<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/NCT03775850</url>
  </required_header>
  <id_info>
    <org_study_id>EDP1503-101</org_study_id>
    <secondary_id>KEYNOTE-939</secondary_id>
    <nct_id>NCT03775850</nct_id>
  </id_info>
  <brief_title>A Study of EDP1503 in Patients With Colorectal Cancer, Breast Cancer, and Checkpoint Inhibitor Relapsed Tumors</brief_title>
  <official_title>A Phase I Open-label Study of EDP1503 Alone and in Combination With Pembrolizumab in Patients With Advanced Metastatic Colorectal Carcinoma, Triple-negative Breast Cancer, and Checkpoint Inhibitor Relapsed Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Evelo Biosciences, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>SCRI Development Innovations, LLC</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Evelo Biosciences, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</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 study is being conducted to assess the safety, tolerability, and efficacy of EDP1503&#xD;
      alone and in combination with pembrolizumab in patients with advanced metastatic colorectal&#xD;
      carcinoma, triple-negative breast cancer, and checkpoint inhibitor relapsed tumors&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This will be a Phase I open-label study which will involve a 2-week monotherapy with EDP1503,&#xD;
      following which the patients will be dosed with a combination of EDP1503 and pembrolizumab.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 19, 2018</start_date>
  <completion_date type="Actual">October 31, 2021</completion_date>
  <primary_completion_date type="Actual">June 30, 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Patients will be assigned to one of three cohorts based on disease condition: Cohort A (microsatellite stable colorectal cancer); Cohort B (Triple negative breast cancer); Cohort C (PD-1 relapsed tumors: non small cell lung cancer, gastroesophageal cancer, or any microsatellite unstable or renal cell carcinoma). Patients will receive monotherapy with EDP1503 for a period of 2 weeks, following which they will be dosed with a combination of EDP1503 and pembrolizumab.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety and tolerability of EDP1503 alone and in combination with pembrolizumab as assessed per CTCAE v5.0</measure>
    <time_frame>2 years</time_frame>
    <description>Number of participants with EPD1503 related adverse events as assessed per CTCAE v5.0</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and tolerability of EDP1503 alone and in combination with pembrolizumab</measure>
    <time_frame>2 years</time_frame>
    <description>Safety and tolerability of EDP1503 alone and in combination with pembrolizumab assessed via clinical laboratory evaluations</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Evidence of anti-tumor activity of EDP1503 based on ORR</measure>
    <time_frame>2 years</time_frame>
    <description>To determine preliminary evidence of anti-tumor activity of EDP1503 in patients</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>2 years</time_frame>
    <description>Progression Free Survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>2 years</time_frame>
    <description>Overall Survival</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">69</enrollment>
  <condition>Colorectal Cancer Metastatic</condition>
  <condition>Triple Negative Breast Cancer</condition>
  <condition>Non Small Cell Lung Cancer</condition>
  <condition>Bladder Cancer</condition>
  <condition>GastroEsophageal Cancer</condition>
  <condition>Renal Cell Carcinoma</condition>
  <condition>MSI-H</condition>
  <arm_group>
    <arm_group_label>Cohort A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cohort A includes patients with microsatellite stable (MSS) colorectal cancer (CRC). Patients will receive a 14 day run-in of EDP1503 alone, following which they will be treated with a combination of EDP1503 and pembrolizumab.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cohort B includes patients with Triple Negative Breast Cancer (TNBC). Patients will receive a 14 day run-in of EDP1503 alone, following which they will be treated with a combination of EDP1503 and pembrolizumab.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cohort C includes patients with non-small-cell lung cancer (NSCLC), bladder cancer; gastroesophageal (GE) cancer, any microsatellite unstable, or renal cell carcinoma (RCC) who are relapsed to prior PD-1/L1 therapy. Patients will receive a 14 day run-in of EDP1503 alone, following which they will be treated with a combination of EDP1503 and pembrolizumab.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>EDP1503</intervention_name>
    <description>4 capsules taken by mouth twice daily. Each capsule will contain ≥ 7.5x10^10 colony-forming units (CFU)</description>
    <arm_group_label>Cohort A</arm_group_label>
    <arm_group_label>Cohort B</arm_group_label>
    <arm_group_label>Cohort C</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>200 mg given by intravenous (IV) infusion once every 3 weeks</description>
    <arm_group_label>Cohort A</arm_group_label>
    <arm_group_label>Cohort B</arm_group_label>
    <arm_group_label>Cohort C</arm_group_label>
    <other_name>Keytruda</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Selected Inclusion Criteria:&#xD;
&#xD;
          1. Subjects with histologically or cytologically confirmed advanced or metastatic solid&#xD;
             tumors who have had disease progression after treatment with all available therapies&#xD;
             for metastatic disease that are known to confer clinical benefit, or are intolerant to&#xD;
             treatment, or refuse standard treatment.&#xD;
&#xD;
          2. Have adequate organ function as defined in the clinical protocol. Specimens must be&#xD;
             collected within 10 days prior to the start of study treatment.&#xD;
&#xD;
