<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/NCT03297424</url>
  </required_header>
  <id_info>
    <org_study_id>PLX124-01</org_study_id>
    <nct_id>NCT03297424</nct_id>
  </id_info>
  <brief_title>A Study of PLX2853 in Advanced Malignancies.</brief_title>
  <official_title>A Phase 1b Dose-escalation Study to Assess Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of PLX2853 in Subjects With Advanced Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Opna-IO LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Opna-IO LLC</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 research study is to evaluate safety, pharmacokinetics, pharmacodynamics&#xD;
      and preliminary efficacy of the investigational drug PLX2853 in subjects with advanced&#xD;
      malignancies.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 12, 2017</start_date>
  <completion_date type="Actual">June 7, 2021</completion_date>
  <primary_completion_date type="Actual">June 7, 2021</primary_completion_date>
  <phase>Phase 1</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 of participants with treatment-related adverse events as assessed by CTCAE v5.0.</measure>
    <time_frame>First dose of study drug through at least 30 days after end of treatment.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the concentration-time curve (AUC) of PLX2853.</measure>
    <time_frame>From first dose of PLX2853 up to 30 days after end of treatment.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum observed concentration (Cmax) of PLX2853.</measure>
    <time_frame>From first dose of PLX2853 up to 30 days after end of treatment.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to peak concentration (Tmax) of PLX2853.</measure>
    <time_frame>From first dose of PLX2853 up to 30 days after end of treatment.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Half life (t1/2) of PLX2853.</measure>
    <time_frame>From first dose of PLX2853 up to 30 days after end of treatment.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants who experience dose limiting toxicity as defined in the protocol.</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>The highest dose level at which less than 2 of 6 participants or less than 33% of participants (if cohort is expanded beyond 6) experience a dose limiting toxicity will be considered the maximum tolerated dose / recommended phase 2 dose.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in disease burden using RECIST 1.1 (solid tumors) or Lugano criteria (NHL).</measure>
    <time_frame>Up to 2 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall response rate (ORR) defined according to standard criteria for the relevant malignancy [Phase1b]</measure>
    <time_frame>From the first dose of study drug until the date of documented response to treatment, assessed up to 2 years.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR)</measure>
    <time_frame>DOR defined as the time from the initial objective response to disease progression or death, whichever occurs first, assessed up to 2 years.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival (PFS)</measure>
    <time_frame>PFS time is defined as the time from the first dose of PLX2853 to disease progression or death, whichever occurs first, assessed up to 2 years.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>From the first dose of study drug until the date of death from any cause, assessed up to 2 years.</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">49</enrollment>
  <condition>Small Cell Lung Cancer</condition>
  <condition>Uveal Melanoma</condition>
  <condition>Ovarian Clear Cell Carcinoma</condition>
  <condition>Non-Hodgkin Lymphoma</condition>
  <condition>Advanced Malignancies</condition>
  <condition>Solid Tumor</condition>
  <condition>Diffuse Large B Cell Lymphoma</condition>
  <condition>Follicular Lymphoma</condition>
  <arm_group>
    <arm_group_label>PLX2853</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Phase 1b (Dose Escalation): Approximately 45 subjects with advanced malignancies to establish the MTD/RP2D. Up to 6 additional subjects may be enrolled at the MTD/RP2D as a dose confirmation.&#xD;
Phase 2a (Dose Expansion): There will be 5 total expansion cohorts. Either 10 or 29 subjects per cohort in each of 4 expansion cohorts: advanced SCLC, uveal melanoma, OCCC, and any other advanced malignancy with a known ARID1A mutation (between 40 to 116 subjects total for the solid tumor expansion phase). For the 5th expansion cohort, up to 20 subjects may be enrolled for NHL.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PLX2853</intervention_name>
    <description>tablets</description>
    <arm_group_label>PLX2853</arm_group_label>
    <other_name>PLX2853 tablets</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Confirmed diagnosis of one of the following:&#xD;
&#xD;
          -  Phase 1b:&#xD;
&#xD;
               -  Histologically confirmed advanced refractory solid tumor that is measurable or&#xD;
                  evaluable per RECIST 1.1 criteria.&#xD;
&#xD;
               -  Histologically confirmed NHL: diffuse large B-cell lymphoma and follicular&#xD;
                  lymphoma (Grade 1-3A) which is measurable or evaluable per Lugano criteria, has&#xD;
                  progressed following at least 1 line of prior anticancer therapy.&#xD;
&#xD;
          -  Phase 2a: Patients with various solid tumors or NHL who have received prior therapy.&#xD;
&#xD;
          -  Age ≥18 years&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1&#xD;
&#xD;
          -  Adequate organ function as appropriate for the disease under study. All screening&#xD;
