<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/NCT02981303</url>
  </required_header>
  <id_info>
    <org_study_id>BT-CL-PGG-MEL/BCA-1621/MK3475</org_study_id>
    <nct_id>NCT02981303</nct_id>
  </id_info>
  <brief_title>Study of Imprime PGG and Pembrolizumab in Advanced Melanoma and Triple Negative Breast Cancer</brief_title>
  <official_title>A Multicenter, Open-label, Phase 2 Study of Imprime PGG and Pembrolizumab in Subjects With Advanced Melanoma Failing Front-line Treatment With Checkpoint Inhibitors (CPI) or TNBC Failing Front-line Chemotherapy for Metastatic Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>HiberCell, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>HiberCell, 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>
      Objective: To determine the Overall Response Rate (ORR) to Imprime PGG + pembrolizumab in&#xD;
      subjects with advanced melanoma or metastatic TNBC&#xD;
&#xD;
      Safety: To characterize the safety of Imprime PGG + pembrolizumab given in combination&#xD;
&#xD;
      Hypothesis: Restore (for melanoma) or enhance (for TNBC) sensitivity to checkpoint inhibitors&#xD;
      (CPI) by appropriate and effective stimulation of the subject's innate and adaptive immune&#xD;
      systems in those subjects who have failed 1st line therapy&#xD;
&#xD;
      The study will incorporate Simon's optimal 2-stage design with sample size fixed at 12&#xD;
      subjects each in Stage 1 for advanced melanoma and for Triple Negative Breast Cancer (TNBC)&#xD;
      subjects. The safety criterion of ≤ 4 (or ≤ 33%) subjects with Grade 3/4 adverse events in&#xD;
      Cycle 1 within either tumor type must be met in order to proceed to Stage 2. The starting&#xD;
      dose is 4 mg/kg for Imprime PGG. In the event there are a total of &gt; 4 (or &gt; 33%) of subjects&#xD;
      with Grade 3/4 adverse events in Cycle 1, the dose of Imprime PGG will be reduced to 2 mg/kg,&#xD;
      and Stage 1 will be repeated at a dose of 2 mg/kg with an additional cohort of n=12 subjects.&#xD;
      For the dose that meets the safety criterion in Stage 1, at least 1 response in melanoma&#xD;
      subjects and 2 responses in TNBC subjects amongst the 12 subjects within each tumor type must&#xD;
      be observed in order to proceed to Stage 2.&#xD;
&#xD;
      Stage 2 will enroll an additional 17 subjects with melanoma, and 30 subjects with TNBC. For&#xD;
      the dose that meets the Stage 1 safety criterion, success will be declared if at least 4&#xD;
      amongst the total of up to 29 subjects with melanoma, and 13 amongst the total of up to 42&#xD;
      subjects with TNBC achieve an objective response.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 22, 2017</start_date>
  <completion_date type="Actual">December 31, 2020</completion_date>
  <primary_completion_date type="Actual">December 31, 2020</primary_completion_date>
  <phase>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>Overall Response Rate (ORR) to Imprime PGG + pembrolizumab using RECIST v1.1 criteria</measure>
    <time_frame>Within 18 months of last patient enrolled</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to response (TTR) using RECIST v1.1 criteria</measure>
    <time_frame>Within 24 months of last patient enrolled</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complete response rate (CRR) using RECIST v1.1 criteria</measure>
    <time_frame>Within 24 months of last patient enrolled</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of overall response (DoR) using RECIST v1.1 criteria</measure>
    <time_frame>Within 24 months of last patient enrolled</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival (PFS) and PFS rate at 6 months and 1 year using RECIST v1.1 criteria</measure>
    <time_frame>Within 24 months of last patient enrolled</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS) and OS rate at 1 year using RECIST v1.1 criteria</measure>
    <time_frame>Within 24 months of last patient enrolled</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic (PK) data of Imprime PGG in combination with Pembrolizumab</measure>
    <time_frame>Within 24 months of last patient enrolled</time_frame>
    <description>Correlate serum Imprime PGG concentration/time relationship</description>
  </secondary_outcome>
  <other_outcome>
    <measure>ORR based on irRECIST</measure>
    <time_frame>Within 24 months of last patient enrolled</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>PFS based on irRECIST</measure>
