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/NCT06014658</url>
    </required_header>
    <id_info>
      <org_study_id>MBRC-101-001</org_study_id>
      <nct_id>NCT06014658</nct_id>
    </id_info>
    <brief_title>Safety &amp; PK of MBRC-101 in Advanced Refractory Solid Tumors</brief_title>
    <official_title>A Multicenter, Open-label, Phase 1/1b Dose Finding, Safety, and Pharmacokinetic Study of MBRC-101, an Anti-EphA5 Monomethyl Auristatin E (MMAE) Antibody Drug Conjugate, in Advanced Refractory Solid Tumors</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>MBrace Therapeutics</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>MBrace Therapeutics</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>
        This is a first-in-human (FIH), open label Phase 1/1b study in patients with advanced&#xD;
        metastatic solid tumors refractory to standard treatment. Phase 1 will identify potential&#xD;
        optimal biologically relevant doses (OBRD) and the maximum tolerated dose (MTD) of MBRC-101&#xD;
        at one 1 or more dosing regimens. Phase 1b will evaluate the safety and preliminary clinical&#xD;
        activity of MBRC-101 at potential OBRDs. Phase 1 and Phase 1b will both characterize single&#xD;
        and multiple-dose PK profiles and evaluate incidence and persistence of anti-MBRC-101 Ab.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Phase 1, dose escalation, will enroll approximately 30 patients with advanced or metastatic&#xD;
        solid tumors refractory to standard therapy. EphA5 expression will not be required for&#xD;
        enrollment into Phase 1 but will be assessed retrospectively.&#xD;
  &#xD;
        Phase1b, the dose expansion phase will evaluate the safety and preliminary clinical activity&#xD;
        of MBRC-101 at potential OBRDs and dosing regimens in patients with advanced or metastatic&#xD;
        solid tumors refractory to standard therapy. Phase 1b will enroll 3 expansion cohorts of ≈ 20&#xD;
        patients per cohort (n ≈ 60 total).&#xD;
  &#xD;
        Safety will be monitored by the Safety Review Committee (SRC) at each dose escalation in&#xD;
        Phase 1 and at regular intervals throughout Phase 1b.&#xD;
  &#xD;
        Overall Response Rate (ORR), Progression Free Survival (PFS), Response Rate (RR), Overall&#xD;
        Survival (OS), and Complete and Partial response (CR and PR) will be used to evaluate&#xD;
        efficacy per RECIST v1.1 criteria based on the results of positron emission tomography and&#xD;
        computed tomography (PET-CT), computerized tomography (CT), and magnetic resonance imaging&#xD;
        (MRI) scans.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">October 2025</completion_date>
    <primary_completion_date type="Anticipated">July 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>Occurrence of treatment-emergent adverse events (TEAEs)</measure>
      <time_frame>Up to 24 Months</time_frame>
      <description>TEAEs will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.5.0.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Occurrence of dose limiting toxicities (DLTs) during the DLT evaluation period</measure>
      <time_frame>21 Days</time_frame>
      <description>The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Objective Response Rate (ORR)</measure>
      <time_frame>Up to 24 Months</time_frame>
      <description>ORR is defined as the percentage of participants who have a partial response (PR) or better according to the response evaluation criteria in solid tumors (RECIST) version 1.1.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of Response (DOR)</measure>
      <time_frame>Up to 24 Months</time_frame>
      <description>DOR will be calculated among responders (PR or better) from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease per RECIST version 1.1 response criteria, or death due to any cause, whichever occurs first.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression-Free Survival (PFS)</measure>
      <time_frame>Up to 24 Months</time_frame>
      <description>PFS will be calculated from the date of first dose of MBRC-101 to the date of first documented evidence of progressive disease as defined by RECIST version 1.1 response criteria or death due to any cause, whichever occurs first.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">90</enrollment>
    <condition>Cancer</condition>
    <arm_group>
