<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/NCT03027128</url>
  </required_header>
  <id_info>
    <org_study_id>QUILT-3.028</org_study_id>
    <nct_id>NCT03027128</nct_id>
  </id_info>
  <brief_title>QUILT-3.028: Study of haNK™ for Infusion in Subjects With Metastatic or Locally Advanced Solid Tumors</brief_title>
  <official_title>Open-label, Phase 1 Study of haNK™ for Infusion in Subjects With Metastatic or Locally Advanced Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>ImmunityBio, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>ImmunityBio, 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 determine whether haNK™ for Infusion is safe and effective in&#xD;
      the treatment of metastatic or locally advanced solid tumors.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a phase 1 trial in subjects with metastatic or locally advanced solid tumors. The&#xD;
      study will be conducted in two parts: part 1 will involve dose escalation using a 3 + 3&#xD;
      design, and part 2 will involve the expansion of the MTD or HTD to further evaluate the&#xD;
      safety of haNK. In part 1, 3 to 6 subjects will be sequentially enrolled starting at dose&#xD;
      cohort 1, and subjects will be assessed for DLTs.&#xD;
&#xD;
        -  Cohort 1: 2 x 10^9 cells per infusion.&#xD;
&#xD;
        -  Cohort 2: 4 x 10^9 cells per infusion.&#xD;
&#xD;
        -  If needed, subjects will be enrolled into a dose de-escalation cohort (cohort -1): 1 x&#xD;
           10^9 cells per infusion.&#xD;
&#xD;
      In part 2, dose expansion will occur when the MTD or HTD has been determined. An additional 4&#xD;
      subjects may be enrolled in part 2, for a total of up to 10 subjects at the MTD or HTD.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 2, 2017</start_date>
  <completion_date type="Actual">February 7, 2019</completion_date>
  <primary_completion_date type="Actual">February 7, 2019</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>Determination of maximum tolerated dose (MTD) or highest tested dose (HTD).</measure>
    <time_frame>2 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurrence of dose-limiting toxicities (DLTs).</measure>
    <time_frame>2 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurrence of treatment-emergent adverse event (AEs) and serious adverse events (SAEs).</measure>
    <time_frame>2 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and immune-related response criteria (irRC).</measure>
    <time_frame>2 years</time_frame>
    <description>ORR is defined as the proportion of patients with a confirmed complete or partial response.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS) by RECIST and irRC.</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS).</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Solid Tumor</condition>
  <arm_group>
    <arm_group_label>haNK™ for Infusion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>NK-92 [CD16.158V, ER IL-2], Suspension for Intravenous Infusion</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>haNK™ for Infusion</intervention_name>
    <description>haNK™ for Infusion is a human, allogeneic, NK cell line that has been engineered to produce endogenous, intracellularly retained IL-2 and to express CD16, the high-affinity (158V) Fc gamma receptor (FcγRIIIa/CD16a).</description>
    <arm_group_label>haNK™ for Infusion</arm_group_label>
    <other_name>NK-92 [CD16.158V, ER IL-2], Suspension for Intravenous</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥ 18 years old.&#xD;
&#xD;
          2. Able to understand and provide a signed informed consent that fulfills the relevant&#xD;
             IRB or IEC guidelines.&#xD;
&#xD;
          3. Histologically confirmed, unresectable, locally advanced or metastatic solid&#xD;
             malignancy.&#xD;
&#xD;
          4. ECOG performance status of 0 to 2.&#xD;
&#xD;
          5. Have at least 1 measurable lesion and/or non-measurable disease evaluable according to&#xD;
             RECIST Version 1.1.&#xD;
&#xD;
          6. Must have a recent formalin-fixed, paraffin-embedded (FFPE) tumor biopsy specimen&#xD;
             following the conclusion of the most recent anticancer treatment. If an historic&#xD;
             specimen is not available, the subject must be willing to undergo a biopsy during the&#xD;
             screening period, if considered safe by the Investigator. If safety concerns preclude&#xD;
             collection of a biopsy during the screening period, a tumor biopsy specimen collected&#xD;
             prior to the conclusion of the most recent anticancer treatment may be used.&#xD;
