<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/NCT03023722</url>
  </required_header>
  <id_info>
    <org_study_id>1608018265</org_study_id>
    <nct_id>NCT03023722</nct_id>
  </id_info>
  <brief_title>Phase II Anetumab Ravtansine in Pre-treated Mesothelin-expressing Pancreatic Cancer</brief_title>
  <official_title>An Open-label, Phase II Study of Intravenous Anetumab Ravtansine (BAY 94-9343), an Anti-mesothelin Antibody Drug Conjugate, in Pretreated Mesothelin-expressing Advanced Pancreatic Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yale University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bayer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Yale University</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>
      The primary objective of this study is to:&#xD;
&#xD;
      -Test the activity/response rate per RECIST 1.1 criteria of anetumab ravtansine in patients&#xD;
      with advanced pancreatic cancer who stain for mesothelin expression&#xD;
&#xD;
      The secondary objectives of this study are to:&#xD;
&#xD;
        -  Time to Progression (TTP) defined as time from study treatment to RECIST 1.1&#xD;
           progression, or death (others going off study will be censored)&#xD;
&#xD;
        -  Toxicity in pancreatic cancer patients (at 6.5 mg/kg dose)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a non-randomized, open-label, multicenter, Phase II study to evaluate the efficacy&#xD;
      and safety of intravenous anetumab ravtansine (BAY 94-9343), an anti-mesothelin antibody drug&#xD;
      conjugate, in pretreated mesothelin-expressing advanced pancreatic cancer.&#xD;
&#xD;
      At the time of the start of study treatment, the patients will have pretreated advanced&#xD;
      pancreatic cancer that also overexpresses mesothelin as determined by immunohistochemistry&#xD;
      (IHC).&#xD;
&#xD;
      A maximum of 30 patients will be enrolled in a minimax, Simon 2-stage design with a single&#xD;
      early stopping rule for lack of efficacy. The target population is those patients with&#xD;
      pancreatic cancer who have failed an earlier treatment. All patients will be treated with an&#xD;
      anti-mesothelin immuno-conjugate, in this single arm, non-randomized trial and all patients&#xD;
      treated with at least one dose of Anetumab will be included. The endpoint is any response&#xD;
      using the RECIST 1.1 criteria.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 11, 2017</start_date>
  <completion_date type="Actual">December 11, 2019</completion_date>
  <primary_completion_date type="Actual">August 6, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Response Rate as Measured Per RECIST 1.1 Criteria</measure>
    <time_frame>From start of treatment until disease progression or death (up to 3 years).</time_frame>
    <description>Primary efficacy will be assessed based on radiological tumor evaluation by contrast-enhanced computed tomography (CT) or contrast-enhanced magnetic resonance imaging (MRI) of chest/abdomen/pelvis. Contrast enhanced RECIST 1.1 scan will be done at Prescreening. Said pre-screen scan will be the baseline measure. RECIST 1.1 Scans will be done every 6 weeks for the first 6 months after the start of treatment, or more frequently if clinically indicated, every 9 weeks until the end of year 2 and every 12 weeks thereafter until disease progression or end of study, whichever comes first.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to Progression</measure>
    <time_frame>From start of treatment until disease progression or death (up to 3 years).</time_frame>
    <description>Time to Progression (TTP) defined as time from study treatment to RECIST progression, or death (others going off study will be censored).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Drug Toxicity</measure>
    <time_frame>From start of treatment until disease progression or death (up to 3 years).</time_frame>
    <description>Toxicity of Anetumab ravtansine assessed with National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. See adverse events for details. Participants who experienced any adverse events are included here.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Pancreatic Cancer</condition>
  <arm_group>
    <arm_group_label>All Subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with advanced metastatic pancreatic cancer who have measurable disease</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>anetumab ravtansine</intervention_name>
    <description>Patients will receive anetumab ravtansine IV infusion at a dose of 6.5 mg/kg (recommended Phase II dose) on Day 1 of a 21-day cycle</description>