             laboratory tests should be performed within 10 days of treatment initiation.&#xD;
&#xD;
          -  Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test at&#xD;
             Screening (≤7 days prior to 1st study drug dose) and must agree to use an effective&#xD;
             form of contraception from the time of the negative pregnancy test up to 90 days after&#xD;
             the last dose of study drug. Effective forms of contraception include abstinence,&#xD;
             hormonal contraceptive in conjunction with a barrier method, or a double barrier&#xD;
             method. Women of non-child-bearing potential may be included if they are either&#xD;
             surgically sterile or have been postmenopausal for ≥1 year.&#xD;
&#xD;
          -  Fertile men must agree to use an effective method of birth control during the study&#xD;
             and for up to 90 days after the last dose of study drug.&#xD;
&#xD;
          -  All associated clinically significant drug-related toxicity from previous cancer&#xD;
             therapy must be resolved prior to study treatment administration (alopecia, erectile&#xD;
             impotence, hot flashes, decreased libido, and neuropathy is allowed).&#xD;
&#xD;
          -  Willingness and ability to provide written informed consent prior to any study-related&#xD;
             procedures and to comply with all study requirements&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior exposure to a bromodomain inhibitor, such as OTX-015 or CPI-0610&#xD;
&#xD;
          -  Known uncontrolled fungal, bacterial, and/or viral infection ≥Grade 2&#xD;
&#xD;
          -  Autoimmune hemolytic anemia or autoimmune thrombocytopenia&#xD;
&#xD;
          -  Presence of symptomatic or uncontrolled central nervous system or leptomeningeal&#xD;
             metastases&#xD;
&#xD;
          -  Known or suspected allergy to the investigational agent or any agent given in&#xD;
             association with this trial&#xD;
&#xD;
          -  Clinically significant cardiac disease such as cardiac arrhythmias including&#xD;
             bradyarrhythmias and/or subjects who require anti-arrhythmic therapy (excluding beta&#xD;
             blockers or digoxin), including uncontrolled hypertension or arterial or venous&#xD;
             thrombotic events. Subjects with controlled atrial fibrillation are not excluded.&#xD;
&#xD;
          -  Inability to take oral medication or significant nausea and vomiting, malabsorption,&#xD;
             or significant small bowel resection that, in the opinion of the Investigator, would&#xD;
             preclude adequate absorption&#xD;
&#xD;
          -  Non-healing wound, ulcer, or bone fracture&#xD;
&#xD;
          -  Subject has known human immunodeficiency virus (HIV), hepatitis B or hepatitis C&#xD;
             infection or is known to be a carrier of hepatitis B or C. Subjects who are positive&#xD;
             for hepatitis C virus (HCV) antibody must be negative for HCV by polymerase chain&#xD;
             reaction (PCR) to be eligible. Subjects with occult or prior hepatitis B virus (HBV)&#xD;
             infection (defined as positive total hepatitis B core antibody (HBcAb) and negative&#xD;
             hepatitis B surface antigen (HBsAg) may be included if HBV DNA is undetectable. These&#xD;
             subjects must be willing to undergo additional testing per local standard of care.&#xD;
&#xD;
          -  Active second malignancy with the exception of any of the following:&#xD;
&#xD;
               -  Adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or&#xD;
                  in situ cervical cancer;&#xD;
&#xD;
               -  Adequately treated Stage I cancer from which the subject is currently in&#xD;
                  remission and has been in remission for ≥2 years;&#xD;
&#xD;
               -  Low-risk prostate cancer with Gleason score &lt;7 and prostate-specific antigen &lt;10&#xD;
                  ng/mL; or&#xD;
&#xD;
               -  Any other cancer from which the patient has been disease-free for ≥3 years.&#xD;
&#xD;
          -  Subjects with documented hepatic metastases involving &gt;50% of the hepatic parenchyma,&#xD;
             or any individual liver metastasis &gt;5 cm, as assessed by the investigator.&#xD;
&#xD;
          -  Major surgery or significant traumatic injury within 14 days prior to Cycle 1 Day 1&#xD;
&#xD;
          -  Receipt of anti-cancer therapy with insufficient washout prior to Cycle 1 Day 1: No&#xD;
             chemotherapy, radiation therapy, or small molecule tyrosine kinase inhibitors (TKI)&#xD;
             for the treatment of cancer within 14 days or 5 half-lives (whichever is shorter) of&#xD;
             Cycle 1 Day 1. Certain standard of care hormonal anticancer therapies, such as agents&#xD;
             targeted to GnRH for the treatment of prostate cancer or aromatase inhibitors for the&#xD;
             treatment of breast cancer, may be permitted after consultation with the medical&#xD;
             monitor. No immune therapy or other biologic therapy (other monoclonal antibodies or&#xD;
             antibody-drug conjugates [ADCs]) for the treatment of cancer within 28 days of Cycle 1&#xD;
             Day 1.&#xD;
&#xD;
          -  Subject is receiving systemic steroids at doses greater than the equivalent of&#xD;
             prednisone 10 mg daily, with the exception of intermittent use for the treatment of&#xD;
             emesis&#xD;
&#xD;
          -  Subject is participating in any other therapeutic clinical study (observational or&#xD;
             registry trials are allowed)&#xD;
