<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/NCT03804996</url>
  </required_header>
  <id_info>
    <org_study_id>TG-1801-101</org_study_id>
    <nct_id>NCT03804996</nct_id>
  </id_info>
  <brief_title>Study of TG-1801 in Subjects With B-Cell Lymphoma</brief_title>
  <official_title>A Phase 1 First-in-Human Study of Bispecific Antibody TG-1801 in Subjects With B-Cell Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>TG Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>TG Therapeutics, Inc.</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Phase 1 first in human Study to Assess the Bispecific Antibody TG-1801 in Subjects with&#xD;
      B-Cell Lymphoma&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label, multi-center, accelerated titration design study. Planned enrollment&#xD;
      includes 1 subject at low dose levels. Subjects will receive weekly infusions of TG-1801 in a&#xD;
      4 week-cycles.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 5, 2019</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2023</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Identification of Recommended Dose</measure>
    <time_frame>18 months of therapy</time_frame>
    <description>To determine the recommended Phase 2 dose (RP2D) by identifying dose limiting toxicity (DLT), maximum tolerable dose (MTD), and optimum biologic dose (OBD).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Characterize the Safety Profile of TG-1801</measure>
    <time_frame>18 months of therapy</time_frame>
    <description>To characterize the safety profile of TG-1801 alone and in combination with ublituximab by evaluating the adverse event profile.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic data collection</measure>
    <time_frame>6 months of therapy</time_frame>
    <description>To evaluate the pharmacokinetics (PK) of TG-1801 including Cmax.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anticancer activity Evaluation</measure>
    <time_frame>6 months of therapy</time_frame>
    <description>To evaluate the preliminary anticancer activity of TG-1801 by evaluating the single-agent arm by assessing the populations of lymphocytes by flow cytometry.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>B-Cell Lymphoma</condition>
  <arm_group>
    <arm_group_label>TG-1801</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm Description: TG-1801 will be administered once every 4 weeks (28-day) cycles. Subjects who experience disease progression after completing 6 months of single agent TG-1801 will be eligible for TG-1801 single-agent re-treatment at the discretion of the investigator.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TG-1101</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm Description: TG-1801 and ublituximab will be administered once every 4 weeks (28-day cycle) for up to 6 cycles followed by TG-1801 monotherapy.&#xD;
To explore the safety of TG-1801 in combination with ublituximab will be explored at doses below and up to the RP2D. TG-1801 intrapatient dose escalation will not be permitted in combination therapy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TG-1801</intervention_name>
    <description>Intravenous infusion over 1 hour every 4 weeks</description>
    <arm_group_label>TG-1101</arm_group_label>
    <arm_group_label>TG-1801</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Ublituximab</intervention_name>
    <description>&quot;recombinant chimeric anti-CD20 monoclonal antibody, available in 25 mg/mL administered as an IV infusion once every 4 weeks&quot;</description>
    <arm_group_label>TG-1101</arm_group_label>
    <other_name>TG-1101</other_name>
    <other_name>LFB-R603</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically confirmed B-cell lymphoma, relapsed to or refractory after at least one&#xD;
             prior standard therapy. For subjects with aggressive lymphoma: those who are&#xD;
             non-candidates for high-dose therapy or autologous stem cell transplant. Refractory is&#xD;
             defined as disease progression during or within 6 months of the most recent prior&#xD;
             therapy, while relapsed is defined as disease progression greater than 6 months after&#xD;
             the most recent prior therapy.&#xD;
&#xD;
          2. Measurable disease defined as at least 1 measurable disease lesion ≥ 1.5 cm in at&#xD;
             least one diameter by CT/CT-PET or magnetic resonance imaging (MRI) in an area of no&#xD;
             prior radiation therapy, or in an area that was previously irradiated that has&#xD;