    <arm_group_label>All Subjects</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Eligibility criteria for prescreening&#xD;
&#xD;
          -  Must have had at least one and not more than two prior chemotherapy regimens for&#xD;
             advanced disease (neoadjuvant or adjuvant chemotherapy would not be counted as a line&#xD;
             of therapy). If prior radiation, measurable lesion outside radiation portal.&#xD;
&#xD;
          -  Written informed consent for prescreening.&#xD;
&#xD;
          -  Unresectable locally advanced or metastatic pancreatic cancer, confirmed by histology&#xD;
&#xD;
          -  Availability of archival or fresh tissue for testing of mesothelin expression level.&#xD;
&#xD;
        Note: Archival tissue is preferred and fresh biopsy should only be obtained if no archival&#xD;
        tissue is available and if in the investigator's judgement, there is no additional risk for&#xD;
        the patient's safety. Patients with a sarcomatoid histology are not expected to have&#xD;
        mesothelin overexpression and should not enter prescreening.&#xD;
&#xD;
          -  Age ≥ 18 years.&#xD;
&#xD;
          -  Life expectancy of at least 3 months.&#xD;
&#xD;
          -  No prior treatment with anetumab ravtansine (or any other mesothelin-based therapy)&#xD;
&#xD;
        Eligibility criteria for full study&#xD;
&#xD;
          -  Written informed consent for full study.&#xD;
&#xD;
          -  Histological documentation of overexpressing mesothelin at the moderate (2+) or&#xD;
             stronger (3+) level in at least 30% of tumor cells as determined by IHC.&#xD;
&#xD;
          -  Unresectable locally advanced or metastatic pancreatic cancer&#xD;
&#xD;
          -  At least one but not more than two prior chemotherapy regimens with progression or&#xD;
             documented intolerance (neoadjuvant or adjuvant chemotherapy would not be counted as a&#xD;
             line of therapy).&#xD;
&#xD;
          -  Patients must have at least 1 measurable lesion according to RECIST v 1.1&#xD;
&#xD;
          -  ECOG PS of 0 or 1&#xD;
&#xD;
          -  Life expectancy of at least 3 months.&#xD;
&#xD;
          -  Adequate bone marrow, liver and renal function as assessed by the following laboratory&#xD;
             requirements conducted within 7 days before starting study treatment:&#xD;
&#xD;
          -  Total bilirubin ≤ 1.5 x the upper limit of normal (ULN). Documented Gilbert syndrome&#xD;
             is allowed if total bilirubin is mildly elevated (&lt; 6 mg/dL).&#xD;
&#xD;
          -  ALT and AST ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver involvement of their&#xD;
             cancer).&#xD;
&#xD;
          -  ALP limit ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver involvement of their cancer).&#xD;
&#xD;
          -  Extent of baseline tumor burden will not interfere with causal assessment of&#xD;
             treatment-emergent hepatotoxicity, at the investigator's discretion.&#xD;
&#xD;
          -  Amylase and lipase ≤ 1.5 x ULN.&#xD;
&#xD;
          -  Glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m2 according to the Modification of&#xD;
             Diet in Renal Disease (MDRD) abbreviated formula (see Appendix 16.6).&#xD;
&#xD;
          -  Adequate coagulation, as assessed by the following laboratory test results:&#xD;
&#xD;
          -  International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN (CTCAE Grade&#xD;
             ≤ 1).&#xD;
&#xD;
          -  Partial thromboplastin time (PTT) or activated PTT (aPTT) ≤ 1.5 x ULN (CTCAE Grade ≤&#xD;
             1).&#xD;
&#xD;
        Note: Patients on stable dose of anti-coagulation therapy will be allowed to participate if&#xD;
        they have no sign of bleeding or clotting and INR / PT and PTT / aPTT test results are&#xD;
        compatible with the acceptable benefit-risk ratio at the investigator's discretion&#xD;
&#xD;
          -  Platelet count ≥ 75,000/mm3 , without platelet transfusion within 3 weeks before the&#xD;
             start of study treatment.&#xD;
&#xD;
          -  Hemoglobin (Hb) ≥ 8 g/dL, without blood transfusion or erythropoietin within 6 weeks&#xD;
             before the start of study treatment.&#xD;
&#xD;
        Note: Patients on stable dose of anti-coagulation therapy will be allowed to participate if&#xD;
        they have no sign of bleeding or clotting and INR / PT and PTT / aPTT test results are&#xD;
        compatible with the acceptable benefit-risk ratio at the investigator's discretion (see&#xD;
        Section 8.1).&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) ≥ 1000/mm3&#xD;
&#xD;
          -  Left ventricular ejection fraction (LVEF) ≥ 50% or the lower limit of normal (LLN)&#xD;