    <time_frame>Within 24 months of last patient enrolled</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Correlate levels of baseline serum anti-β-glucan antibody (ABA) with objective response and treatment outcomes</measure>
    <time_frame>Within 24 months of last patient enrolled</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Correlate changes in immune cell activation markers, such as CD86 expression in tumor biopsy samples* and in peripheral blood immune cells with objective response and treatment outcome</measure>
    <time_frame>Within 24 months of last patient enrolled</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>In tumor biopsies, correlate changes in the tumor immune microenvironment including TILs (Tumor-infiltrating Lymphocytes) and tumor-infiltrating myeloid cells with objective response and treatment outcome</measure>
    <time_frame>Within 24 months of last patient enrolled</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Correlate PD-L1 expression in tumor biopsy samples (in tumor cells and myeloid cells) with objective response and treatment outcome</measure>
    <time_frame>Within 24 months of last patient enrolled</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">64</enrollment>
  <condition>Advanced Melanoma</condition>
  <condition>Triple-Negative Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Melanoma</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Imprime PGG + Pembrolizumab</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Triple Negative Breast Cancer</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Imprime PGG + Pembrolizumab</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Imprime PGG</intervention_name>
    <description>Imprime PGG is a soluble, β-1,3/1,6 glucan isolated from the cell wall of a proprietary Saccharomyces cerevisiae yeast strain. Imprime PGG acts as a Pathogen-Associated Molecular Pattern (PAMP). Imprime will be administered at a dose of 4 mg/kg IV over a 2-hour infusion time on Days 1, 8 and 15 of each 3-week treatment cycle.</description>
    <arm_group_label>Melanoma</arm_group_label>
    <arm_group_label>Triple Negative Breast Cancer</arm_group_label>
    <other_name>Imprime</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>Pembrolizumab is a humanized monoclonal antibody against the programmed death receptor-1 protein. Pembrolizumab will be given at a fixed dose of 200 mg IV over 30 minutes on Day 1 of each 3-week treatment cycle after the Imprime infusion.</description>
    <arm_group_label>Melanoma</arm_group_label>
    <arm_group_label>Triple Negative Breast Cancer</arm_group_label>
    <other_name>Keytruda</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Have signed an informed document prior to any study-specific procedures or treatment&#xD;
&#xD;
          2. Be ≥ 18 years of age at time of consent&#xD;
&#xD;
          3. For Melanoma Subjects: Have histologically or cytologically confirmed diagnosis of&#xD;
             unresectable Stage III or metastatic (Stage IV) melanoma not amenable to local&#xD;
             therapy, and irrespective of PD-L1 status&#xD;
&#xD;
          4. For TNBC Subjects: Have histologically or cytologically confirmed diagnosis of&#xD;
             metastatic (Stage IV) TNBC, and irrespective of PD-L1 status. TNBC is defined as&#xD;
             negative immunohistochemistry (IHC) assays for Estrogen Receptor (ER), and&#xD;
             Progesterone Receptor (PR), and HER2 negative (IHC 0 or 1+, or 2+ by IHC confirmed&#xD;
             negative by FISH)&#xD;
&#xD;
          5. Have documented objective radiographic or clinical disease progression after&#xD;
             PD-1/PD-L1 +/- anti-CTLA-4 inhibitor therapy (melanoma) or after at least 1 line of&#xD;
             chemotherapy for metastatic disease (TNBC)&#xD;
&#xD;
          6. Have resolution of all previous treatment-related toxicities to Grade 1 severity or&#xD;
             lower, except for stable sensory neuropathy (less than or equal to Grade 2) or&#xD;
             alopecia. If subject received major surgery or radiation therapy of &gt; 30 Gy, must have&#xD;
             recovered from the toxicity and/or complications from the intervention.&#xD;
&#xD;
          7. Have at least one radiologically measurable lesion as per RECIST v1.1 defined as a&#xD;
             lesion that is at least 10 mm in longest diameter or lymph node that is at least 15 mm&#xD;
             in short axis imaged by CT scan or MRI and obtained by imaging within 28 days prior to&#xD;
