<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/NCT03819387</url>
  </required_header>
  <id_info>
    <org_study_id>NBF-006-001</org_study_id>
    <nct_id>NCT03819387</nct_id>
  </id_info>
  <brief_title>A Study of NBF-006 in Non-Small Cell Lung, Pancreatic, or Colorectal Cancer</brief_title>
  <official_title>A Phase I/Ib Open-Label, Multi-Center, Dose-Escalation Study to Investigate the Safety, Pharmacokinetics and Preliminary Efficacy of Intravenous NBF 006 in Patients With Non-Small Cell Lung, Pancreatic, or Colorectal Cancer Followed by a Dose Expansion Study in Patients With KRAS-Mutated Non-Small Cell Lung Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nitto BioPharma, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Nitto BioPharma, 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>
      This is an open-label, non-controlled study conducted in two parts - Part A (dose escalation)&#xD;
      followed by Part B (dose expansion).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients in Part A will have previously treated progressive or metastatic NSCLC, pancreatic,&#xD;
      or colorectal cancer, with or without KRAS mutation. Five dose levels will be explored. In&#xD;
      dose level 5, only patients with previously-treated NSCLC with KRAS mutation will be&#xD;
      included.&#xD;
&#xD;
      Patients in Part B must have previously treated NSCLC with confirmed KRAS mutation. Two dose&#xD;
      levels will be explored further in Part B. Twenty (20) patients will be enrolled in Part B,&#xD;
      with 10 patients enrolled in each of the two cohorts. Once dose level 5 has been confirmed to&#xD;
      be safe in Part A (i.e. 0-1 DLT in 6 patients), an additional 4 patients will then be&#xD;
      enrolled for a planned total of 24 patients in Part B.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 18, 2019</start_date>
  <completion_date type="Anticipated">August 2024</completion_date>
  <primary_completion_date type="Anticipated">March 2024</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 patients with treatment-related adverse events as assessed by CTCAE v5.0</measure>
    <time_frame>Change in the incidence and severity of adverse events related to study treatment from baseline to 4 weeks following last dose</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Best Overall Response per RECIST 1.1</measure>
    <time_frame>Number of days from date of first dose to 30 days after last treatment</time_frame>
    <description>The rate of complete remission (CR) + partial remission (PR) + stable disease (SD)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic parameters for siRNA</measure>
    <time_frame>Up to 72 hours from start of infusion on Cycle 1, Day 1 and Day 22 and prior to infusion Cycle 1, Day 8 and Cycle 2, Day 1</time_frame>
    <description>Peak Plasma Concentration (Cmax)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Additional pharmacokinetic parameters for siRNA</measure>
    <time_frame>Up to 72 hours from start of infusion on Cycle 1, Day 1 and Day 22 and prior to infusion Cycle 1, Day 8 and Cycle 2, Day 1</time_frame>
    <description>Area under the plasma concentration versus time curve (AUC)</description>
  </secondary_outcome>
  <other_outcome>
    <measure>To evaluate correlation between biomarkers and clinical outcome</measure>
    <time_frame>Number of days from date of first dose to 30 days after last treatment</time_frame>
    <description>analysis of ADAs, immune activation biomarkers, GSTP knockdown, and other biomarker activity</description>
  </other_outcome>
  <other_outcome>
    <measure>To evaluate correlation between KRAS mutations and clinical outcome</measure>
    <time_frame>Number of days from date of first dose to 30 days after last treatment</time_frame>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">44</enrollment>
  <condition>Non-Small Cell Lung Cancer</condition>
  <condition>Pancreatic Cancer</condition>
  <condition>Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>NBF-006</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NBF-006</intervention_name>
    <description>Intravenous infusion, once-weekly x 4 consecutive weeks, every 6 weeks</description>
    <arm_group_label>NBF-006</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Part A: Patients with histologically or cytologically confirmed progressive or&#xD;
             metastatic NSCLC, pancreatic, or colorectal cancer that have failed standard treatment&#xD;
             and for which no other effective treatment is available or appropriate for the patient&#xD;
             up to dose level 4. In dose level 5, patients with histologically or cytologically&#xD;
             confirmed progressive or metastatic NSCLC with documented KRAS-mutant genotype, who&#xD;
