<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/NCT03258398</url>
  </required_header>
  <id_info>
    <org_study_id>eFT508-0006</org_study_id>
    <nct_id>NCT03258398</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate eFT508 Alone and in Combination With Avelumab in Subjects With MSS Colorectal Cancer</brief_title>
  <official_title>A Phase 2, Open-Label, Randomized, Non-Comparative Study With Preliminary Dose Finding to Evaluate eFT508 Monotherapy or eFT508 in Combination With Avelumab in Subjects With Microsatellite Stable Relapsed or Refractory Colorectal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Effector Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck KGaA, Darmstadt, Germany</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Effector Therapeutics</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase 2, open-label, 2-part, multicenter study in subjects with MSS&#xD;
      relapsed/refractory colorectal cancer. The primary objective of Part 1 is to evaluate the&#xD;
      safety and tolerability of escalating doses of eFT508 in combination with a fixed dose of&#xD;
      avelumab to determine the maximum tolerated dose (MTD) of eFT508 and to select a recommended&#xD;
      dose for Part 2. The primary objective of Part 2 is to evaluate antitumor activity of eFT508&#xD;
      at the recommended dose in combination with avelumab or eFT508 monotherapy. Parts 1 and 2&#xD;
      will also evaluate pharmacokinetics (PK) and pharmacodynamics.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 18, 2017</start_date>
  <completion_date type="Actual">May 13, 2019</completion_date>
  <primary_completion_date type="Actual">March 26, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>In Part 1, subjects will receive eFT508 in combination with a fixed dose of avelumab. Once the recommended dose of eFT508 in combination with avelumab is determined in Part 1, enrollment in Part 2 will begin. Subjects will be randomized in approximately a 2:1 ratio to receive eFT508 in combination with avelumab or eFT508 monotherapy.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Part 1: Proportion of subjects with a dose limiting toxicity (DLT) during the first treatment cycle</measure>
    <time_frame>28 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2: Overall Response Rate</measure>
    <time_frame>8-16 weeks</time_frame>
    <description>the proportion of subjects whose best overall response is a complete or partial response</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">56</enrollment>
  <condition>Microsatellite Stable Relapsed or Refractory Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>Part 1: eFT508 plus avelumab dose finding Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>subjects will receive eFT508 in combination with a fixed dose of avelumab</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2: eFT508 plus avelumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>subjects will receive eFT508 in combination with a fixed dose of avelumab</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2: eFT508 alone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>subjects will receive eFT508 alone</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>eFT508</intervention_name>
    <description>eFT508 will be taken orally (PO) twice a day (bid).</description>
    <arm_group_label>Part 1: eFT508 plus avelumab dose finding Arm</arm_group_label>
    <arm_group_label>Part 2: eFT508 alone</arm_group_label>
    <arm_group_label>Part 2: eFT508 plus avelumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Avelumab</intervention_name>
    <description>Avelumab 10 mg/kg will be administered intravenously (IV) on Day 1 and once every 2 weeks (q2wk) thereafter</description>
    <arm_group_label>Part 1: eFT508 plus avelumab dose finding Arm</arm_group_label>
    <arm_group_label>Part 2: eFT508 plus avelumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ECOG performance status of 0, 1, or 2&#xD;
&#xD;
          -  Pathologically documented diagnosis of colorectal adenocarcinoma.&#xD;
&#xD;
          -  Progressed on or intolerant of at least 2 prior cancer therapy regimens administered&#xD;
             for metastatic disease.&#xD;
&#xD;
          -  Completion of all previous therapy (including surgery, radiotherapy, chemotherapy,&#xD;
             immunotherapy, or investigational therapy) for the treatment of cancer ≥3 weeks before&#xD;
             the start of study therapy.&#xD;
&#xD;
          -  Part 2 only: Presence of radiographically measurable disease (defined as the presence&#xD;
             of ≥1 lesion that measures ≥10 mm [≥15 mm for lymph nodes]). Measurable disease that&#xD;
             was previously radiated is only permitted if progressing.&#xD;
&#xD;
          -  Agrees to undergo a pretreatment and a post-treatment biopsy.&#xD;
&#xD;
          -  Microsatellite stable disease determined by IHC and/or polymerase chain reaction&#xD;
             (PCR).&#xD;
&#xD;
          -  Adequate bone marrow function&#xD;
&#xD;
          -  Adequate hepatic function&#xD;
&#xD;
          -  Adequate renal function&#xD;
&#xD;
          -  Normal coagulation profile&#xD;
&#xD;
          -  Negative antiviral serology&#xD;
&#xD;
          -  Female subjects of childbearing potential must not be pregnant or breastfeeding&#xD;
&#xD;
          -  Willingness to use protocol-recommended methods of contraception or to abstain from&#xD;
             heterosexual intercourse from start of therapy until at lest 30 days after the last&#xD;
             dose of study therapy&#xD;
&#xD;
          -  Life expectancy of ≥3 months.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of another malignancy except for adequately treated local basal cell or&#xD;
             squamous cell carcinoma of the skin; in situ cervical or breast carcinoma; adequately&#xD;
             treated, papillary, noninvasive bladder cancer; other adequately treated Stage 1 or 2&#xD;
             cancers currently in complete remission, or any other cancer that has been in complete&#xD;
             remission for ≥2 years.&#xD;
&#xD;
          -  Known symptomatic brain metastases requiring ≥10 mg/day of prednisolone (or its&#xD;
             equivalent).&#xD;
&#xD;
          -  Significant cardiovascular disease.&#xD;