             start of study treatment. Tumor lesions situated in a previously irradiated area are&#xD;
             considered measurable if progression has been demonstrated in such lesions.&#xD;
&#xD;
          8. Have peripheral blood levels of IgG anti-β-glucan antibody (ABA) of ≥ 20 mcg/mL as&#xD;
             determined by an ELISA test within 28 days prior to start of study treatment&#xD;
&#xD;
          9. Be willing to consider providing fresh tissue for biomarker analysis, and, based on&#xD;
             the adequacy of the tissue sample quality, for assessment of biomarker status. Repeat&#xD;
             samples may be required if adequate tissue is not provided. Newly obtained biopsy&#xD;
             specimens are preferred to archived samples and formalin-fixed, paraffin-embedded&#xD;
             block specimens are preferred to slides.&#xD;
&#xD;
             Note: Information on 1 tumor biopsy sample is mandatory and is as follows: (1) To&#xD;
             determine eligibility, historical (diagnostic) tumor biopsy official pathology report&#xD;
             +/- an archival sample. Additional biopsy samples, preferably obtained from the same&#xD;
             localized region, are highly desirable when feasible at the following time points: (2)&#xD;
             Sample before the first dose of study treatment, (3) Sample after completion of Cycle&#xD;
             2 but before the start of Cycle 3 dosing, and (4) Sample either at the time of&#xD;
             response or at the End of Study Visit (if no response).&#xD;
&#xD;
         10. Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (see&#xD;
             Appendix 14.3)&#xD;
&#xD;
         11. Have life expectancy of 3 months or greater as determined by the treating physician&#xD;
&#xD;
         12. Have adequate organ function (all screening labs should be performed within 15 days&#xD;
             prior to treatment initiation):&#xD;
&#xD;
               1. Total bilirubin ≤ 1.5 × upper limit of normal (ULN) OR direct bilirubin ≤ ULN for&#xD;
                  subjects with total bilirubin levels &gt; 1.5 x ULN&#xD;
&#xD;
               2. Aspartate aminotransferase (AST) ≤ 2.5 × ULN or ≤ 5 × ULN for subjects with known&#xD;
                  hepatic metastases&#xD;
&#xD;
               3. Alanine aminotransferase (ALT) ≤ 2.5 × ULN or ≤ 5 × ULN for subjects with known&#xD;
                  hepatic metastases&#xD;
&#xD;
         13. Have adequate renal function as defined by the following criteria:&#xD;
&#xD;
             Creatinine ≤ 1.5 x ULN and CrCl ≥ 30 ml/min per Cockcroft Gault formula:&#xD;
&#xD;
         14. Have adequate hematologic function, defined as meeting all of the following criteria:&#xD;
&#xD;
               1. Hemoglobin ≥ 9 g/dL (uncorrected by RBC transfusion)&#xD;
&#xD;
               2. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L&#xD;
&#xD;
               3. Platelet count ≥ 100 × 109/L&#xD;
&#xD;
         15. Have adequate coagulation functioning within 15 days prior to start of study&#xD;
             treatment, defined by either of the following criteria:&#xD;
&#xD;
               1. INR &lt; 1.5 × ULN&#xD;
&#xD;
               2. OR for subjects receiving warfarin or low molecular weight heparin (LMWH), the&#xD;
                  subjects must, in the Investigator's opinion, be clinically stable with no&#xD;
                  evidence of active bleeding while receiving anticoagulant therapy. The INR for&#xD;
                  these subjects may exceed 1.5 × ULN if that is the goal of anticoagulant therapy.&#xD;
&#xD;
               3. Activated Partial Thromboplastin Time (aPTT) &lt; 1.5 × ULN unless subject is&#xD;
                  receiving anticoagulant therapy as long as PT or PTT is within therapeutic range&#xD;
                  of intended use of anticoagulants&#xD;
&#xD;
         16. Female subjects of childbearing potential as defined in Section 5.7.2 must have a&#xD;
             negative urine or serum pregnancy within 72 hours prior to receiving the first dose of&#xD;
             study medication. If the urine test is positive or cannot be confirmed as negative, a&#xD;
             serum pregnancy test will be required.&#xD;
&#xD;
         17. If of childbearing potential as defined in Section 5.7.2, must be willing to use an&#xD;
             adequate method of contraception (see Section 5.7.2) from the first dose of study&#xD;
             medication through 120 days after the last dose of study medication&#xD;