      <arm_group_label>Phase 1 Dose Escalation</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Phase 1b Expansion</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Antibody-Drug Conjugate</intervention_name>
      <description>MBRC-101: AN ANTI-EPHA5 MONOMETHYL AURISTATIN E (MMAE) ANTIBODY DRUG CONJUGATE</description>
      <arm_group_label>Phase 1 Dose Escalation</arm_group_label>
      <arm_group_label>Phase 1b Expansion</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Provide written consent on an Informed Consent Form (ICF), approved by an&#xD;
               Institutional Review Board (IRB)/Independent Ethics Committee (IEC), prior to any&#xD;
               study-specific evaluation. Patients should have the ability to read and understand the&#xD;
               ICF, ask for any clarifications from the study staff, and be able to comply with all&#xD;
               planned study procedures.&#xD;
  &#xD;
            2. 18 years of age or older at the time of informed consent.&#xD;
  &#xD;
            3. Female patients must be at least 2 years postmenopausal (defined as 2 years without&#xD;
               menses), surgically sterile (at least 6 months prior to dosing; must be documented) or&#xD;
               practicing effective contraception (must agree to use 2 forms of contraception, 1 of&#xD;
               which must be a barrier method) and willing to continue to use effective contraception&#xD;
               for the duration of study participation and for 6 months after the final dose of study&#xD;
               drug.&#xD;
  &#xD;
               Female patients must be nonlactating and have a negative serum pregnancy test result&#xD;
               at screening and baseline.&#xD;
  &#xD;
            4. Male patients must agree to use effective contraception (must agree to use 2 forms of&#xD;
               contraception, 1 of which must be a barrier method) for the duration of study&#xD;
               participation and for 6 months after the final dose of study drug.&#xD;
  &#xD;
            5. Have a histologic or cytologic diagnosis of malignant solid tumor for which there are&#xD;
               no standard of care treatment options known to confer a clinical benefit or for which&#xD;
               the patient is ineligible or declines.&#xD;
  &#xD;
                 1. For Phase 1 dose escalation: histologic or cytologic diagnosis of malignant solid&#xD;
                    tumor of any type. The Sponsor may remove specific tumor indications based on&#xD;
                    emerging, real-time study data.&#xD;
  &#xD;
                 2. For Phase 1b dose expansion:&#xD;
  &#xD;
               i. Cohort A: Histologic or cytologic diagnosis of NSLC (adenocarcinoma and SCC).&#xD;
  &#xD;
               ii. Cohort B: Histologic or cytologic diagnosis of TNBC or HR positive, HER2 negative&#xD;
               breast cancer.&#xD;
  &#xD;
               iii. Cohort C: Histologic or cytologic diagnosis of solid tumors irrespective of&#xD;
               histologic tissue type (i.e., tumor agnostic), excluding NSCLC and breast cancer. The&#xD;
               Sponsor may add or remove specific tumor indications based on emerging, real-time&#xD;
               study data.&#xD;
  &#xD;
            6. For Phase 1 and Phase 1b, patients must submit a tumor tissue sample (formalin-fixed&#xD;
               paraffin-embedded [FFPE] or fresh biopsy tissue) for analysis of EphA5 expression&#xD;
               based on IHC.&#xD;
  &#xD;
                 1. For Dose Escalation (Phase 1), tumor EphA5 expression will not be required for&#xD;
                    enrollment.&#xD;
  &#xD;
                 2. For Cohorts A and B of Dose Expansion (Phase 1b), tumor EphA5 expression will not&#xD;
                    be required for enrollment.&#xD;
  &#xD;
                 3. For Cohort C (basket cohort) of Dose Expansion (Phase 1b), patients must have&#xD;
                    tumor tissue positive (IHC H-score ≥ 1) for EphA5 expression (as measured by a&#xD;
                    Sponsor-designated central laboratory using archival or fresh primary or&#xD;
                    metastatic invasive tumor tissue submitted for analysis). Tumor biopsies&#xD;
                    involving significant risk procedure should not be performed to assess&#xD;
                    eligibility. Confirmation of EphA5 expression in tumor tissue is required prior&#xD;
                    to patient enrollment in Cohort C (basket cohort) only.&#xD;
  &#xD;
            7. For Dose Escalation (Phase 1), patients may have evaluable disease or measurable&#xD;
