<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/NCT04464967</url>
  </required_header>
  <id_info>
    <org_study_id>SNK01-102</org_study_id>
    <nct_id>NCT04464967</nct_id>
  </id_info>
  <brief_title>Safety and Preliminary Efficacy of SNK01 in Combination With Trastuzumab or Cetuximab in Subjects With Advanced HER2 or EGFR Cancers</brief_title>
  <official_title>A Phase 1/2a, Open-Label, Multi-Center Study Evaluating the Safety and Anti-Tumor Activity of Ex Vivo Expanded, Autologous Natural Killer Cells (SNK01) in Combination With Trastuzumab or Cetuximab in Subjects With Advanced/Metastatic HER2- or EGFR-Expressing Cancers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NKGen Biotech, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>NKGen Biotech, Inc.</source>
  <oversight_info>
    <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 the Phase 1/2a study is to evaluate the safety and tolerability of SNK01 in&#xD;
      combination with trastuzumab or cetuximab in order to determine the maximum tolerated dose&#xD;
      (MTD)/recommended Phase 2 dose (RP2D), and the preliminary efficacy for each combination&#xD;
      regimen.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Trial not initiated&#xD;
  </why_stopped>
  <start_date type="Anticipated">March 2021</start_date>
  <completion_date type="Anticipated">February 2023</completion_date>
  <primary_completion_date type="Anticipated">August 2022</primary_completion_date>
  <phase>Phase 1/Phase 2</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>Phase 1 - To determine recommended Phase 2 dose (RP2D) of SNK01 in combination with trastuzumab in subjects with advanced HER2 cancers.</measure>
    <time_frame>Up to 6 months</time_frame>
    <description>Evaluated by the number of DLTs graded using NCI CTCAE v5.0.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 1 - To determine recommended Phase 2 dose (RP2D) of SNK01 in combination with cetuximab in subjects with advanced EGFR cancers.</measure>
    <time_frame>Up to 6 months</time_frame>
    <description>Evaluated by the number of DLTs graded using NCI CTCAE v5.0.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 2a - To assess objective response rate (ORR) of SNK01 in combination with trastuzumab in subjects with advanced HER2 cancers.</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Defined by percentage of subjects with a best response of complete response (CR), partial response (PR) or stable disease (SD) by investigator assessment per RECIST 1.1.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 2a - To assess objective response rate (ORR) of SNK01 in combination with cetuximab in subjects with advanced EGFR cancers.</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Defined by percentage of subjects with a best response of complete response (CR), partial response (PR) or stable disease (SD) by investigator assessment per RECIST 1.1.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Phase 2a - To assess the progression-free survival (PFS) of SNK01 in combination with trastuzumab in subjects with advanced HER2 cancers.</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Defined by the time of the date of first dose of study drug until confirmed disease progression based on investigator assessment per RECIST 1.1 or death from any cause, whichever comes first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2a - To assess the progression-free survival (PFS) of SNK01 in combination with cetuximab in subjects with advanced EGFR cancers.</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Defined by the time of the date of first dose of study drug until confirmed disease progression based on investigator assessment per RECIST 1.1 or death from any cause, whichever comes first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2a - To assess the overall survival (OS) of SNK01 in combination with trastuzumab in subjects with advanced HER2 cancers.</measure>
    <time_frame>Up to 24 months</time_frame>
    <description>Defined as time from first dose of study drug to death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2a - To assess the overall survival (OS) of SNK01 in combination with cetuximab in subjects with advanced EGFR cancers.</measure>
    <time_frame>Up to 24 months</time_frame>