             have failed standard treatment and have no other effective treatment available or&#xD;
             appropriate for the patient.&#xD;
&#xD;
             Part B: Patients with histologically or cytologically confirmed progressive or&#xD;
             metastatic NSCLC with documented KRAS-mutant genotype, who have failed standard&#xD;
             treatment and have no other effective treatment available or appropriate for the&#xD;
             patient.&#xD;
&#xD;
          2. Eastern Cooperative Oncology Group performance status of 0-2.&#xD;
&#xD;
          3. Men and women ≥ 18 years of age.&#xD;
&#xD;
          4. Patients must have recovered from all acute adverse effects (excluding alopecia) of&#xD;
             prior therapies to baseline or ≤ Grade 1 prior to study entry.&#xD;
&#xD;
          5. Adequate bone marrow function, defined as an absolute neutrophil count (ANC) ≥ 1.5 x&#xD;
             109/L and a platelet count ≥ 100 x 109/L.&#xD;
&#xD;
          6. Adequate renal function, defined as serum creatinine ≤ 1.5 x upper limit of normal&#xD;
             (ULN) for the institution or calculated creatinine clearance [Cockcroft-Gault method]&#xD;
             must be ≥ 60 mL/min/1.73 m². If serum creatinine is &gt;1.5 x ULN, then creatinine&#xD;
             clearance can be calculated from a 24-hour urine collection.&#xD;
&#xD;
          7. Adequate hepatic function, defined as total bilirubin ≤ 1.5 mg/dL and alanine&#xD;
             transaminase (ALT) and aspartate transaminase (AST) ≤ 2.5 x ULN, or ≤ 5 x ULN if known&#xD;
             liver metastases.&#xD;
&#xD;
          8. Female patients of childbearing potential must have a negative serum or urine&#xD;
             pregnancy test result at time of pre-treatment screening.&#xD;
&#xD;
          9. Patients with reproductive potential must agree to use at least one form of highly&#xD;
             effective contraception prior to study entry and for up to 30 days beyond the last&#xD;
             administration of study drug.&#xD;
&#xD;
         10. Patients must be capable of providing informed consent and must be willing to provide&#xD;
             written informed consent prior to the start of any study-specific procedures.&#xD;
&#xD;
         11. All patients must have measurable tumor per RECIST 1.1.&#xD;
&#xD;
         12. Agree to adhere to all study protocol requirements.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior chemotherapy, radiation therapy, or investigational therapy within 4 weeks&#xD;
             (exception: 6 weeks for nitrosoureas or mitomycin C); or prior non-cytotoxic therapy&#xD;
             within 5 drug half-lives (or 4 weeks, whichever is shorter); or monoclonal antibodies&#xD;
             within 4 weeks prior to the first dose of study treatment.&#xD;
&#xD;
          2. Concurrent use of any other investigational agent.&#xD;
&#xD;
          3. Known or clinically suspected central nervous system or leptomeningeal metastases,&#xD;
             unless irradiated or treated a minimum of 4 weeks prior to first study treatment and&#xD;
             stable without requirement of corticosteroids for &gt; 1 week.&#xD;
&#xD;
          4. Pregnant or breast feeding. A negative pregnancy test must be documented at baseline&#xD;
             for women of childbearing potential. Patients may not breast-feed infants while on&#xD;
             this study.&#xD;
&#xD;
          5. Significant cardiovascular disease or condition, including:&#xD;
&#xD;
               1. Congestive heart failure currently requiring therapy&#xD;
&#xD;
               2. Need for antiarrhythmic medical therapy for ventricular arrhythmia&#xD;
&#xD;
               3. Severe conduction disturbance&#xD;
&#xD;
               4. Angina pectoris requiring therapy&#xD;
&#xD;
               5. QTc interval &gt; 450 msec (males) or &gt; 470 msec (females) Fridericia's correction.&#xD;
&#xD;
                  Note: QTc values up to 500 ms will be acceptable where patient's medical history&#xD;
                  e.g. bundle branch block, is known to cause mild QTc prolongation and the&#xD;
                  condition is well controlled.&#xD;
&#xD;
               6. History of congenital long QT syndrome or congenital short QT syndrome&#xD;
&#xD;
               7. Uncontrolled hypertension (per the Investigator's discretion)&#xD;
&#xD;
               8. Class III or IV cardiovascular disease according to the New York Heart&#xD;
                  Association's Functional Criteria&#xD;
&#xD;
               9. Myocardial infarction within 6 months prior to first study drug administration&#xD;
&#xD;
          6. Known history of human immunodeficiency virus or active infection with hepatitis B&#xD;
             virus or hepatitis C virus.&#xD;
&#xD;