               disease according to Response Evaluation Criteria In Solid Tumors [RECIST] v1.1). For&#xD;
               Dose Expansion (Phase 1b), patients must have measurable disease according to RECIST&#xD;
               v1.1.&#xD;
  &#xD;
            8. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.&#xD;
  &#xD;
            9. Life expectancy ≥ 3 months as assessed by the investigator.&#xD;
  &#xD;
           10. Hematologic function, as follows (no red blood cell (RBC) or platelet transfusions are&#xD;
               allowed within 14 days of the first dose of MBRC-101):&#xD;
  &#xD;
                 1. Absolute neutrophil count (ANC) ≥ 1.0 × 109/L&#xD;
  &#xD;
                 2. Platelet count ≥ 75 × 109/L&#xD;
  &#xD;
                 3. Hemoglobin ≥ 9 g/dL&#xD;
  &#xD;
           11. Creatinine clearance of ≥ 30 mL/min by the Cockcroft-Gault equation or as measured by&#xD;
               24-hour urine collection.&#xD;
  &#xD;
           12. Total bilirubin ≤ 1.5 × upper limit normal (ULN).&#xD;
  &#xD;
           13. AST ≤ 3.0 × ULN.&#xD;
  &#xD;
           14. ALT ≤ 3.0 × ULN.&#xD;
  &#xD;
           15. International normalised ratio (INR) &lt; 1.5 (or ≤ 3.0 if on therapeutic&#xD;
               anticoagulation).&#xD;
  &#xD;
           16. Treatment with other agents for cancer, if received, must have been discontinued ≥ 2&#xD;
               weeks prior to first dose of study drug. Prior ADC therapy is allowed. Prior agents&#xD;
               conjugated to MMAE are allowed for Phase 1 but not Phase 1b.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Preexisting sensory neuropathy Grade ≥ 2.&#xD;
  &#xD;
            2. Preexisting motor neuropathy Grade ≥ 2.&#xD;
  &#xD;
            3. Uncontrolled central nervous system metastases.&#xD;
  &#xD;
            4. Use of any investigational drug within 14 days prior to the first dose of study drug.&#xD;
  &#xD;
            5. Any anticancer therapy within 14 days prior to the first dose of study drug,&#xD;
               including:&#xD;
  &#xD;
               small molecules, immunotherapy, chemotherapy, monoclonal antibody therapy,&#xD;
               radiotherapy or any other agents to treat cancer (anti-hormonal therapy given for&#xD;
               advanced prostate cancer or as adjuvant therapy for early stage, hormone receptor (HR)&#xD;
               positive breast cancer is not considered cancer therapy for the purpose of this&#xD;
               protocol).&#xD;
  &#xD;
            6. Patients with immunotherapy related AEs requiring high doses of steroids (≥ 40 mg/day&#xD;
               of prednisone) are not eligible.&#xD;
  &#xD;
            7. Strong CYP3A or P-gp inhibitors inhibitors within 14 days prior to the first dose of&#xD;
               study drug.&#xD;
  &#xD;
            8. Thromboembolic events and/or bleeding disorders ≤ 14 days (e.g., venous&#xD;
               thromboembolism [VTE] or pulmonary embolism [or PE]) prior to the first dose of study&#xD;
               drug.&#xD;
  &#xD;
            9. Documented history of a cerebral vascular event (stroke or transient ischemic attack),&#xD;
               unstable angina, myocardial infarction, or cardiac symptoms (including congestive&#xD;
               heart failure) consistent with New York Heart Association Class 3-4 within 6 months&#xD;
               prior to the first dose of MBRC-101.&#xD;
  &#xD;
           10. A baseline QT interval as corrected by Fridericia's formula (QTcF) &gt; 450 msec.&#xD;
  &#xD;
           11. Human immunodeficiency virus (HIV) infection with 1 or more of the following:&#xD;
  &#xD;
                 1. Acquired immunodeficiency syndrome (AIDs)-defining opportunistic infection within&#xD;
                    6 months of the start of screening;&#xD;
  &#xD;
                 2. A change in antiretroviral therapy within 3 months of the start of screening;&#xD;
  &#xD;
                 3. Receiving antiretroviral therapy that may interfere with study drug;&#xD;
  &#xD;
                 4. CD4 count &lt; 350 at screening.&#xD;
  &#xD;
           12. Active or symptomatic viral hepatitis. Patients who have been properly treated for&#xD;
               hepatitis C infection can be included if they do not have active hepatitis C.&#xD;
  &#xD;
           13. Known sensitivity to any of the ingredients of the investigational product MBRC-101.&#xD;
  &#xD;
           14. Major surgery within 28 days prior to first dose of study drug.&#xD;