    <description>Defined as time from first dose of study drug to death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2a - To assess the duration of response (DOR) of SNK01 in combination with trastuzumab in subjects with advanced HER2 cancers.</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Defined as duration of time from initial response (complete response [CR] or partial response [PR]) to first documentation of disease progression or death from any cause, whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2a - To assess the duration of response (DOR) of SNK01 in combination with cetuximab in subjects with advanced EGFR cancers.</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Defined as duration of time from initial response (complete response [CR] or partial response [PR]) to first documentation of disease progression or death from any cause, whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2a - To assess the clinical benefit rate (CBR) of SNK01 in combination with trastuzumab in subjects with advanced HER2 cancers.</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Defined as proportion of subjects who achieve an overall tumor response (complete response [CR] or partial response [PR] or stable disease [SD]).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2a - To assess the clinical benefit rate (CBR) of SNK01 in combination with cetuximab in subjects with advanced EGFR cancers.</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Defined as proportion of subjects who achieve an overall tumor response (complete response [CR] or partial response [PR] or stable disease [SD]).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2a - Impact of SNK01 in combination with trastuzumab on quality of life in subjects with advanced HER2 cancers evaluated using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30).</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>The EORTC QLQ-C30 questionnaire consists of 30 questions, 24 of which are grouped into nine multi-item scales (five functioning scales [physical, role, cognitive, emotional and social], three symptom scales [fatigue, pain and nausea/vomiting] and one global health status scale). The remaining six questions are single-item scales (dyspnea, appetite loss, sleep disturbance, constipation, diarrhea and the financial impact) and are intended to assess symptoms.&#xD;
All of the scales and single-item measures are scored on a scale from 0 to 100. A better state of the patient is denoted by a higher score for the functioning scales and global health status, while a worsening state of the patient is denoted by higher scores on the symptom and single-item scales.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2a - Impact of SNK01 in combination with cetuximab on quality of life in subjects with advanced EGFR cancers evaluated using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30).</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>The EORTC QLQ-C30 questionnaire consists of 30 questions, 24 of which are grouped into nine multi-item scales (five functioning scales [physical, role, cognitive, emotional and social], three symptom scales [fatigue, pain and nausea/vomiting] and one global health status scale). The remaining six questions are single-item scales (dyspnea, appetite loss, sleep disturbance, constipation, diarrhea and the financial impact) and are intended to assess symptoms.&#xD;
All of the scales and single-item measures are scored on a scale from 0 to 100. A better state of the patient is denoted by a higher score for the functioning scales and global health status, while a worsening state of the patient is denoted by higher scores on the symptom and single-item scales.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2a-Impact of SNK01 in combination with trastuzumab on quality of life in subjects with advanced HER2 cancers evaluated using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer 13 (QLQ-LC13).</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>The EORTC QLQ-LC13 is a supplementary lung-cancer specific questionnaire and is used in conjunction with the EORTC QLQ-C30 questionnaire. It is comprised of 13 questions, 3 of which are grouped into a multi-item scale to assess dyspnea and 10 of which are single-item scales assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis.&#xD;
All of the scales and single-item measures are scored on a scale from 0 to 100. A better state of the patient is denoted by a higher score for the functioning scales and global health status, while a worsening state of the patient is denoted by higher scores on the symptom and single-item scales.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2a - Impact of SNK01 in combination with cetuximab on quality of life in subjects with advanced EGFR cancers evaluated using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer 13 (QLQ-LC13).</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>The EORTC QLQ-LC13 is a supplementary lung-cancer specific questionnaire and is used in conjunction with the EORTC QLQ-C30 questionnaire. It is comprised of 13 questions, 3 of which are grouped into a multi-item scale to assess dyspnea and 10 of which are single-item scales assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis.&#xD;