&#xD;
          7. Must be willing to provide pre- and post-infusion blood samples.&#xD;
&#xD;
          8. Have received treatment with at least 1 prior line of therapy in the metastatic&#xD;
             setting or not be a candidate for therapy of proven efficacy for their disease. Prior&#xD;
             immune therapy is allowed.&#xD;
&#xD;
          9. Resolution of all toxic side effects of prior chemotherapy, radiotherapy, or surgical&#xD;
             procedures to CTCAE grade ≤ 1, with the exception of alopecia.&#xD;
&#xD;
         10. Life expectancy ≥ 12 weeks.&#xD;
&#xD;
         11. Ability to attend required study visits and return for adequate follow-up, as required&#xD;
             by this protocol.&#xD;
&#xD;
         12. Agreement to practice effective contraception for female subjects of child-bearing&#xD;
             potential and non-sterile males. Female subjects of child-bearing potential are&#xD;
             considered all female subjects being physiologically capable of becoming pregnant.&#xD;
             Female subjects of child-bearing potential are usually premenopausal women or women&#xD;
             with less than 12 months of amenorrhea post-menopause and who have not undergone&#xD;
             surgical sterilization. Female subjects of child-bearing potential and non-sterile&#xD;
             male subjects must agree to use effective contraception for at least 60 days (female)&#xD;
             and 120 days (male) after the last dose of haNK. Effective contraception includes&#xD;
             surgical sterilization (eg, vasectomy, tubal ligation), two forms of barrier methods&#xD;
             (eg, condom, diaphragm) used with spermicide, intrauterine devices (IUDs), and&#xD;
             abstinence.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of persistent grade 2 or higher (CTCAE Version 4.03) hematological toxicity&#xD;
             resulting from previous therapy.&#xD;
&#xD;
          2. Serious uncontrolled concomitant disease that would contraindicate the use of the&#xD;
             investigational drug used in this study or that would put the subject at high risk for&#xD;
             treatment-related complications.&#xD;
&#xD;
          3. Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's&#xD;
             disease, autoimmune disease associated with lymphoma).&#xD;
&#xD;
          4. History of organ transplant requiring immunosuppression.&#xD;
&#xD;
          5. History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative&#xD;
             colitis).&#xD;
&#xD;
          6. Inadequate organ function, evidenced by the following laboratory results:&#xD;
&#xD;
               -  White blood cell (WBC) count &lt; 2,500 cells/mm^3&#xD;
&#xD;
               -  Absolute neutrophil count &lt; 1,500 cells/mm^3.&#xD;
&#xD;
               -  Platelet count &lt; 100,000 cells/mm3.&#xD;
&#xD;
               -  Hemoglobin &lt; 9 g/dL.&#xD;
&#xD;
               -  Total bilirubin greater than the upper limit of normal (ULN; unless the subject&#xD;
                  has documented Gilbert's syndrome).&#xD;
&#xD;
               -  Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT])&#xD;
                  &gt; 2.5 × ULN (&gt; 5 × ULN in subjects with liver metastases).&#xD;
&#xD;
               -  Alkaline phosphatase levels &gt; 2.5 × ULN (&gt; 5 × ULN in subjects with liver&#xD;
                  metastases, or &gt;10 × ULN in subjects with bone metastases).&#xD;
&#xD;
               -  Serum creatinine &gt; 2.0 mg/dL or 177 μmol/L.&#xD;
&#xD;
          7. Uncontrolled hypertension (systolic &gt; 150 mm Hg and/or diastolic &gt; 100 mm Hg) or&#xD;
             clinically significant (ie, active) cardiovascular disease, cerebrovascular&#xD;
             accident/stroke, or myocardial infarction within 6 months prior to first study&#xD;
             medication; unstable angina; congestive heart failure of New York Heart Association&#xD;
             grade 2 or higher; or serious cardiac arrhythmia requiring medication.&#xD;
&#xD;
          8. Dyspnea at rest due to complications of advanced malignancy or other disease requiring&#xD;
             continuous oxygen therapy.&#xD;
&#xD;
          9. Positive results of screening test for human immunodeficiency virus (HIV). However,&#xD;
             subjects with HIV are allowed on the study if they meet the following criteria:&#xD;
&#xD;
               -  CD4+ T-cell count &gt;200 cells/mm^3.&#xD;
&#xD;
               -  Stable antiretrovital therapy for at least 12 weeks prior to entry.&#xD;
&#xD;
               -  Plasma HIV RNA levels below lower limit of quantification at screening, and no&#xD;