             according to local institution ranges of normality&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous assignment to treatment during this study. Patients permanently withdrawn&#xD;
             from study participation will not be allowed to re-enter the study.&#xD;
&#xD;
          -  Previous (within 5 drug half-lives - if drug half-life in subjects is known - or 28&#xD;
             days, whichever is shorter, before the start of study treatment) or concomitant&#xD;
             participation in another clinical study with investigational medicinal product(s)&#xD;
             (IMP[s]).&#xD;
&#xD;
          -  Patients with corneal epitheliopathy or any eye disorder that may predispose the&#xD;
             patients to this condition at the discretion of the investigator.&#xD;
&#xD;
          -  Previous or concurrent cancer that is distinct in primary site or histology within 5&#xD;
             years. Exceptions: curatively treated&#xD;
&#xD;
          -  Cervical cancer in situ.&#xD;
&#xD;
          -  Non-melanoma skin cancer.&#xD;
&#xD;
          -  Superficial bladder tumors (Non-invasive tumor [Ta], Carcinoma in situ [Tis] and Tumor&#xD;
             invades lamina propria [T1]).&#xD;
&#xD;
          -  Major surgery, open biopsy or significant traumatic injury within 28 days before the&#xD;
             start of study treatment.&#xD;
&#xD;
          -  Pregnant or breast-feeding patients. Women of childbearing potential must have a serum&#xD;
             pregnancy test performed a maximum of 7 days before the start of study treatment, and&#xD;
             a negative result must be documented before the start of study treatment.&#xD;
&#xD;
          -  Pre-existing cardiac conditions as outlined below:&#xD;
&#xD;
          -  Congestive heart failure ≥ New York Heart Association (NYHA) class 2.&#xD;
&#xD;
          -  Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3&#xD;
             months). Myocardial infarction less than 6 months before the start of study treatment.&#xD;
&#xD;
          -  Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are&#xD;
             permitted).&#xD;
&#xD;
          -  Clinically significant uncontrolled hypertension (systolic blood pressure &gt; 150 mmHg&#xD;
             or diastolic pressure &gt; 90 mmHg despite optimal medical management).&#xD;
&#xD;
          -  Arterial thrombotic or embolic events such as cerebrovascular accident (including&#xD;
             transient ischemic attacks), or venous pulmonary embolism within 6 months before the&#xD;
             start of study treatment; venous thrombotic events such as deep vein thrombosis within&#xD;
             3 months before the start of study treatment.&#xD;
&#xD;
          -  Ongoing or active infection (bacterial, fungal, or viral) of NCI-CTCAE version 4.03&#xD;
             Grade &gt; 2.&#xD;
&#xD;
          -  Known history of human immunodeficiency virus (HIV) infection.&#xD;
&#xD;
          -  Known history of chronic hepatitis B or C.&#xD;
&#xD;
          -  Patients with seizure disorder requiring medication.&#xD;
&#xD;
          -  Symptomatic brain metastases or meningeal tumors or other uncontrolled metastases in&#xD;
             the central nervous system (CNS) unless the patient&#xD;
&#xD;
          -  Is &gt; 6 months from definitive therapy,&#xD;
&#xD;
          -  Has a negative imaging study within 4 weeks before study entry (ICF signature for full&#xD;
             study) and&#xD;
&#xD;
          -  Is clinically stable with respect to the tumor at the time of study entry.&#xD;
&#xD;
          -  History of organ allograft, stem cells or bone marrow transplant.&#xD;
&#xD;
          -  Patients with evidence or history of bleeding diathesis. Any hemorrhage or bleeding&#xD;
             event ≥ CTCAE Grade 3 within 4 weeks before the start of study treatment.&#xD;
&#xD;
          -  Non-healing wound, ulcer, or bone fracture.&#xD;
&#xD;
          -  Renal failure requiring peritoneal dialysis or hemodialysis.&#xD;
&#xD;
          -  Known hypersensitivity to anetumab ravtansine, study drug classes or excipients in the&#xD;
             formulation.&#xD;
&#xD;
          -  Any illness or medical conditions that are unstable or could jeopardize the safety of&#xD;
             the patient and his/her compliance in the study.&#xD;
&#xD;
          -  Unresolved toxicity higher than NCI-CTCAE version 4.03 Grade 1 attributed to any prior&#xD;
             therapy/procedure excluding anemia or neuropathy Grade 2 and alopecia of any Grade.&#xD;
&#xD;
          -  Any prohibited prior or concomitant therapy&#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>Stacey Stein, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Yale Cancer Center, Yale University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Yale Cancer Center</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06510</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rutgers Cancer Institute of New Jersey</name>