All of the scales and single-item measures are scored on a scale from 0 to 100. A better state of the patient is denoted by a higher score for the functioning scales and global health status, while a worsening state of the patient is denoted by higher scores on the symptom and single-item scales.</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Advanced Solid Tumor</condition>
  <condition>Metastatic Cancer</condition>
  <condition>HER2-positive Breast Cancer</condition>
  <condition>HER2-positive Gastric Cancer</condition>
  <condition>HER-2 Protein Overexpression</condition>
  <condition>Esophageal Cancer</condition>
  <condition>Ovarian Cancer</condition>
  <condition>Endometrium Cancer</condition>
  <condition>Bladder Cancer</condition>
  <condition>Pancreatic Cancer</condition>
  <condition>Colorectal Cancer</condition>
  <condition>Non Small Cell Lung Cancer</condition>
  <condition>EGF-R Positive Non-Small Cell Lung Cancer</condition>
  <condition>Head and Neck Squamous Cell Carcinoma</condition>
  <condition>Triple Negative Breast Cancer</condition>
  <condition>Cervical Cancer</condition>
  <condition>Sarcoma</condition>
  <arm_group>
    <arm_group_label>Phase 1, Cohort 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SNK01 (low dose) administered once every three weeks in combination with trastuzumab (loading dose of 8 mg/kg on Cycle 1, Day 1, followed by a 6 mg/kg on Cycle 2, Day 1 once every three weeks)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 1, Cohort 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SNK01 (high dose) administered once every three weeks in combination with trastuzumab (loading dose of 8 mg/kg on Cycle 1, Day 1, followed by a 6 mg/kg on Cycle 2, Day 1 once every three weeks)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 1, Cohort 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SNK01 (low dose) administered once every week in combination with cetuximab (loading dose of 400 mg/m2 on Cycle 1, Day 1, followed by a 250 mg/m2 on Cycle 2, Day 1 once every week)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 1, Cohort 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SNK01 (high dose) administered once every week in combination with cetuximab (loading dose of 400 mg/m2 on Cycle 1, Day 1, followed by a 250 mg/m2 on Cycle 2, Day 1 once every week)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 2, Expansion Cohort 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SNK01 (TBD RP2D) administered once every three weeks in combination with trastuzumab (loading dose of 8 mg/kg on Cycle 1, Day 1, followed by a 6 mg/kg on Cycle 2, Day 1 once every three weeks)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 2, Expansion Cohort 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SNK01 (TBD RP2D) administered once every week in combination with cetuximab (loading dose of 400 mg/m2 on Cycle 1, Day 1, followed by a 250 mg/m2 on Cycle 2, Day 1 once every week)</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>SNK01</intervention_name>
    <description>Patient-specific ex vivo expanded autologous natural killer cells</description>
    <arm_group_label>Phase 1, Cohort 1</arm_group_label>
    <arm_group_label>Phase 1, Cohort 2</arm_group_label>
    <arm_group_label>Phase 1, Cohort 3</arm_group_label>
    <arm_group_label>Phase 1, Cohort 4</arm_group_label>
    <arm_group_label>Phase 2, Expansion Cohort 1</arm_group_label>
    <arm_group_label>Phase 2, Expansion Cohort 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trastuzumab</intervention_name>
    <description>HER2 receptor antagonistic, humanized immunoglobulin G subclass 1 (IgG1) monoclonal antibody</description>
    <arm_group_label>Phase 1, Cohort 1</arm_group_label>
    <arm_group_label>Phase 1, Cohort 2</arm_group_label>
    <arm_group_label>Phase 2, Expansion Cohort 1</arm_group_label>
    <other_name>Herceptin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cetuximab</intervention_name>
    <description>EGFR antagonist, chimeric immunoglobulin G subclass 1 (IgG1) monoclonal antibody</description>
    <arm_group_label>Phase 1, Cohort 3</arm_group_label>
    <arm_group_label>Phase 1, Cohort 4</arm_group_label>
    <arm_group_label>Phase 2, Expansion Cohort 2</arm_group_label>
    <other_name>Erbitux</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Capable of giving signed informed consent which includes compliance with the&#xD;
             requirements and restrictions listed in the informed consent form and protocol.&#xD;