&#xD;
         18. Be willing and have the ability to comply with scheduled visits (including&#xD;
             geographical proximity), treatment plans, laboratory tests, and other study procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Has disease that is suitable for local therapy administered with curative intent&#xD;
&#xD;
          2. Is currently participating and receiving study therapy or has participated in a study&#xD;
             of an investigational agent and received study therapy or used an investigational&#xD;
             device within 4 weeks of the first dose of treatment&#xD;
&#xD;
          3. Has a diagnosis of immunodeficiency or receiving systemic steroid therapy or any other&#xD;
             form of immunosuppressive therapy within 7 days prior to the first dose of study&#xD;
             treatment. The use of physiologic doses of corticosteroids may be approved after&#xD;
             consultation with the Sponsor.&#xD;
&#xD;
          4. Has known history of active tuberculosis&#xD;
&#xD;
          5. Has known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)&#xD;
&#xD;
          6. Has known active Hepatitis B (eg, HBsAg reactive) or Hepatitis C (eg, HCV RNA&#xD;
             [qualitative] is detected&#xD;
&#xD;
          7. Has a history of clinically severe autoimmune disease, or history of organ transplant&#xD;
&#xD;
          8. Has a history of ocular melanoma&#xD;
&#xD;
          9. Has known hypersensitivity to baker's yeast&#xD;
&#xD;
         10. Had previous exposure to Betafectin® or Imprime PGG&#xD;
&#xD;
         11. Has hypersensitivity to pembrolizumab or any of its excipients&#xD;
&#xD;
         12. Had a prior anti-cancer monoclonal antibody (except immune CPI in the case of melanoma&#xD;
             subjects) within 30 days prior to start of study treatment, or failure to recover to&#xD;
             CTCAE Grade 1 or better from the adverse events of prior therapies&#xD;
&#xD;
         13. Had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2&#xD;
             weeks prior to Study Day 1 or who has not recovered from adverse events due to a&#xD;
             previously administered agent or major surgery&#xD;
&#xD;
         14. Has received transfusion of blood products (including platelets or red blood cells) or&#xD;
             administration of colony stimulating factors (including G-CSF, GM-CSF, or recombinant&#xD;
             erythropoietin) within 4 weeks prior to Study Day 1&#xD;
&#xD;
         15. Has known additional malignancy that is progressing or requires active treatment.&#xD;
             Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the&#xD;
             skin that has undergone potentially curative therapy or in situ cervical cancer.&#xD;
&#xD;
         16. Has known active central nervous system metastases and/or carcinomatous meningitis.&#xD;
             Subjects with previously treated brain metastases may participate provided they are&#xD;
             stable (without evidence of progression by imaging for at least 4 weeks prior to the&#xD;
             first dose of trial treatment and any neurologic symptoms have returned to baseline),&#xD;
             have no evidence of new or enlarging brain metastases, and are not using steroids for&#xD;
             at least 7 days prior to trial treatment. This exception does not include&#xD;
             carcinomatous meningitis, which is excluded regardless of clinical stability.&#xD;
&#xD;
         17. Has active autoimmune disease requiring systemic treatment in the past 2 years (ie,&#xD;
             with use of disease modifying agents, corticosteroids or immunosuppressive drugs).&#xD;
             Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteriod replacement&#xD;
             therapy for adrenal or pituitary insufficiency) is not considered a form of systemic&#xD;
             treatment.&#xD;
&#xD;
         18. Has evidence of (non-infectious) pneumonitis that required steroids or current&#xD;
             pneumonitis&#xD;
&#xD;
         19. Has a history of interstitial lung disease&#xD;
&#xD;
         20. Has an active infection requiring systemic therapy&#xD;
&#xD;
         21. Has a history or current evidence of any condition, therapy, or laboratory abnormality&#xD;
             that might confound the results of the trial, interfere with the subject's&#xD;
             participation for the full duration of the trial, or is not in the best interest of&#xD;