          7. Known uncontrolled intercurrent illnesses, including uncontrolled viral influenza and&#xD;
             COVID 19, systemic bacterial infections, and fungal infections.&#xD;
&#xD;
          8. Psychiatric disorder or altered mental status that would preclude understanding of the&#xD;
             informed consent process and/or completion of the necessary studies.&#xD;
&#xD;
          9. Known allergic reactions to H1/H2 antagonists.&#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>Beverly Hills Cancer Center</name>
      <address>
        <city>Beverly Hills</city>
        <state>California</state>
        <zip>90211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UC San Diego Moores Cancer Center</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Moffitt Cancer Center</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Toledo, Eleanor N. Dana Cancer Center</name>
      <address>
        <city>Toledo</city>
        <state>Ohio</state>
        <zip>43614</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt-Ingram Cancer Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NEXT Oncology - Austin</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78758</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mary Crowley Cancer Research Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75230</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NEXT Oncology - San Antonio</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78240</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NEXT Oncology - Virginia</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>August 2023</verification_date>
  <study_first_submitted>January 25, 2019</study_first_submitted>
  <study_first_submitted_qc>January 25, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <last_update_submitted>August 30, 2023</last_update_submitted>
  <last_update_submitted_qc>August 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 31, 2023</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>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
    <mesh_term>Colorectal Neoplasms</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/NCT03819387
org study id: NBF-006-001
nct id: NCT03819387
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is an open-label, non-controlled study conducted in two parts - Part A (dose escalation)
      followed by Part B (dose expansion).
Patients in Part A will have previously treated progressive or metastatic NSCLC, pancreatic,
      or colorectal cancer, with or without KRAS mutation. Five dose levels will be explored. In
      dose level 5, only patients with previously-treated NSCLC with KRAS mutation will be
      included.

      Patients in Part B must have previously treated NSCLC with confirmed KRAS mutation. Two dose
      levels will be explored further in Part B. Twenty (20) patients will be enrolled in Part B,
      with 10 patients enrolled in each of the two cohorts. Once dose level 5 has been confirmed to
      be safe in Part A (i.e. 0-1 DLT in 6 patients), an additional 4 patients will then be
      enrolled for a planned total of 24 patients in Part B.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of patients with treatment-related adverse events as assessed by CTCAE v5.0
time frame: Change in the incidence and severity of adverse events related to study treatment from baseline to 4 weeks following last dose
measure: Best Overall Response per RECIST 1.1
time frame: Number of days from date of first dose to 30 days after last treatment
description: The rate of complete remission (CR) + partial remission (PR) + stable disease (SD)
measure: Pharmacokinetic parameters for siRNA
time frame: Up to 72 hours from start of infusion on Cycle 1, Day 1 and Day 22 and prior to infusion Cycle 1, Day 8 and Cycle 2, Day 1
description: Peak Plasma Concentration (Cmax)
measure: Additional pharmacokinetic parameters for siRNA
time frame: Up to 72 hours from start of infusion on Cycle 1, Day 1 and Day 22 and prior to infusion Cycle 1, Day 8 and Cycle 2, Day 1
description: Area under the plasma concentration versus time curve (AUC)
measure: To evaluate correlation between biomarkers and clinical outcome
time frame: Number of days from date of first dose to 30 days after last treatment
description: analysis of ADAs, immune activation biomarkers, GSTP knockdown, and other biomarker activity
measure: To evaluate correlation between KRAS mutations and clinical outcome
time frame: Number of days from date of first dose to 30 days after last treatment
arm group label: NBF-006
arm group type: Experimental
intervention type: Drug
intervention name: NBF-006
description: Intravenous infusion, once-weekly x 4 consecutive weeks, every 6 weeks
arm group label: NBF-006
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Colorectal Neoplasms