&#xD;
          -  Males and females ages 18 to 75 years, inclusive.&#xD;
&#xD;
          -  Diagnosed with any documented histologically confirmed HER2 or EGFR-positive&#xD;
             malignancy whose disease is confirmed to be metastatic and/or unresectable for which&#xD;
             all treatment options considered to be standard of care therapy appropriate for the&#xD;
             specific tumor type have been received and are no longer effective (i.e., subjects are&#xD;
             refractory to standard of care therapies).&#xD;
&#xD;
          -  One or more tumors measurable per RECIST v1.1&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1&#xD;
&#xD;
          -  At least 4 weeks since any prior systemic therapy (excluding corticosteroid therapy)&#xD;
             to treat the underlying malignancy (standard or investigational).&#xD;
&#xD;
          -  At least 2 weeks since prior palliative radiotherapy.&#xD;
&#xD;
          -  Left ventricular ejection fraction (LVEF) ≥50% measured by multiple-gated acquisition&#xD;
             scan (MUGA) or echocardiogram (ECHO).&#xD;
&#xD;
          -  Adequate organ function as determined by:&#xD;
&#xD;
             a. Hematological (without growth factor or transfusion support within 14 days prior to&#xD;
             screening): i. Absolute neutrophil count ≥ 1.5 × 109/L (1,500/mm3) ii. Platelet count&#xD;
             ≥ 75 × 109/L (75,000/mm3) iii. Hemoglobin ≥ 9.0 g/dL iv. Prothrombin&#xD;
             time-international normalized ratio and partial thromboplastin time ≤ 1.5 × upper&#xD;
             limit normal (ULN)&#xD;
&#xD;
             b. Renal: i. Calculated creatinine clearance (CrCl) or 24 hour urine CrCl &gt; 50&#xD;
             mL/minute (Note: Cockcroft-Gault formula will be used to calculate CrCl)&#xD;
&#xD;
             c. Hepatic: i. Total bilirubin ≤ 1.5 × ULN; for subjects with documented/suspected&#xD;
             Gilbert's disease, bilirubin ≤ 3 × ULN ii. Aspartate aminotransferase (AST) and&#xD;
             alanine aminotransferase (ALT) ≤ 2.5 × ULN (AST/ALT can be up to 5 × ULN in the&#xD;
             presence of liver metastasis, but cannot be associated with concurrent elevated&#xD;
             bilirubin)&#xD;
&#xD;
             d. Serum electrolytes: i. Potassium, sodium, magnesium, and calcium (corrected for&#xD;
             serum albumin) ≤ Grade 1 or within the institutional ranges of normal. If clinically&#xD;
             appropriate, electrolytes may be corrected and values re-assessed prior to enrollment.&#xD;
&#xD;
          -  Women of childbearing potential who are not abstinent and intend to be sexually active&#xD;
             with a nonsterilized male partner must be willing to use an adequate method of&#xD;
             contraception from 28 days prior to the first study drug(s) administration and 120&#xD;
             days following last day of the last administration of last study drug(s) discontinued;&#xD;
             acceptable methods include hormonal contraception (oral contraceptives - as long as on&#xD;
             stable dose, patch, implant, and injection), intrauterine devices, or double barrier&#xD;
             methods (e.g., vaginal diaphragm/vaginal sponge plus condom, or condom plus&#xD;
             spermicidal jelly), sexual abstinence or a vasectomized partner. Women may be&#xD;
             surgically sterile for at least 1 year after last menstrual period.&#xD;
&#xD;
          -  Male subjects: Non-sterilized male subjects who are not abstinent and intend to be&#xD;
             sexually active with a female partner of childbearing potential must use a male condom&#xD;
             plus spermicide from 28 days prior to the first study drug(s) administration&#xD;
             throughout the total duration of the treatment period and 120 days after the last dose&#xD;
             of last study drug(s) discontinued. Periodic abstinence, the rhythm method, and the&#xD;
             withdrawal method are not acceptable methods of contraception. Male subjects should&#xD;
             refrain from sperm donation throughout this period.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant and/or lactating females. Women of childbearing potential must have negative&#xD;
             serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within&#xD;
             14 days prior to receiving the first administration of the study drug(s) and a&#xD;
             negative urine pregnancy test on Day 1 before first administration of the study&#xD;
             drug(s). If the urine test is positive or cannot be confirmed as negative, a serum&#xD;
             pregnancy test is required.&#xD;
&#xD;