             the subject to participate, in the opinion of the treating Investigator&#xD;
&#xD;
         22. Has a clinically significant cardiovascular disease such as unstable angina,&#xD;
             myocardial infarction, or acute coronary syndrome within ≤180 days prior to start of&#xD;
             study treatment, symptomatic or uncontrolled arrhythmia, congestive heart failure, or&#xD;
             any Class 3 or 4 cardiac disease as defined by the New York Heart Association&#xD;
             Functional Classification&#xD;
&#xD;
         23. Has a known psychiatric or substance abuse disorder(s) that would interfere with&#xD;
             informed consent or cooperation with the requirements of the trial&#xD;
&#xD;
         24. Is pregnant or breastfeeding, or expecting to conceive or father children within the&#xD;
             projected duration of the trial, starting with the pre-screening or screening visit&#xD;
             through 120 days after the last dose of trial treatment&#xD;
&#xD;
         25. With TNBC has received prior therapy with an anti-PD-1, anti-PD-L1, anti-CTLA-4, or&#xD;
             anti-PD-L2 agent&#xD;
&#xD;
         26. Has received a live-virus vaccination within 30 days of planned treatment start.&#xD;
             Seasonal flu vaccines that do not contain live virus are permitted&#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>Arizona Center for Cancer Care</name>
      <address>
        <city>Avondale</city>
        <state>Arizona</state>
        <zip>85392</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>John Wayne Cancer Institute</name>
      <address>
        <city>Santa Monica</city>
        <state>California</state>
        <zip>90404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado Cancer Center</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Cancer and Blood Center</name>
      <address>
        <city>Athens</city>
        <state>Georgia</state>
        <zip>30607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Piedmont Cancer Institute</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30318</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stony Brook University Cancer Center</name>
      <address>
        <city>Stony Brook</city>
        <state>New York</state>
        <zip>11794</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Thomas Jefferson University Sidney Kimmel Cancer Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Millennium Oncology</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77090</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>November 22, 2016</study_first_submitted>
  <study_first_submitted_qc>November 30, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 5, 2016</study_first_posted>
  <last_update_submitted>March 23, 2021</last_update_submitted>
  <last_update_submitted_qc>March 23, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 25, 2021</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>Breast Neoplasms</mesh_term>
    <mesh_term>Melanoma</mesh_term>
    <mesh_term>Triple Negative Breast Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</mesh_term>
  </intervention_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/NCT02981303
org study id: BT-CL-PGG-MEL/BCA-1621/MK3475
nct id: NCT02981303
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Objective: To determine the Overall Response Rate (ORR) to Imprime PGG + pembrolizumab in
      subjects with advanced melanoma or metastatic TNBC

      Safety: To characterize the safety of Imprime PGG + pembrolizumab given in combination

      Hypothesis: Restore (for melanoma) or enhance (for TNBC) sensitivity to checkpoint inhibitors
      (CPI) by appropriate and effective stimulation of the subject's innate and adaptive immune
      systems in those subjects who have failed 1st line therapy

      The study will incorporate Simon's optimal 2-stage design with sample size fixed at 12
      subjects each in Stage 1 for advanced melanoma and for Triple Negative Breast Cancer (TNBC)
      subjects. The safety criterion of ≤ 4 (or ≤ 33%) subjects with Grade 3/4 adverse events in
      Cycle 1 within either tumor type must be met in order to proceed to Stage 2. The starting
      dose is 4 mg/kg for Imprime PGG. In the event there are a total of > 4 (or > 33%) of subjects
      with Grade 3/4 adverse events in Cycle 1, the dose of Imprime PGG will be reduced to 2 mg/kg,
      and Stage 1 will be repeated at a dose of 2 mg/kg with an additional cohort of n=12 subjects.