&#xD;
          -  Female subjects who are pregnant or breast-feeding&#xD;
&#xD;
          -  Presence of any other medical, psychological, familial, sociological, or geographic&#xD;
             condition potentially hampering compliance with the study protocol or would interfere&#xD;
             with the study endpoints or the subject's ability to participate in the study in the&#xD;
             judgement of the investigator&#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>Honor Health</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85258</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sylvester Comprehensive Cancer Center / University of Miami Miller School of Medicine</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>South Texas Accelerated Research Therapeutics (START)</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Cancer Specialists</name>
      <address>
        <city>Fairfax</city>
        <state>Virginia</state>
        <zip>22031</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>September 8, 2017</study_first_submitted>
  <study_first_submitted_qc>September 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 29, 2017</study_first_posted>
  <last_update_submitted>July 20, 2022</last_update_submitted>
  <last_update_submitted_qc>July 20, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 25, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>PLX2853</keyword>
  <keyword>Small cell lung cancer (SCLC)</keyword>
  <keyword>Uveal Melanoma</keyword>
  <keyword>Ovarian Clear Cell Carcinoma</keyword>
  <keyword>Non-Hodgkin Lymphoma</keyword>
  <keyword>Advanced Malignancies</keyword>
  <keyword>Solid Tumor</keyword>
  <keyword>Diffuse Large B Cell Lymphoma (DLBCL)</keyword>
  <keyword>Follicular Lymphoma (FL)</keyword>
  <keyword>ARID1A</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Melanoma</mesh_term>
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Lymphoma, Follicular</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
    <mesh_term>Lymphoma, B-Cell</mesh_term>
    <mesh_term>Small Cell Lung Carcinoma</mesh_term>
    <mesh_term>Lymphoma, Large B-Cell, Diffuse</mesh_term>
    <mesh_term>Adenomyoepithelioma</mesh_term>
    <mesh_term>Adenocarcinoma, Clear Cell</mesh_term>
  </condition_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/NCT03297424
org study id: PLX124-01
nct id: NCT03297424
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this research study is to evaluate safety, pharmacokinetics, pharmacodynamics
      and preliminary efficacy of the investigational drug PLX2853 in subjects with advanced
      malignancies.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.
time frame: First dose of study drug through at least 30 days after end of treatment.
measure: Area under the concentration-time curve (AUC) of PLX2853.
time frame: From first dose of PLX2853 up to 30 days after end of treatment.
measure: Maximum observed concentration (Cmax) of PLX2853.
time frame: From first dose of PLX2853 up to 30 days after end of treatment.
measure: Time to peak concentration (Tmax) of PLX2853.
time frame: From first dose of PLX2853 up to 30 days after end of treatment.
measure: Half life (t1/2) of PLX2853.
time frame: From first dose of PLX2853 up to 30 days after end of treatment.
measure: Number of participants who experience dose limiting toxicity as defined in the protocol.
time frame: Up to 2 years
description: The highest dose level at which less than 2 of 6 participants or less than 33% of participants (if cohort is expanded beyond 6) experience a dose limiting toxicity will be considered the maximum tolerated dose / recommended phase 2 dose.
measure: Change in disease burden using RECIST 1.1 (solid tumors) or Lugano criteria (NHL).
time frame: Up to 2 years
measure: Overall response rate (ORR) defined according to standard criteria for the relevant malignancy [Phase1b]
time frame: From the first dose of study drug until the date of documented response to treatment, assessed up to 2 years.
measure: Duration of response (DOR)
time frame: DOR defined as the time from the initial objective response to disease progression or death, whichever occurs first, assessed up to 2 years.
measure: Progression-Free Survival (PFS)
time frame: PFS time is defined as the time from the first dose of PLX2853 to disease progression or death, whichever occurs first, assessed up to 2 years.
measure: Overall Survival (OS)
time frame: From the first dose of study drug until the date of death from any cause, assessed up to 2 years.
arm group label: PLX2853
arm group type: Experimental
description: Phase 1b (Dose Escalation): Approximately 45 subjects with advanced malignancies to establish the MTD/RP2D. Up to 6 additional subjects may be enrolled at the MTD/RP2D as a dose confirmation.
Phase 2a (Dose Expansion): There will be 5 total expansion cohorts. Either 10 or 29 subjects per cohort in each of 4 expansion cohorts: advanced SCLC, uveal melanoma, OCCC, and any other advanced malignancy with a known ARID1A mutation (between 40 to 116 subjects total for the solid tumor expansion phase). For the 5th expansion cohort, up to 20 subjects may be enrolled for NHL.
intervention type: Drug
intervention name: PLX2853
description: tablets
arm group label: PLX2853
other name: PLX2853 tablets
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Melanoma
mesh term: Neoplasms
mesh term: Lymphoma, Follicular
mesh term: Lymphoma, Non-Hodgkin
mesh term: Lymphoma, B-Cell
mesh term: Small Cell Lung Carcinoma
mesh term: Lymphoma, Large B-Cell, Diffuse
mesh term: Adenomyoepithelioma
mesh term: Adenocarcinoma, Clear Cell