          -  Life expectancy of less than three months.&#xD;
&#xD;
          -  Currently being treated with immunotherapy or received immunotherapy during the&#xD;
             treatment regimen immediately prior to participation in this study.&#xD;
&#xD;
          -  Untreated for HER2- or EGFR-positive metastatic and/or unresectable malignancy OR have&#xD;
             refused an available standard of care therapy appropriate for the specific tumor type&#xD;
             for any reason other than for a known sensitivity, toxicity, or contraindication.&#xD;
&#xD;
          -  For EGFR-positive patients, first line cetuximab treatment stopped due to allergic&#xD;
             response.&#xD;
&#xD;
          -  For EGFR-positive patients, superior vena cava syndrome contra-indicating hydration.&#xD;
&#xD;
          -  Untreated or symptomatic central nervous system (CNS) metastases. Note: Subjects with&#xD;
             asymptomatic treated CNS metastases are eligible provided they have been clinically&#xD;
             stable and not requiring steroid treatment for at least 4 weeks.&#xD;
&#xD;
          -  No resolution of specific toxicities related to any prior anti-cancer therapy to Grade&#xD;
             ≤1 according to the NCI-CTCAE v.5.0 (except lymphopenia and alopecia).&#xD;
&#xD;
          -  Active peripheral or motor neuropathy of any CTCAE grade and due to any cause.&#xD;
&#xD;
          -  Known hypersensitivity or allergy or contraindication to at least one of the study&#xD;
             drugs.&#xD;
&#xD;
          -  In case of previous chemotherapy, wash out period of less than 5 half-lives of&#xD;
             treatment before study entry.&#xD;
&#xD;
          -  Clinically significant cardiovascular disease including:&#xD;
&#xD;
               1. Myocardial infarction within 3 months,&#xD;
&#xD;
               2. Congestive heart failure of the New York Heart Association (NYHA) class 3 or 4,&#xD;
                  or patients with history of congestive heart failure NYHA class 3 or 4 in the&#xD;
                  past, unless a screening LVEF assessment ≥ 45%,&#xD;
&#xD;
               3. Prolonged QT interval defined as screening corrected QT interval (QTc) &gt; 470 ms&#xD;
                  (Fridericia correction formula),&#xD;
&#xD;
               4. History of clinically significant ventricular arrhythmia (e.g., ventricular&#xD;
                  tachycardia, ventricular fibrillation),&#xD;
&#xD;
               5. History of Mobitz II 2nd degree or 3rd degree heart block without a permanent&#xD;
                  pacemaker in place,&#xD;
&#xD;
               6. Hypotension (systolic blood pressure [BP] &lt; 86 mmHg) or bradycardia with a heart&#xD;
                  rate &lt; 50 bpm,&#xD;
&#xD;
               7. Uncontrolled hypertension as indicated by a resting systolic BP &gt; 170 mmHg or&#xD;
                  diastolic BP &gt; 105 mmHg despite an optimal treatment,&#xD;
&#xD;
          -  Major surgery within 4 weeks prior first study drug administration or already planned&#xD;
             during the study.&#xD;
&#xD;
          -  Currently participating in or has participated in a study of an investigational agent&#xD;
             or has used an investigational device within 4 weeks prior to the first dose of study&#xD;
             drug(s). (Note: Subjects participating in an observational study are an exception to&#xD;
             this criterion and may qualify for the study with Sponsor approval)&#xD;
&#xD;
          -  Any pulmonary, thyroid, renal, hepatic severe/uncontrolled concurrent medical disease&#xD;
             that in the opinion of the Investigator could cause unacceptable safety risks or&#xD;
             compromise compliance with the protocol.&#xD;
&#xD;
          -  Active uncontrolled viral, fungal or bacterial infection requiring systematic therapy&#xD;
             within 14 days of Day 1.&#xD;
&#xD;
          -  High fever or any active or unresolved infection.&#xD;
&#xD;
          -  Known history of testing positive for human immunodeficiency virus (HIV), and/or&#xD;
             positive test for Hepatitis B virus surface antigen (HBsAg) and/or positive Hep C&#xD;
             antibody result with detectable hepatitis C virus (HCV) ribonucleic acid (RNA)&#xD;
             indicating acute or chronic infection.&#xD;
&#xD;
          -  Autoimmune disease requiring therapy; immunodeficiency, or any disease process&#xD;
             requiring immunosuppressive therapy.&#xD;
&#xD;
          -  A serious nonmalignant disease (e.g., psychiatric, substance abuse, uncontrolled&#xD;
             intercurrent illness, etc.) that could compromise protocol objectives in the opinion&#xD;
             of the Investigator and/or the Sponsor.&#xD;
