<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/NCT04504942</url>
  </required_header>
  <id_info>
    <org_study_id>CD09_Basket</org_study_id>
    <nct_id>NCT04504942</nct_id>
  </id_info>
  <brief_title>Basket Study of Leronlimab (PRO 140) in Patients With CCR5+ Locally Advanced or Metastatic Solid Tumors</brief_title>
  <official_title>Basket Study of Leronlimab (PRO 140) in Patients With CCR5+ Locally Advanced or Metastatic Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>CytoDyn, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Amarex Clinical Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>CytoDyn, Inc.</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a single arm phase II study with 30 patients of leronlimab (PRO 140) in patients with&#xD;
      CCR5+ locally advanced or metastatic solid tumors.&#xD;
&#xD;
      Leronlimab (PRO 140) will be administered subcutaneously as weekly dose of 525 mg until&#xD;
      disease progression or intolerable toxicity. Subjects participating in this study will be&#xD;
      allowed to receive/continue standard-of-care chemotherapy or radotherapy as per the dosing&#xD;
      schedule included on the package insert.&#xD;
&#xD;
      In this study, patients will be evaluated for tumor response approximately every 3 months or&#xD;
      according to institution's standard practice by CT, PET/CT or MRI with contrast (per treating&#xD;
      investigator's discretion) using the same method as at baseline.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">May 1, 2020</start_date>
  <completion_date type="Anticipated">July 15, 2022</completion_date>
  <primary_completion_date type="Actual">November 7, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number, frequency, and severity of adverse events (AEs)</measure>
    <time_frame>From the time of first treatment until 12 weeks after study treatment completion</time_frame>
    <description>Note: Adverse events will follow National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal laboratory tests results</measure>
    <time_frame>Up to 12 weeks after study treatment completion</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in Eastern Cooperative Oncology Group (ECOG) performance status from baseline to subsequent scheduled visits</measure>
    <time_frame>Up to 12 weeks after study treatment completion</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS) defined as time in months from the date of first study treatment to the date of disease progression or death from any cause, whichever comes first.</measure>
    <time_frame>The time in months from start of treatment to progression or death will be measured for all patients who receive at least one dose of study drug. Patients will be followed up to 2 years after completion of treatment.</time_frame>
    <description>Note: All patients who receive at least one dose of leronlimab will be included in the primary analyses of PFS. The Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria will be used for objective tumor response assessment (when disease is measurable and non- measurable);</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall response rate (ORR, defined as CR + PR) in subjects with CCR5+ locally advanced or metastatic solid tumors treated with leronlimab</measure>
    <time_frame>The time in months from start of treatment to progression or death will be measured for all patients who receive at least one dose of study drug. Patients will be followed up to 2 years after completion of treatment.</time_frame>
    <description>Note: Overall response rate is defined as the proportion of patients who achieve an overall response of complete response or partial response in the total number of evaluable patients, assessed by RECIST v1.1. Clinical benefit rate is defined as the proportion of patients who achieve an overall response of complete response or partial response or stable disease in the total number of evaluable patients, assessed by RECIST v1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Benefit Rate (CBR, defined as CR + PR + SD) in subjects with CCR5+ locally advanced or metastatic solid tumors treated with leronlimab</measure>
    <time_frame>The time in months from start of treatment to progression or death will be measured for all patients who receive at least one dose of study drug. Patients will be followed up to 2 years after completion of treatment.</time_frame>
    <description>Note: Overall response rate is defined as the proportion of patients who achieve an overall response of complete response or partial response in the total number of evaluable patients, assessed by RECIST v1.1. Clinical benefit rate is defined as the proportion of patients who achieve an overall response of complete response or partial response or stable disease in the total number of evaluable patients, assessed by RECIST v1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to new metastases (TTNM)</measure>