  &#xD;
           15. History of another malignancy within 3 years before the first dose of study drug, or&#xD;
               any evidence of residual disease from a previously diagnosed malignancy. Allowed&#xD;
               exceptions are patients with:&#xD;
  &#xD;
                 1. Non-melanoma skin cancer considered completely cured;&#xD;
  &#xD;
                 2. Localized prostate cancer treated with curative intent with no evidence of&#xD;
                    progression;&#xD;
  &#xD;
                 3. Low-risk or very low-risk (per standard clinical guidelines) localized prostate&#xD;
                    cancer under active surveillance without immediate intent to treat;&#xD;
  &#xD;
                 4. Malignancy that is otherwise considered cured with minimal risk of recurrence.&#xD;
  &#xD;
           16. Currently receiving systemic antimicrobial treatment for active infection (bacterial,&#xD;
               viral, or fungal) at the time of first dose of MBRC-101. Routine antimicrobial&#xD;
               prophylaxis is permitted.&#xD;
  &#xD;
           17. For Phase 1b dose expansion, prior ADC therapy is not allowed if the agent is&#xD;
               conjugated to MMAE. Prior agents conjugated to MMAE are allowed for Phase 1.&#xD;
  &#xD;
           18. Condition or situation which, in the investigator's opinion, may put the patient at&#xD;
               significant risk, may confound the study results, or may interfere significantly with&#xD;
               patient's participation in the study.&#xD;
  &#xD;
           19. Any medical, psychiatric, addictive or other kind of disorder which compromises the&#xD;
               ability of the patient to give written informed consent and/or to comply with&#xD;
               procedures.&#xD;
  &#xD;
           20. Active ocular surface disease at baseline or any components of the ophthalmologic&#xD;
               history which, in the investigator's opinion, may place the patient at significant&#xD;
               risk.&#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_contact>
      <last_name>Kellogg Parsons, MD, M.H.S.</last_name>
      <phone>8585688531</phone>
      <email>kparsons@mbracetrx.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Carolina BioOncology Institute</name>
        <address>
          <city>Huntersville</city>
          <state>North Carolina</state>
          <zip>28078</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>John D Powderly</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>NEXT Oncology</name>
        <address>
          <city>Austin</city>
          <state>Texas</state>
          <zip>78758</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Andrae Vandross</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>NEXT Oncology</name>
        <address>
          <city>Irving</city>
          <state>Texas</state>
          <zip>75039</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Shiraj Sen</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>NEXT Oncology</name>
        <address>
          <city>Fairfax</city>
          <state>Virginia</state>
          <zip>22031</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Adham Salkeni</last_name>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 1, 2023</study_first_submitted>
    <study_first_submitted_qc>August 23, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 28, 2023</study_first_posted>
    <last_update_submitted>September 6, 2023</last_update_submitted>
    <last_update_submitted_qc>September 6, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 8, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Antibodies</mesh_term>
      <mesh_term>Immunoconjugates</mesh_term>
    </intervention_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/NCT06014658
  org study id: MBRC-101-001
  nct id: NCT06014658
  lead sponsor: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: No
  This is a first-in-human (FIH), open label Phase 1/1b study in patients with advanced
        metastatic solid tumors refractory to standard treatment. Phase 1 will identify potential
        optimal biologically relevant doses (OBRD) and the maximum tolerated dose (MTD) of MBRC-101
        at one 1 or more dosing regimens. Phase 1b will evaluate the safety and preliminary clinical
        activity of MBRC-101 at potential OBRDs. Phase 1 and Phase 1b will both characterize single
        and multiple-dose PK profiles and evaluate incidence and persistence of anti-MBRC-101 Ab.