&#xD;
          -  Any other condition that, in the opinion of the Investigator, would prohibit the&#xD;
             subject from participating in the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Paul Y. Song, MD</last_name>
    <role>Study Director</role>
    <affiliation>NKGen Biotech, Inc.</affiliation>
  </overall_official>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>July 1, 2020</study_first_submitted>
  <study_first_submitted_qc>July 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 9, 2020</study_first_posted>
  <last_update_submitted>May 10, 2021</last_update_submitted>
  <last_update_submitted_qc>May 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 12, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Natural killer cell</keyword>
  <keyword>NK cell</keyword>
  <keyword>Expanded natural killer cell</keyword>
  <keyword>Immunotherapy</keyword>
  <keyword>Cancer</keyword>
  <keyword>Metastatic cancer</keyword>
  <keyword>Advanced cancer</keyword>
  <keyword>Recurrent cancer</keyword>
  <keyword>HER2 Positive</keyword>
  <keyword>HER2+</keyword>
  <keyword>HER2</keyword>
  <keyword>EGFR Positive</keyword>
  <keyword>EGFR+</keyword>
  <keyword>EGFR</keyword>
  <keyword>Solid tumor</keyword>
  <keyword>Breast Cancer</keyword>
  <keyword>Gastric Cancer</keyword>
  <keyword>Esophageal Cancer</keyword>
  <keyword>Ovarian Cancer</keyword>
  <keyword>Endometrium Cancer</keyword>
  <keyword>Bladder Cancer</keyword>
  <keyword>Pancreatic Cancer</keyword>
  <keyword>Colorectal Cancer</keyword>
  <keyword>Non Small Cell Lung Cancer</keyword>
  <keyword>Head and Neck Squamous Cell Carcinoma</keyword>
  <keyword>Triple Negative Breast Cancer</keyword>
  <keyword>Cervical Cancer</keyword>
  <keyword>Sarcoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
    <mesh_term>Colorectal Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Pancreatic Neoplasms</mesh_term>
    <mesh_term>Ovarian Neoplasms</mesh_term>
    <mesh_term>Sarcoma</mesh_term>
    <mesh_term>Stomach Neoplasms</mesh_term>
    <mesh_term>Uterine Cervical Neoplasms</mesh_term>
    <mesh_term>Urinary Bladder Neoplasms</mesh_term>
    <mesh_term>Esophageal Neoplasms</mesh_term>
    <mesh_term>Triple Negative Breast Neoplasms</mesh_term>
    <mesh_term>Neoplasm Metastasis</mesh_term>
    <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
    <mesh_term>Endometrial Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Trastuzumab</mesh_term>
    <mesh_term>Cetuximab</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/NCT04464967
org study id: SNK01-102
nct id: NCT04464967
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
The purpose of the Phase 1/2a study is to evaluate the safety and tolerability of SNK01 in
      combination with trastuzumab or cetuximab in order to determine the maximum tolerated dose
      (MTD)/recommended Phase 2 dose (RP2D), and the preliminary efficacy for each combination
      regimen.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Phase 1 - To determine recommended Phase 2 dose (RP2D) of SNK01 in combination with trastuzumab in subjects with advanced HER2 cancers.
time frame: Up to 6 months
description: Evaluated by the number of DLTs graded using NCI CTCAE v5.0.
measure: Phase 1 - To determine recommended Phase 2 dose (RP2D) of SNK01 in combination with cetuximab in subjects with advanced EGFR cancers.
time frame: Up to 6 months
description: Evaluated by the number of DLTs graded using NCI CTCAE v5.0.
measure: Phase 2a - To assess objective response rate (ORR) of SNK01 in combination with trastuzumab in subjects with advanced HER2 cancers.
time frame: Up to 12 months
description: Defined by percentage of subjects with a best response of complete response (CR), partial response (PR) or stable disease (SD) by investigator assessment per RECIST 1.1.
measure: Phase 2a - To assess objective response rate (ORR) of SNK01 in combination with cetuximab in subjects with advanced EGFR cancers.
time frame: Up to 12 months
description: Defined by percentage of subjects with a best response of complete response (CR), partial response (PR) or stable disease (SD) by investigator assessment per RECIST 1.1.
measure: Phase 2a - To assess the progression-free survival (PFS) of SNK01 in combination with trastuzumab in subjects with advanced HER2 cancers.
time frame: Up to 12 months
description: Defined by the time of the date of first dose of study drug until confirmed disease progression based on investigator assessment per RECIST 1.1 or death from any cause, whichever comes first.
measure: Phase 2a - To assess the progression-free survival (PFS) of SNK01 in combination with cetuximab in subjects with advanced EGFR cancers.