             documented progression.&#xD;
&#xD;
          3. Be able to provide a core or excisional lymph node biopsy for biomarker analysis from&#xD;
             an archival or newly obtained biopsy at Screening.&#xD;
&#xD;
          4. Adequate organ function defined as:&#xD;
&#xD;
               1. Absolute neutrophil count (ANC) &gt; 1,000/µL and platelet count &gt; 75,000/µL.&#xD;
                  Platelet requirements cannot be met by use of recent transfusion (within 30 days&#xD;
                  of study treatment initiation [Cycle 1 Day 1]). Growth factor support (e.g.&#xD;
                  G-CSF) is not allowed within 2 weeks prior to treatment initiation.&#xD;
&#xD;
               2. Total bilirubin ≤ 1.5 times the ULN, or direct bilirubin ≤ ULN for subjects with&#xD;
                  total bilirubin &gt; 1.5 ULN.&#xD;
&#xD;
               3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN&#xD;
                  if no liver involvement or ≤ 5 x the ULN if known liver involvement.&#xD;
&#xD;
               4. Calculated creatinine (Cr) clearance (CL) &gt; 30 mL/min (as calculated by the&#xD;
                  Cockcroft-Gault or MDRD formula, 24-hour urine Cr CL also acceptable).&#xD;
&#xD;
          5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.&#xD;
&#xD;
          6. Male or female ≥ 18 years of age.&#xD;
&#xD;
          7. Female subjects who are not of child-bearing potential, and female subjects of&#xD;
             child-bearing potential who have a negative serum pregnancy test within 3 days prior&#xD;
             to Cycle 1, Day 1. Female subjects of child-bearing potential, and male partners must&#xD;
             consent to use a medically acceptable method of contraception throughout the study&#xD;
             period and for 4 months after the last administration of ublituximab and 30 days after&#xD;
             last administration of TG-1801. Men of reproductive potential may not participate&#xD;
             unless they agree to use medically acceptable contraception.&#xD;
&#xD;
          8. Willingness and ability to comply with trial and follow-up procedures and provide&#xD;
             written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior therapy with any agent blocking the CD47/SIRPα pathway or any previous CD19&#xD;
             targeting therapy, including but not limited to: antibodies, fragments, bispecific&#xD;
             bodies, or chimeric antigen receptor (CAR) T-cells.&#xD;
&#xD;
          2. Subjects receiving cancer therapy (i.e. chemotherapy, radiation therapy,&#xD;
             immunotherapy, biologic therapy, hormonal therapy, surgery and/or tumor embolization)&#xD;
             or any investigational drug within 21 days of Day 1 of Cycle 1 (42 days for prior&#xD;
             mitomycin C or a nitrosourea).&#xD;
&#xD;
             a. Corticosteroid therapy started at least 7 days prior to Cycle 1 Day 1 (prednisone ≤&#xD;
             10 mg daily or equivalent) is allowed as clinically warranted. Topical or inhaled&#xD;
             corticosteroids are permitted.&#xD;
&#xD;
          3. Prior autologous stem cell transplant within 6 months. Prior allogeneic hematologic&#xD;
             stem cell transplant within 1 year and excluded if there is active graft versus host&#xD;
             disease.&#xD;
&#xD;
          4. Subjects who have not recovered (≤ Grade 1 or at baseline) from adverse events due to&#xD;
             previous therapy, except for alopecia and Grade 2 neuropathy due to previous cancer&#xD;
             therapy.&#xD;
&#xD;
             Note: Toxicity that has not recovered to ≤ Grade 1 is allowed if it meets the&#xD;
             inclusion requirements for laboratory parameters defined above.&#xD;
&#xD;
          5. Any severe or uncontrolled illness or other conditions that could affect their&#xD;
             participation in the study including, but not limited to:&#xD;
&#xD;
               1. Symptomatic, or history of documented congestive heart failure (NY Heart&#xD;
                  Association functional classification III-IV).&#xD;
&#xD;
               2. Myocardial infarction within 6 months of enrollment.&#xD;
&#xD;
               3. Poorly controlled or clinically significant atherosclerotic vascular disease&#xD;
                  including cerebrovascular accident, transient ischemic attack, angioplasty,&#xD;
                  cardiac/vascular stenting within 6 months of enrollment, angina not well&#xD;
                  controlled by medication.&#xD;
&#xD;