      For the dose that meets the safety criterion in Stage 1, at least 1 response in melanoma
      subjects and 2 responses in TNBC subjects amongst the 12 subjects within each tumor type must
      be observed in order to proceed to Stage 2.

      Stage 2 will enroll an additional 17 subjects with melanoma, and 30 subjects with TNBC. For
      the dose that meets the Stage 1 safety criterion, success will be declared if at least 4
      amongst the total of up to 29 subjects with melanoma, and 13 amongst the total of up to 42
      subjects with TNBC achieve an objective response.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Response Rate (ORR) to Imprime PGG + pembrolizumab using RECIST v1.1 criteria
time frame: Within 18 months of last patient enrolled
measure: Time to response (TTR) using RECIST v1.1 criteria
time frame: Within 24 months of last patient enrolled
measure: Complete response rate (CRR) using RECIST v1.1 criteria
time frame: Within 24 months of last patient enrolled
measure: Duration of overall response (DoR) using RECIST v1.1 criteria
time frame: Within 24 months of last patient enrolled
measure: Progression-Free Survival (PFS) and PFS rate at 6 months and 1 year using RECIST v1.1 criteria
time frame: Within 24 months of last patient enrolled
measure: Overall survival (OS) and OS rate at 1 year using RECIST v1.1 criteria
time frame: Within 24 months of last patient enrolled
measure: Pharmacokinetic (PK) data of Imprime PGG in combination with Pembrolizumab
time frame: Within 24 months of last patient enrolled
description: Correlate serum Imprime PGG concentration/time relationship
measure: ORR based on irRECIST
time frame: Within 24 months of last patient enrolled
measure: PFS based on irRECIST
time frame: Within 24 months of last patient enrolled
measure: Correlate levels of baseline serum anti-β-glucan antibody (ABA) with objective response and treatment outcomes
time frame: Within 24 months of last patient enrolled
measure: Correlate changes in immune cell activation markers, such as CD86 expression in tumor biopsy samples* and in peripheral blood immune cells with objective response and treatment outcome
time frame: Within 24 months of last patient enrolled
measure: In tumor biopsies, correlate changes in the tumor immune microenvironment including TILs (Tumor-infiltrating Lymphocytes) and tumor-infiltrating myeloid cells with objective response and treatment outcome
time frame: Within 24 months of last patient enrolled
measure: Correlate PD-L1 expression in tumor biopsy samples (in tumor cells and myeloid cells) with objective response and treatment outcome
time frame: Within 24 months of last patient enrolled
arm group label: Melanoma
arm group type: Experimental
description: Imprime PGG + Pembrolizumab
arm group label: Triple Negative Breast Cancer
arm group type: Experimental
description: Imprime PGG + Pembrolizumab
intervention type: Biological
intervention name: Imprime PGG
description: Imprime PGG is a soluble, β-1,3/1,6 glucan isolated from the cell wall of a proprietary Saccharomyces cerevisiae yeast strain. Imprime PGG acts as a Pathogen-Associated Molecular Pattern (PAMP). Imprime will be administered at a dose of 4 mg/kg IV over a 2-hour infusion time on Days 1, 8 and 15 of each 3-week treatment cycle.
arm group label: Melanoma
arm group label: Triple Negative Breast Cancer
other name: Imprime
intervention type: Drug
intervention name: Pembrolizumab
description: Pembrolizumab is a humanized monoclonal antibody against the programmed death receptor-1 protein. Pembrolizumab will be given at a fixed dose of 200 mg IV over 30 minutes on Day 1 of each 3-week treatment cycle after the Imprime infusion.
arm group label: Melanoma
arm group label: Triple Negative Breast Cancer
other name: Keytruda
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
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country: United States
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Melanoma
mesh term: Triple Negative Breast Neoplasms
mesh term: Pembrolizumab
sharing ipd: No