&#xD;
          -  Significant screening ECG abnormalities.&#xD;
&#xD;
          -  Active autoimmune disease that might deteriorate when receiving an immunostimulatory&#xD;
             agent.&#xD;
&#xD;
          -  Known history of colitis, inflammatory bowel disease, pneumonitis, or pulmonary&#xD;
             fibrosis.&#xD;
&#xD;
          -  Ongoing risk for bleeding due to active peptic ulcer disease or bleeding diathesis.&#xD;
&#xD;
          -  Evidence of an ongoing systemic bacterial, fungal, or viral infection.&#xD;
&#xD;
          -  Any condition that may impact the subject's ability to swallow oral medications.&#xD;
&#xD;
          -  Major surgery within 4 weeks before the start of study therapy.&#xD;
&#xD;
          -  Prior solid organ or bone marrow progenitor cell transplantation.&#xD;
&#xD;
          -  Prior therapy with any known inhibitor of MNK-1 or MNK-2.&#xD;
&#xD;
          -  Prior therapy with any of the following: PD-1, PD-L1, CTLA4 antibody, or any other&#xD;
             drug targeting T cell checkpoint pathways.&#xD;
&#xD;
          -  Prior high dose chemotherapy requiring stem cell rescue.&#xD;
&#xD;
          -  Intolerance to or prior severe (≥Grade 3) allergic or anaphylactic reaction to infused&#xD;
             antibodies or infused therapeutic proteins.&#xD;
&#xD;
          -  Vaccination within 4 weeks of the first dose of avelumab and while on study.&#xD;
&#xD;
          -  Ongoing immunosuppressive therapy.&#xD;
&#xD;
          -  Use of a strong inhibitor or inducer of cytochrome P450 3A4 (CYP3A4) within 7 days&#xD;
             prior to the start of study therapy or expected requirement for use of a strong CYP3A4&#xD;
             inhibitor or inducer during study therapy.&#xD;
&#xD;
          -  Previously received investigational product in a clinical trial within 30 days or&#xD;
             within 5 elimination half lives (whichever is longer) prior to the start of study&#xD;
             therapy, or is planning to take part in another clinical trial while participating in&#xD;
             this study.&#xD;
&#xD;
          -  Has any illness, medical condition, organ system dysfunction, or social situation,&#xD;
             including mental illness or substance abuse, deemed by the Investigator to be likely&#xD;
             to interfere with a subject's ability to sign informed consent, adversely affect the&#xD;
             subject's ability to cooperate and participate in the study, or compromise the&#xD;
             interpretation of study results&#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>Jeremy Barton, MD</last_name>
    <role>Study Director</role>
    <affiliation>CMO</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85259</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute at HealthONE</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80218</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>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kansas City Research Institute</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64131</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>MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>August 21, 2017</study_first_submitted>
  <study_first_submitted_qc>August 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 23, 2017</study_first_posted>
  <last_update_submitted>July 16, 2019</last_update_submitted>
  <last_update_submitted_qc>July 16, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 18, 2019</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>Colorectal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Avelumab</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/NCT03258398
org study id: eFT508-0006
nct id: NCT03258398
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase 2, open-label, 2-part, multicenter study in subjects with MSS
      relapsed/refractory colorectal cancer. The primary objective of Part 1 is to evaluate the
      safety and tolerability of escalating doses of eFT508 in combination with a fixed dose of
      avelumab to determine the maximum tolerated dose (MTD) of eFT508 and to select a recommended
      dose for Part 2. The primary objective of Part 2 is to evaluate antitumor activity of eFT508
      at the recommended dose in combination with avelumab or eFT508 monotherapy. Parts 1 and 2
      will also evaluate pharmacokinetics (PK) and pharmacodynamics.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: In Part 1, subjects will receive eFT508 in combination with a fixed dose of avelumab. Once the recommended dose of eFT508 in combination with avelumab is determined in Part 1, enrollment in Part 2 will begin. Subjects will be randomized in approximately a 2:1 ratio to receive eFT508 in combination with avelumab or eFT508 monotherapy.
primary purpose: Treatment
masking: None (Open Label)
measure: Part 1: Proportion of subjects with a dose limiting toxicity (DLT) during the first treatment cycle
time frame: 28 days
measure: Part 2: Overall Response Rate
time frame: 8-16 weeks
description: the proportion of subjects whose best overall response is a complete or partial response
arm group label: Part 1: eFT508 plus avelumab dose finding Arm
arm group type: Experimental
description: subjects will receive eFT508 in combination with a fixed dose of avelumab
arm group label: Part 2: eFT508 plus avelumab
arm group type: Experimental
description: subjects will receive eFT508 in combination with a fixed dose of avelumab
arm group label: Part 2: eFT508 alone
arm group type: Experimental
description: subjects will receive eFT508 alone
intervention type: Drug
intervention name: eFT508
description: eFT508 will be taken orally (PO) twice a day (bid).
arm group label: Part 1: eFT508 plus avelumab dose finding Arm
arm group label: Part 2: eFT508 alone
arm group label: Part 2: eFT508 plus avelumab
intervention type: Drug
intervention name: Avelumab
description: Avelumab 10 mg/kg will be administered intravenously (IV) on Day 1 and once every 2 weeks (q2wk) thereafter
arm group label: Part 1: eFT508 plus avelumab dose finding Arm
arm group label: Part 2: eFT508 plus avelumab
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jeremy Barton, MD
role: Study Director
affiliation: CMO
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Avelumab
sharing ipd: No