    <time_frame>The time in months from start of treatment to progression or death will be measured for all patients who receive at least one dose of study drug.</time_frame>
    <description>Note: Recorded time from baseline metastatic disease (at time of enrollment) to the time of development of new metastasis in different site, assessed up to 6 months. New metastases in same site will be also recorded.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The change from baseline in circulating tumor cells (CTC) level in the peripheral blood.</measure>
    <time_frame>From date of first treatment until the date of first documented progression or date of death from any cause, whichever came first.</time_frame>
    <description>Note: Reported unit of measure will be the number of CTCs/milliliter. CTCs enumeration will be performed at baseline and at the time of response assessment, assessed up to 6 months. Fraction of baseline positive and change from ≥5 CTCs will be recorded and reported</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival defined as time in months from the date of first study treatment to the date of death</measure>
    <time_frame>The time in months from start of treatment to progression or death will be measured for all patients who receive at least one dose of study drug. Patients will be followed up to 2 years after completion of treatment.</time_frame>
    <description>Note: Patients will be followed from the start of treatment until 2 years post-treatment or death, whichever occurs first, and average survival time will be measured.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Solid Tumor, Adult</condition>
  <arm_group>
    <arm_group_label>Leronlimab 525mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Leronlimab (PRO) 140 is a humanized IgG4, monoclonal antibody (mAb) to the C-C chemokine receptor type 5 (CCR5)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Leronlimab</intervention_name>
    <description>Drug: Leronlimab 525mg</description>
    <arm_group_label>Leronlimab 525mg</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Must have a histologically or cytologically confirmed diagnosis of locally advanced or&#xD;
             metastatic solid tumors:&#xD;
&#xD;
               1. who have disease progression on standard therapy,&#xD;
&#xD;
               2. who are receiving a standard anticancer treatment but no subsequent approved&#xD;
                  treatment would be available upon progression,&#xD;
&#xD;
               3. who are unable to receive standard therapy, or&#xD;
&#xD;
               4. for whom standard therapy does not exist.&#xD;
&#xD;
          2. Demonstrate CCR5 + by IHC (&gt;10% of primary or metastatic tumor cells shows membranous&#xD;
             staining and/or high predominance of CCR5+ tumor-infiltrating leukocytes completed at&#xD;
             the reference laboratory of Dr. Hallgeir Rui at Medical College of Wisconsin).&#xD;
&#xD;
             Note: This test will be done as part of the pre-screening period. It will be performed&#xD;
             in archival metastatic tissue. If archival tissue is not available then, fresh biopsy&#xD;
             will be done;&#xD;
&#xD;
          3. Be willing to provide tissue from a newly obtained core or excisional biopsy of a&#xD;
             tumor lesion (in case archival tissue is not available);&#xD;
&#xD;
          4. Patients must have measurable disease based on RECIST v1.1;&#xD;
&#xD;
          5. ≥ 18 years of age;&#xD;
&#xD;
          6. Patients must exhibit a/an ECOG performance status of 0-1;&#xD;
&#xD;
          7. Life expectancy of at least 6 months;&#xD;
&#xD;
          8. Patients must have adequate organ and bone marrow function within 28 days prior to&#xD;
             registration, as defined below:&#xD;
&#xD;
               -  leukocytes ≥ 3,000/mcL;&#xD;
&#xD;
               -  absolute neutrophil count ≥ 1,500/mcL;&#xD;
&#xD;
               -  platelets ≥ 100,000/mcL;&#xD;
&#xD;
               -  total bilirubin: within normal institutional limits;&#xD;
&#xD;
               -  AST(SGOT) and ALT(SPGT) ≤ 2.5 X institutional upper limit of normal (ULN)&#xD;
                  (applicable to all patients, irrespective of liver disease or metastasis); and&#xD;
&#xD;
               -  creatinine: within normal institutional limits.&#xD;
&#xD;
          9. Clinically normal resting 12-lead ECG at Screening Visit or, if abnormal, considered&#xD;
             not clinically significant by the Principal Investigator.&#xD;
&#xD;
         10. Females of child-bearing potential (FOCBP) and males must agree to use two medically&#xD;
