maximal Plasma Concentration (tmax)
  time frame: Throughout the study, up to 26 months.
  description: Concentrations of SGR-2921 in plasma are measured at various timepoints following its administration to calculate typical exposure/PK parameters, including, but not limited to, the time to maximal plasma concentration (tmax).
  measure: SGR-2921 Area Under the Concentration Versus Time Curve (AUC)
  time frame: Throughout the study, up to 26 months.
  description: Concentrations of SGR-2921 in plasma are measured at various timepoints following its administration to calculate typical exposure/PK parameters, including, but not limited to, the area under the concentration versus time curve (AUC).
  measure: Composite Complete Remission (CR) Rate for Subjects with AML
  time frame: Throughout the study, up to 26 months.
  description: The percentage of subjects with CR, CR with Partial Hematologic Recovery (CRh), and CR with Incomplete Blood Count Recovery (CRi).
  measure: Objective Response Rate (ORR) for Subjects with AML
  time frame: Throughout the study, up to 26 months.
  description: The percentage of subjects achieving CR, CRh, CRi, morphologic leukemia-free state (MLFS) and Partial Response (PR).
  measure: Objective Response Rate (ORR) for Subjects with MDS
  time frame: Throughout the study, up to 26 months.
  description: The percentage of subjects achieving CR and PR.
  measure: Duration of Response (DOR) for Subjects with AML
  time frame: Throughout the study, up to 26 months.
  description: The time from first response (CR, CRh, CRi, MLFS, or PR) to the date of initial objectively documented progression or death due to any cause, whichever occurs first.
  measure: Duration of Response (DOR) for subjects with MDS
  time frame: Throughout the study, up to 26 months.
  description: The time from first response (CR or PR) to the date of initial objectively documented progression or death due to any cause, whichever occurs first.
  arm group label: Dose Escalation in the Absence of Specific Azole Antifungal Treatments
  arm group type: Experimental
  description: Up to 9 dose levels will be evaluated in subjects not receiving specific azole antifungal treatment.
  arm group label: Dose Escalation in the Presence of Specific Azole Antifungal Treatments
  arm group type: Experimental
  description: Up to 9 dose levels will be evaluated in subjects receiving specific azole antifungal treatment.
  intervention type: Drug
  intervention name: SGR-2921
  description: SGR-2921 will be administered orally.
  arm group label: Dose Escalation in the Absence of Specific Azole Antifungal Treatments
  arm group label: Dose Escalation in the Presence of Specific Azole Antifungal Treatments
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Daniel Weiss, M.D.
  role: Study Director
  affiliation: Schrödinger, Inc.
  last name: Study Physician
  phone: +15032991150
  email: sdgr-trials-group@schrodinger.com
  responsible party type: Sponsor
  mesh term: Leukemia
  mesh term: Leukemia, Myeloid
  mesh term: Leukemia, Myeloid, Acute
  mesh term: Preleukemia
  mesh term: Myelodysplastic Syndromes
  mesh term: Syndrome
  sharing ipd: No