time frame: Up to 12 months
description: Defined by the time of the date of first dose of study drug until confirmed disease progression based on investigator assessment per RECIST 1.1 or death from any cause, whichever comes first.
measure: Phase 2a - To assess the overall survival (OS) of SNK01 in combination with trastuzumab in subjects with advanced HER2 cancers.
time frame: Up to 24 months
description: Defined as time from first dose of study drug to death due to any cause.
measure: Phase 2a - To assess the overall survival (OS) of SNK01 in combination with cetuximab in subjects with advanced EGFR cancers.
time frame: Up to 24 months
description: Defined as time from first dose of study drug to death due to any cause.
measure: Phase 2a - To assess the duration of response (DOR) of SNK01 in combination with trastuzumab in subjects with advanced HER2 cancers.
time frame: Up to 12 months
description: Defined as duration of time from initial response (complete response [CR] or partial response [PR]) to first documentation of disease progression or death from any cause, whichever occurs first.
measure: Phase 2a - To assess the duration of response (DOR) of SNK01 in combination with cetuximab in subjects with advanced EGFR cancers.
time frame: Up to 12 months
description: Defined as duration of time from initial response (complete response [CR] or partial response [PR]) to first documentation of disease progression or death from any cause, whichever occurs first.
measure: Phase 2a - To assess the clinical benefit rate (CBR) of SNK01 in combination with trastuzumab in subjects with advanced HER2 cancers.
time frame: Up to 12 months
description: Defined as proportion of subjects who achieve an overall tumor response (complete response [CR] or partial response [PR] or stable disease [SD]).
measure: Phase 2a - To assess the clinical benefit rate (CBR) of SNK01 in combination with cetuximab in subjects with advanced EGFR cancers.
time frame: Up to 12 months
description: Defined as proportion of subjects who achieve an overall tumor response (complete response [CR] or partial response [PR] or stable disease [SD]).
measure: Phase 2a - Impact of SNK01 in combination with trastuzumab on quality of life in subjects with advanced HER2 cancers evaluated using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30).
time frame: Up to 12 months
description: The EORTC QLQ-C30 questionnaire consists of 30 questions, 24 of which are grouped into nine multi-item scales (five functioning scales [physical, role, cognitive, emotional and social], three symptom scales [fatigue, pain and nausea/vomiting] and one global health status scale). The remaining six questions are single-item scales (dyspnea, appetite loss, sleep disturbance, constipation, diarrhea and the financial impact) and are intended to assess symptoms.
All of the scales and single-item measures are scored on a scale from 0 to 100. A better state of the patient is denoted by a higher score for the functioning scales and global health status, while a worsening state of the patient is denoted by higher scores on the symptom and single-item scales.
measure: Phase 2a - Impact of SNK01 in combination with cetuximab on quality of life in subjects with advanced EGFR cancers evaluated using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30).
time frame: Up to 12 months
description: The EORTC QLQ-C30 questionnaire consists of 30 questions, 24 of which are grouped into nine multi-item scales (five functioning scales [physical, role, cognitive, emotional and social], three symptom scales [fatigue, pain and nausea/vomiting] and one global health status scale). The remaining six questions are single-item scales (dyspnea, appetite loss, sleep disturbance, constipation, diarrhea and the financial impact) and are intended to assess symptoms.
All of the scales and single-item measures are scored on a scale from 0 to 100. A better state of the patient is denoted by a higher score for the functioning scales and global health status, while a worsening state of the patient is denoted by higher scores on the symptom and single-item scales.
measure: Phase 2a-Impact of SNK01 in combination with trastuzumab on quality of life in subjects with advanced HER2 cancers evaluated using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer 13 (QLQ-LC13).
time frame: Up to 12 months
description: The EORTC QLQ-LC13 is a supplementary lung-cancer specific questionnaire and is used in conjunction with the EORTC QLQ-C30 questionnaire. It is comprised of 13 questions, 3 of which are grouped into a multi-item scale to assess dyspnea and 10 of which are single-item scales assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis.