             accepted methods of contraception with hormonal or barrier method of birth control, or&#xD;
             abstinence, prior to study entry, for the duration of study participation and for 60&#xD;
             days after the last dose of study drug (Refer to Appendix 1). Should a female patient&#xD;
             become pregnant or suspect she is pregnant while participating in this study, she&#xD;
             should inform her treating physician immediately. NOTE: A FOCBP is any woman&#xD;
             (regardless of sexual orientation, having undergone a tubal ligation, or remaining&#xD;
             celibate by choice) who meets the following criteria:&#xD;
&#xD;
               -  Has not undergone a hysterectomy or bilateral oophorectomy; and&#xD;
&#xD;
               -  Has had menses at any time in the preceding 12 consecutive months (and therefore&#xD;
                  has not been naturally postmenopausal for &gt; 12 months).&#xD;
&#xD;
         11. FOCBP must have a negative serum pregnancy test at Screening Visit and negative urine&#xD;
             pregnancy test prior to receiving the first dose of study drug; and&#xD;
&#xD;
         12. Patients must have the ability to understand and the willingness to sign a written&#xD;
             informed consent prior to registration on study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Is currently participating and receiving study therapy or has participated in a study&#xD;
             of an investigational agent and received study therapy or used an investigational&#xD;
             device within 28 days prior to enrollment;&#xD;
&#xD;
          2. Patients who have a history of allergic reactions attributed to compounds of similar&#xD;
             chemical or biologic composition to leronlimab (PRO 140) are not eligible;&#xD;
&#xD;
          3. Patients who have had prior exposure to CCR5 antagonists are not eligible;&#xD;
&#xD;
          4. Has known active central nervous system (CNS) metastases and/or carcinomatous&#xD;
             meningitis. Note: Subjects with previously treated brain metastases may participate&#xD;
             provided they are stable (without evidence of progression by imaging for at least four&#xD;
             weeks prior to the first dose of trial treatment and any neurologic symptoms have&#xD;
             returned to baseline), have no evidence of new or enlarging brain metastases, and are&#xD;
             not using steroids for at least 7 days prior to trial treatment. This exception does&#xD;
             not include carcinomatous meningitis which is excluded regardless of clinical&#xD;
             stability;&#xD;
&#xD;
          5. Has a history or current evidence of any condition, therapy, or laboratory abnormality&#xD;
             that might confound the results of the trial, interfere with the subject's&#xD;
             participation for the full duration of the trial, or is not in the best interest of&#xD;
             the subject to participate, in the opinion of the treating investigator;&#xD;
&#xD;
          6. Has known psychiatric or substance abuse disorders that would interfere with&#xD;
             cooperation with the requirements of the trial; and&#xD;
&#xD;
          7. Is pregnant or breastfeeding, or expecting to conceive or have children within the&#xD;
             projected duration of the trial, starting with the pre-screening or screening visit&#xD;
             through the duration of study participation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Quest Clinical Research</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94122</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>June 10, 2020</study_first_submitted>
  <study_first_submitted_qc>August 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2020</study_first_posted>
  <last_update_submitted>June 30, 2022</last_update_submitted>
  <last_update_submitted_qc>June 30, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 1, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leronlimab</mesh_term>
  </intervention_browse>
  <!-- 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/NCT04504942
org study id: CD09_Basket
nct id: NCT04504942
lead sponsor: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This is a single arm phase II study with 30 patients of leronlimab (PRO 140) in patients with
      CCR5+ locally advanced or metastatic solid tumors.

      Leronlimab (PRO 140) will be administered subcutaneously as weekly dose of 525 mg until
      disease progression or intolerable toxicity. Subjects participating in this study will be
      allowed to receive/continue standard-of-care chemotherapy or radotherapy as per the dosing
      schedule included on the package insert.