               4. Ongoing or active infection, except localized fungal infection of skin or nails.&#xD;
&#xD;
          6. Known active Hepatitis B (e.g. HBsAg reactive), Hepatitis C (e.g. HCV RNA&#xD;
             [qualitative] is detected), cytomegalovirus (CMV DNA by PCR), or known history of HIV.&#xD;
&#xD;
          7. Malignancy within 2 years of study enrollment except for adequately treated basal or&#xD;
             squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast,&#xD;
             superficial bladder cancer, or localized prostate cancer.&#xD;
&#xD;
          8. Known clinically active CNS involvement.&#xD;
&#xD;
          9. History of anaphylaxis or severe allergy to a monoclonal antibody; or known or&#xD;
             suspected hypersensitivity to the excipients contained in the study drug formulation.&#xD;
&#xD;
         10. Lactating or pregnant.&#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>TG Therapeutics Investigational Trial Site</name>
      <address>
        <city>Heidelberg</city>
        <state>Victoria</state>
        <zip>03084</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TG Therapeutics Investigational Trial Site</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TG Therapeutics Investigational Trial Site</name>
      <address>
        <city>Nedlands</city>
        <state>Western Australia</state>
        <zip>06009</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>January 12, 2019</study_first_submitted>
  <study_first_submitted_qc>January 12, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 15, 2019</study_first_posted>
  <last_update_submitted>August 17, 2023</last_update_submitted>
  <last_update_submitted_qc>August 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 21, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>relapsed or refractory</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, B-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/NCT03804996
org study id: TG-1801-101
nct id: NCT03804996
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Phase 1 first in human Study to Assess the Bispecific Antibody TG-1801 in Subjects with
      B-Cell Lymphoma
This is an open-label, multi-center, accelerated titration design study. Planned enrollment
      includes 1 subject at low dose levels. Subjects will receive weekly infusions of TG-1801 in a
      4 week-cycles.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Identification of Recommended Dose
time frame: 18 months of therapy
description: To determine the recommended Phase 2 dose (RP2D) by identifying dose limiting toxicity (DLT), maximum tolerable dose (MTD), and optimum biologic dose (OBD).
measure: Characterize the Safety Profile of TG-1801
time frame: 18 months of therapy
description: To characterize the safety profile of TG-1801 alone and in combination with ublituximab by evaluating the adverse event profile.
measure: Pharmacokinetic data collection
time frame: 6 months of therapy
description: To evaluate the pharmacokinetics (PK) of TG-1801 including Cmax.
measure: Anticancer activity Evaluation
time frame: 6 months of therapy
description: To evaluate the preliminary anticancer activity of TG-1801 by evaluating the single-agent arm by assessing the populations of lymphocytes by flow cytometry.
arm group label: TG-1801
arm group type: Experimental
description: Arm Description: TG-1801 will be administered once every 4 weeks (28-day) cycles. Subjects who experience disease progression after completing 6 months of single agent TG-1801 will be eligible for TG-1801 single-agent re-treatment at the discretion of the investigator.
arm group label: TG-1101
arm group type: Experimental
description: Arm Description: TG-1801 and ublituximab will be administered once every 4 weeks (28-day cycle) for up to 6 cycles followed by TG-1801 monotherapy.
To explore the safety of TG-1801 in combination with ublituximab will be explored at doses below and up to the RP2D. TG-1801 intrapatient dose escalation will not be permitted in combination therapy.
intervention type: Drug
intervention name: TG-1801
description: Intravenous infusion over 1 hour every 4 weeks
arm group label: TG-1101
arm group label: TG-1801
intervention type: Biological
intervention name: Ublituximab
description: "recombinant chimeric anti-CD20 monoclonal antibody, available in 25 mg/mL administered as an IV infusion once every 4 weeks"
arm group label: TG-1101
other name: TG-1101
other name: LFB-R603
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
country: Australia
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, B-Cell