  Phase 1, dose escalation, will enroll approximately 30 patients with advanced or metastatic
        solid tumors refractory to standard therapy. EphA5 expression will not be required for
        enrollment into Phase 1 but will be assessed retrospectively.
  
        Phase1b, the dose expansion phase will evaluate the safety and preliminary clinical activity
        of MBRC-101 at potential OBRDs and dosing regimens in patients with advanced or metastatic
        solid tumors refractory to standard therapy. Phase 1b will enroll 3 expansion cohorts of ≈ 20
        patients per cohort (n ≈ 60 total).
  
        Safety will be monitored by the Safety Review Committee (SRC) at each dose escalation in
        Phase 1 and at regular intervals throughout Phase 1b.
  
        Overall Response Rate (ORR), Progression Free Survival (PFS), Response Rate (RR), Overall
        Survival (OS), and Complete and Partial response (CR and PR) will be used to evaluate
        efficacy per RECIST v1.1 criteria based on the results of positron emission tomography and
        computed tomography (PET-CT), computerized tomography (CT), and magnetic resonance imaging
        (MRI) scans.
  allocation: Non-Randomized
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Occurrence of treatment-emergent adverse events (TEAEs)
  time frame: Up to 24 Months
  description: TEAEs will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.5.0.
  measure: Occurrence of dose limiting toxicities (DLTs) during the DLT evaluation period
  time frame: 21 Days
  description: The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.
  measure: Objective Response Rate (ORR)
  time frame: Up to 24 Months
  description: ORR is defined as the percentage of participants who have a partial response (PR) or better according to the response evaluation criteria in solid tumors (RECIST) version 1.1.
  measure: Duration of Response (DOR)
  time frame: Up to 24 Months
  description: DOR will be calculated among responders (PR or better) from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease per RECIST version 1.1 response criteria, or death due to any cause, whichever occurs first.
  measure: Progression-Free Survival (PFS)
  time frame: Up to 24 Months
  description: PFS will be calculated from the date of first dose of MBRC-101 to the date of first documented evidence of progressive disease as defined by RECIST version 1.1 response criteria or death due to any cause, whichever occurs first.
  arm group label: Phase 1 Dose Escalation
  arm group type: Experimental
  arm group label: Phase 1b Expansion
  arm group type: Experimental
  intervention type: Drug
  intervention name: Antibody-Drug Conjugate
  description: MBRC-101: AN ANTI-EPHA5 MONOMETHYL AURISTATIN E (MMAE) ANTIBODY DRUG CONJUGATE
  arm group label: Phase 1 Dose Escalation
  arm group label: Phase 1b Expansion
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Kellogg Parsons, MD, M.H.S.
  phone: 8585688531
  email: kparsons@mbracetrx.com
  facility: 
  contact: 
  facility: 
  contact: 
  facility: 
  contact: 
  facility: 
  contact: 
  country: United States
  responsible party type: Sponsor
  mesh term: Antibodies
  mesh term: Immunoconjugates
  sharing ipd: No