All of the scales and single-item measures are scored on a scale from 0 to 100. A better state of the patient is denoted by a higher score for the functioning scales and global health status, while a worsening state of the patient is denoted by higher scores on the symptom and single-item scales.
measure: Phase 2a - Impact of SNK01 in combination with cetuximab on quality of life in subjects with advanced EGFR cancers evaluated using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer 13 (QLQ-LC13).
time frame: Up to 12 months
description: The EORTC QLQ-LC13 is a supplementary lung-cancer specific questionnaire and is used in conjunction with the EORTC QLQ-C30 questionnaire. It is comprised of 13 questions, 3 of which are grouped into a multi-item scale to assess dyspnea and 10 of which are single-item scales assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis.
All of the scales and single-item measures are scored on a scale from 0 to 100. A better state of the patient is denoted by a higher score for the functioning scales and global health status, while a worsening state of the patient is denoted by higher scores on the symptom and single-item scales.
arm group label: Phase 1, Cohort 1
arm group type: Experimental
description: SNK01 (low dose) administered once every three weeks in combination with trastuzumab (loading dose of 8 mg/kg on Cycle 1, Day 1, followed by a 6 mg/kg on Cycle 2, Day 1 once every three weeks)
arm group label: Phase 1, Cohort 2
arm group type: Experimental
description: SNK01 (high dose) administered once every three weeks in combination with trastuzumab (loading dose of 8 mg/kg on Cycle 1, Day 1, followed by a 6 mg/kg on Cycle 2, Day 1 once every three weeks)
arm group label: Phase 1, Cohort 3
arm group type: Experimental
description: SNK01 (low dose) administered once every week in combination with cetuximab (loading dose of 400 mg/m2 on Cycle 1, Day 1, followed by a 250 mg/m2 on Cycle 2, Day 1 once every week)
arm group label: Phase 1, Cohort 4
arm group type: Experimental
description: SNK01 (high dose) administered once every week in combination with cetuximab (loading dose of 400 mg/m2 on Cycle 1, Day 1, followed by a 250 mg/m2 on Cycle 2, Day 1 once every week)
arm group label: Phase 2, Expansion Cohort 1
arm group type: Experimental
description: SNK01 (TBD RP2D) administered once every three weeks in combination with trastuzumab (loading dose of 8 mg/kg on Cycle 1, Day 1, followed by a 6 mg/kg on Cycle 2, Day 1 once every three weeks)
arm group label: Phase 2, Expansion Cohort 2
arm group type: Experimental
description: SNK01 (TBD RP2D) administered once every week in combination with cetuximab (loading dose of 400 mg/m2 on Cycle 1, Day 1, followed by a 250 mg/m2 on Cycle 2, Day 1 once every week)
intervention type: Biological
intervention name: SNK01
description: Patient-specific ex vivo expanded autologous natural killer cells
arm group label: Phase 1, Cohort 1
arm group label: Phase 1, Cohort 2
arm group label: Phase 1, Cohort 3
arm group label: Phase 1, Cohort 4
arm group label: Phase 2, Expansion Cohort 1
arm group label: Phase 2, Expansion Cohort 2
intervention type: Drug
intervention name: Trastuzumab
description: HER2 receptor antagonistic, humanized immunoglobulin G subclass 1 (IgG1) monoclonal antibody
arm group label: Phase 1, Cohort 1
arm group label: Phase 1, Cohort 2
arm group label: Phase 2, Expansion Cohort 1
other name: Herceptin
intervention type: Drug
intervention name: Cetuximab
description: EGFR antagonist, chimeric immunoglobulin G subclass 1 (IgG1) monoclonal antibody
arm group label: Phase 1, Cohort 3
arm group label: Phase 1, Cohort 4
arm group label: Phase 2, Expansion Cohort 2
other name: Erbitux
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Paul Y. Song, MD
role: Study Director
affiliation: NKGen Biotech, Inc.
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Colorectal Neoplasms
mesh term: Carcinoma, Squamous Cell
mesh term: Pancreatic Neoplasms
mesh term: Ovarian Neoplasms
mesh term: Sarcoma
mesh term: Stomach Neoplasms
mesh term: Uterine Cervical Neoplasms
mesh term: Urinary Bladder Neoplasms
mesh term: Esophageal Neoplasms
mesh term: Triple Negative Breast Neoplasms
mesh term: Neoplasm Metastasis
mesh term: Squamous Cell Carcinoma of Head and Neck
mesh term: Endometrial Neoplasms
mesh term: Trastuzumab
mesh term: Cetuximab