          3. Have provided an archival tumor tissue sample obtained since the most recent prior&#xD;
             anticancer regimen or newly obtained core or excisional biopsy of a tumor lesion not&#xD;
             previously irradiated.&#xD;
&#xD;
          4. Measurable disease by RECIST v1.1 as assessed by the local site&#xD;
             investigator/radiologist. Lesions situated in a previously irradiated area are&#xD;
             considered measurable if progression has been demonstrated in such lesions.&#xD;
&#xD;
          5. Metastatic disease not suitable for upfront curative-intent surgery.&#xD;
&#xD;
          6. Progressive disease on previous line of therapy per treating investigator (additional&#xD;
             specific criteria for cohort C).&#xD;
&#xD;
          7. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.&#xD;
&#xD;
          8. Additional tumor-specific inclusion criteria&#xD;
&#xD;
        Selected Exclusion Criteria:&#xD;
&#xD;
          1. Has received prior radiotherapy within 2 weeks of start of study treatment. Patients&#xD;
             must have recovered from all radiation-related toxicities, not require&#xD;
             corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted&#xD;
             for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.&#xD;
&#xD;
          2. Treatment with investigational therapy within 28 days prior to initiation of study&#xD;
             treatment.&#xD;
&#xD;
          3. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with&#xD;
             an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g.,&#xD;
             CTLA-4, OX40, CD137) and was discontinued from that treatment due to a Grade 3 or&#xD;
             higher immune-related adverse event (irAE).&#xD;
&#xD;
          4. Has received prior systemic anti-cancer therapy within 28 days or 5 half-lives,&#xD;
             whichever is shorter prior to treatment.&#xD;
&#xD;
             Note: Patients must have recovered from all AEs due to previous therapies to ≤Grade 1&#xD;
             or baseline. Patients with ≤Grade 2 neuropathy may be eligible.&#xD;
&#xD;
             Note: If patient received major surgery, they must have recovered adequately from the&#xD;
             toxicity and/or complications from the intervention prior to starting study treatment.&#xD;
&#xD;
          5. Impaired cardiac function or clinically significant cardiac diseases, including any of&#xD;
             the following:&#xD;
&#xD;
               1. Unstable angina or acute myocardial infarction ≤ 3 months prior to C1D1;&#xD;
&#xD;
               2. Clinically significant heart disease (e.g., symptomatic congestive heart failure&#xD;
                  [e.g., &gt;NYHA Class 2]; uncontrolled arrhythmia, or hypertension; history of&#xD;
                  labile hypertension or poor compliance with an antihypertensive regimen).&#xD;
&#xD;
          6. Uncontrolled active severe systemic infection requiring parenteral antibiotics within&#xD;
             1 week, and systemic antivirals or antifungals within two weeks prior to C1D1.&#xD;
&#xD;
          7. Patients with active CNS metastases and/or carcinomatous meningitis. Patients with&#xD;
             previously treated brain metastases may participate provided they are radiologically&#xD;
             stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging&#xD;
             (note that the repeat imaging should be performed during study screening), clinically&#xD;
             stable and without requirement of steroid treatment for at least 14 days prior to&#xD;
             first dose of study treatment.&#xD;
&#xD;
          8. Patients with severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its&#xD;
             excipients.&#xD;
&#xD;
          9. Prior malignancies:&#xD;
&#xD;
               1. Patients with adequately resected basal or squamous cell carcinoma of the skin,&#xD;
                  or adequately resected carcinoma in situ (i.e. cervix, breast) may enroll&#xD;
                  irrespective of the time of diagnosis.&#xD;
&#xD;
               2. Patients with a known additional malignancy that is progressing or has required&#xD;
                  active treatment within the past which may interfere with the interpretation of&#xD;
                  the study. Cancer treated with curative intent &lt; 5 years previously will not be&#xD;
                  allowed unless approved by the Sponsor. Cancer treated with curative intent &gt; 5&#xD;
                  years previously and without evidence of recurrence will be allowed.&#xD;
&#xD;
         10. Patients with a diagnosis of immunodeficiency or receiving chronic systemic steroid&#xD;
             therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form&#xD;
             of immunosuppressive therapy within 7 days prior the first dose of study drug.&#xD;
&#xD;
         11. Patients with uncontrolled vomiting or dirrahea that could interfere with the GI&#xD;
             exposure to EDP1503.&#xD;
&#xD;
         12. Patients who are transfusion dependent should be discussed with the Medical Monitor&#xD;
&#xD;
         13. Patients unwilling to comply with the protocol including required biopsies and sample&#xD;
             collections required to measure disease.&#xD;
&#xD;
         14. Has active autoimmune disease that has required systemic treatment in the past 2 years&#xD;
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive&#xD;
             drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid&#xD;
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a&#xD;
             form of systemic treatment.&#xD;
&#xD;
         15. Has received a live vaccine within 30 days of planned C1D1. Note: Examples of live&#xD;
             vaccines include, but are not limited to, the following: measles, mumps, rubella,&#xD;
             varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG),&#xD;
             and typhoid vaccine. Seasonal influenza vaccines for injection are generally&#xD;