      In this study, patients will be evaluated for tumor response approximately every 3 months or
      according to institution's standard practice by CT, PET/CT or MRI with contrast (per treating
      investigator's discretion) using the same method as at baseline.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number, frequency, and severity of adverse events (AEs)
time frame: From the time of first treatment until 12 weeks after study treatment completion
description: Note: Adverse events will follow National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
measure: Incidence of abnormal laboratory tests results
time frame: Up to 12 weeks after study treatment completion
measure: Changes in Eastern Cooperative Oncology Group (ECOG) performance status from baseline to subsequent scheduled visits
time frame: Up to 12 weeks after study treatment completion
measure: Progression free survival (PFS) defined as time in months from the date of first study treatment to the date of disease progression or death from any cause, whichever comes first.
time frame: The time in months from start of treatment to progression or death will be measured for all patients who receive at least one dose of study drug. Patients will be followed up to 2 years after completion of treatment.
description: Note: All patients who receive at least one dose of leronlimab will be included in the primary analyses of PFS. The Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria will be used for objective tumor response assessment (when disease is measurable and non- measurable);
measure: Overall response rate (ORR, defined as CR + PR) in subjects with CCR5+ locally advanced or metastatic solid tumors treated with leronlimab
time frame: The time in months from start of treatment to progression or death will be measured for all patients who receive at least one dose of study drug. Patients will be followed up to 2 years after completion of treatment.
description: Note: Overall response rate is defined as the proportion of patients who achieve an overall response of complete response or partial response in the total number of evaluable patients, assessed by RECIST v1.1. Clinical benefit rate is defined as the proportion of patients who achieve an overall response of complete response or partial response or stable disease in the total number of evaluable patients, assessed by RECIST v1.1.
measure: Clinical Benefit Rate (CBR, defined as CR + PR + SD) in subjects with CCR5+ locally advanced or metastatic solid tumors treated with leronlimab
time frame: The time in months from start of treatment to progression or death will be measured for all patients who receive at least one dose of study drug. Patients will be followed up to 2 years after completion of treatment.
description: Note: Overall response rate is defined as the proportion of patients who achieve an overall response of complete response or partial response in the total number of evaluable patients, assessed by RECIST v1.1. Clinical benefit rate is defined as the proportion of patients who achieve an overall response of complete response or partial response or stable disease in the total number of evaluable patients, assessed by RECIST v1.1.
measure: Time to new metastases (TTNM)
time frame: The time in months from start of treatment to progression or death will be measured for all patients who receive at least one dose of study drug.
description: Note: Recorded time from baseline metastatic disease (at time of enrollment) to the time of development of new metastasis in different site, assessed up to 6 months. New metastases in same site will be also recorded.
measure: The change from baseline in circulating tumor cells (CTC) level in the peripheral blood.
time frame: From date of first treatment until the date of first documented progression or date of death from any cause, whichever came first.
description: Note: Reported unit of measure will be the number of CTCs/milliliter. CTCs enumeration will be performed at baseline and at the time of response assessment, assessed up to 6 months. Fraction of baseline positive and change from ≥5 CTCs will be recorded and reported
measure: Overall survival defined as time in months from the date of first study treatment to the date of death
time frame: The time in months from start of treatment to progression or death will be measured for all patients who receive at least one dose of study drug. Patients will be followed up to 2 years after completion of treatment.
description: Note: Patients will be followed from the start of treatment until 2 years post-treatment or death, whichever occurs first, and average survival time will be measured.
arm group label: Leronlimab 525mg
arm group type: Experimental
description: Leronlimab (PRO) 140 is a humanized IgG4, monoclonal antibody (mAb) to the C-C chemokine receptor type 5 (CCR5)
intervention type: Drug
intervention name: Leronlimab
description: Drug: Leronlimab 525mg
arm group label: Leronlimab 525mg
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Leronlimab