                  quantifiable HIV RNA levels within the 12 weeks preceding screening.&#xD;
&#xD;
         10. Current chronic daily treatment (continuous for &gt; 3 months) with systemic&#xD;
             corticosteroids (dose equivalent to or greater than 10 mg/day methylprednisolone),&#xD;
             excluding inhaled steroids. Short-term steroid use to prevent IV contrast allergic&#xD;
             reaction or anaphylaxis in subjects who have known contrast allergies is allowed.&#xD;
&#xD;
         11. Known hypersensitivity to any component of the study medication(s).&#xD;
&#xD;
         12. Participation in an investigational drug study or history of receiving any&#xD;
             investigational treatment within 28 days prior to screening for this study, except for&#xD;
             testosterone-lowering therapy in men with prostate cancer.&#xD;
&#xD;
         13. Assessed by the Investigator to be unable or unwilling to comply with the requirements&#xD;
             of the protocol.&#xD;
&#xD;
         14. Concurrent participation in any interventional clinical trial.&#xD;
&#xD;
         15. Pregnant and nursing women. A negative serum pregnancy test within 72 hours before&#xD;
             administration of haNK must be documented before any haNK is administered to a female&#xD;
             subject of child-bear potential.&#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>Chan Soon-Shiong Institute for Medicine</name>
      <address>
        <city>El Segundo</city>
        <state>California</state>
        <zip>90245</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>January 18, 2017</study_first_submitted>
  <study_first_submitted_qc>January 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 20, 2017</study_first_posted>
  <last_update_submitted>August 23, 2019</last_update_submitted>
  <last_update_submitted_qc>August 23, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 28, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Phase 1</keyword>
  <keyword>Metastatic</keyword>
  <keyword>Locally Advanced</keyword>
  <keyword>Cancer</keyword>
  <keyword>Cell Therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03027128
org study id: QUILT-3.028
nct id: NCT03027128
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to determine whether haNK™ for Infusion is safe and effective in
      the treatment of metastatic or locally advanced solid tumors.
This is a phase 1 trial in subjects with metastatic or locally advanced solid tumors. The
      study will be conducted in two parts: part 1 will involve dose escalation using a 3 + 3
      design, and part 2 will involve the expansion of the MTD or HTD to further evaluate the
      safety of haNK. In part 1, 3 to 6 subjects will be sequentially enrolled starting at dose
      cohort 1, and subjects will be assessed for DLTs.

        -  Cohort 1: 2 x 10^9 cells per infusion.

        -  Cohort 2: 4 x 10^9 cells per infusion.

        -  If needed, subjects will be enrolled into a dose de-escalation cohort (cohort -1): 1 x
           10^9 cells per infusion.

      In part 2, dose expansion will occur when the MTD or HTD has been determined. An additional 4
      subjects may be enrolled in part 2, for a total of up to 10 subjects at the MTD or HTD.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Determination of maximum tolerated dose (MTD) or highest tested dose (HTD).
time frame: 2 years
measure: Occurrence of dose-limiting toxicities (DLTs).
time frame: 2 years
measure: Occurrence of treatment-emergent adverse event (AEs) and serious adverse events (SAEs).
time frame: 2 years
measure: Objective response rate (ORR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and immune-related response criteria (irRC).
time frame: 2 years
description: ORR is defined as the proportion of patients with a confirmed complete or partial response.
measure: Progression free survival (PFS) by RECIST and irRC.
time frame: 2 years
measure: Overall survival (OS).
time frame: 2 years
arm group label: haNK™ for Infusion
arm group type: Experimental
description: NK-92 [CD16.158V, ER IL-2], Suspension for Intravenous Infusion
intervention type: Biological
intervention name: haNK™ for Infusion
description: haNK™ for Infusion is a human, allogeneic, NK cell line that has been engineered to produce endogenous, intracellularly retained IL-2 and to express CD16, the high-affinity (158V) Fc gamma receptor (FcγRIIIa/CD16a).
arm group label: haNK™ for Infusion
other name: NK-92 [CD16.158V, ER IL-2], Suspension for Intravenous
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
sharing ipd: No