             inactivated flu vaccines and are allowed. Intranasal influenza vaccines (e.g FluMist)&#xD;
             are live attenuated vaccines and are not allowed.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Johanna Bendell, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>SCRI Development Innovations, LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Highlands Oncology Group</name>
      <address>
        <city>Rogers</city>
        <state>Arkansas</state>
        <zip>72758</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists</name>
      <address>
        <city>Sarasota</city>
        <state>Florida</state>
        <zip>34232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stephenson Cancer Center</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tennessee Oncology, PLLC</name>
      <address>
        <city>Chattanooga</city>
        <state>Tennessee</state>
        <zip>37404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tennessee Oncology</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre de Recherche du CHUM</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H2X 0A9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jewish General Hospital</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H3T1E2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Québec - Université Laval</name>
      <address>
        <city>Québec</city>
        <zip>G1R 2J6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>December 12, 2018</study_first_submitted>
  <study_first_submitted_qc>December 12, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 14, 2018</study_first_posted>
  <last_update_submitted>March 22, 2023</last_update_submitted>
  <last_update_submitted_qc>March 22, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 24, 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>Carcinoma</mesh_term>
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Colorectal Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Renal Cell</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/NCT03775850
org study id: EDP1503-101
secondary id: KEYNOTE-939
nct id: NCT03775850
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study is being conducted to assess the safety, tolerability, and efficacy of EDP1503
      alone and in combination with pembrolizumab in patients with advanced metastatic colorectal
      carcinoma, triple-negative breast cancer, and checkpoint inhibitor relapsed tumors
This will be a Phase I open-label study which will involve a 2-week monotherapy with EDP1503,
      following which the patients will be dosed with a combination of EDP1503 and pembrolizumab.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: Patients will be assigned to one of three cohorts based on disease condition: Cohort A (microsatellite stable colorectal cancer); Cohort B (Triple negative breast cancer); Cohort C (PD-1 relapsed tumors: non small cell lung cancer, gastroesophageal cancer, or any microsatellite unstable or renal cell carcinoma). Patients will receive monotherapy with EDP1503 for a period of 2 weeks, following which they will be dosed with a combination of EDP1503 and pembrolizumab.
primary purpose: Treatment
masking: None (Open Label)
measure: Safety and tolerability of EDP1503 alone and in combination with pembrolizumab as assessed per CTCAE v5.0
time frame: 2 years
description: Number of participants with EPD1503 related adverse events as assessed per CTCAE v5.0
measure: Safety and tolerability of EDP1503 alone and in combination with pembrolizumab
time frame: 2 years
description: Safety and tolerability of EDP1503 alone and in combination with pembrolizumab assessed via clinical laboratory evaluations
measure: Evidence of anti-tumor activity of EDP1503 based on ORR
time frame: 2 years
description: To determine preliminary evidence of anti-tumor activity of EDP1503 in patients
measure: Progression Free Survival
time frame: 2 years
description: Progression Free Survival
measure: Overall Survival
time frame: 2 years
description: Overall Survival
arm group label: Cohort A
arm group type: Experimental
description: Cohort A includes patients with microsatellite stable (MSS) colorectal cancer (CRC). Patients will receive a 14 day run-in of EDP1503 alone, following which they will be treated with a combination of EDP1503 and pembrolizumab.
arm group label: Cohort B
arm group type: Experimental
description: Cohort B includes patients with Triple Negative Breast Cancer (TNBC). Patients will receive a 14 day run-in of EDP1503 alone, following which they will be treated with a combination of EDP1503 and pembrolizumab.
arm group label: Cohort C
arm group type: Experimental
description: Cohort C includes patients with non-small-cell lung cancer (NSCLC), bladder cancer; gastroesophageal (GE) cancer, any microsatellite unstable, or renal cell carcinoma (RCC) who are relapsed to prior PD-1/L1 therapy. Patients will receive a 14 day run-in of EDP1503 alone, following which they will be treated with a combination of EDP1503 and pembrolizumab.
intervention type: Biological
intervention name: EDP1503
description: 4 capsules taken by mouth twice daily. Each capsule will contain ≥ 7.5x10^10 colony-forming units (CFU)
arm group label: Cohort A
arm group label: Cohort B
arm group label: Cohort C
intervention type: Biological
intervention name: Pembrolizumab
description: 200 mg given by intravenous (IV) infusion once every 3 weeks
arm group label: Cohort A
arm group label: Cohort B
arm group label: Cohort C
other name: Keytruda
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Johanna Bendell, MD
role: Principal Investigator
affiliation: SCRI Development Innovations, LLC
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Canada
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Breast Neoplasms
mesh term: Colorectal Neoplasms
mesh term: Carcinoma, Renal Cell
mesh term: Triple Negative Breast Neoplasms
mesh term: Pembrolizumab
sharing ipd: No