      <address>
        <city>New Brunswick</city>
        <state>New Jersey</state>
        <zip>08901-2163</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt-Ingram Cancer Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>January 13, 2017</study_first_submitted>
  <study_first_submitted_qc>January 13, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 18, 2017</study_first_posted>
  <results_first_submitted>November 5, 2020</results_first_submitted>
  <results_first_submitted_qc>January 4, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">January 22, 2021</results_first_posted>
  <last_update_submitted>October 11, 2021</last_update_submitted>
  <last_update_submitted_qc>October 11, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 28, 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>Pancreatic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Maytansine</mesh_term>
    <mesh_term>Anetumab ravtansine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 19, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/22/NCT03023722/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>All Subjects</title>
          <description>Patients with advanced metastatic pancreatic cancer who have measurable disease&#xD;
anetumab ravtansine: Patients will receive anetumab ravtansine IV infusion at a dose of 6.5 mg/kg (recommended Phase II dose) on Day 1 of a 21-day cycle</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>No follow-up assessment</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>All Subjects</title>
          <description>Patients with advanced metastatic pancreatic cancer who have measurable disease&#xD;
anetumab ravtansine: Patients will receive anetumab ravtansine IV infusion at a dose of 6.5 mg/kg (recommended Phase II dose) on Day 1 of a 21-day cycle</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="18"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>50-59 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>60-69 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>70-79 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>80-89 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Response Rate as Measured Per RECIST 1.1 Criteria</title>
        <description>Primary efficacy will be assessed based on radiological tumor evaluation by contrast-enhanced computed tomography (CT) or contrast-enhanced magnetic resonance imaging (MRI) of chest/abdomen/pelvis. Contrast enhanced RECIST 1.1 scan will be done at Prescreening. Said pre-screen scan will be the baseline measure. RECIST 1.1 Scans will be done every 6 weeks for the first 6 months after the start of treatment, or more frequently if clinically indicated, every 9 weeks until the end of year 2 and every 12 weeks thereafter until disease progression or end of study, whichever comes first.</description>
        <time_frame>From start of treatment until disease progression or death (up to 3 years).</time_frame>
        <population>Of the 18 subjects originally enrolled, the analysis population includes the 14 subjects who completed the study. The original intention was to follow subjects for up to 3 years. However, all subjects died before the three year mark, so the study was concluded on Dec. 11.2019, after 2 years and 7 months.</population>
        <group_list>
          <group group_id="O1">
            <title>All Subjects</title>
            <description>Patients with advanced metastatic pancreatic cancer who have measurable disease&#xD;
anetumab ravtansine: Patients will receive anetumab ravtansine IV infusion at a dose of 6.5 mg/kg (recommended Phase II dose) on Day 1 of a 21-day cycle</description>
          </group>
        </group_list>
        <measure>
          <title>Response Rate as Measured Per RECIST 1.1 Criteria</title>
          <description>Primary efficacy will be assessed based on radiological tumor evaluation by contrast-enhanced computed tomography (CT) or contrast-enhanced magnetic resonance imaging (MRI) of chest/abdomen/pelvis. Contrast enhanced RECIST 1.1 scan will be done at Prescreening. Said pre-screen scan will be the baseline measure. RECIST 1.1 Scans will be done every 6 weeks for the first 6 months after the start of treatment, or more frequently if clinically indicated, every 9 weeks until the end of year 2 and every 12 weeks thereafter until disease progression or end of study, whichever comes first.</description>
          <population>Of the 18 subjects originally enrolled, the analysis population includes the 14 subjects who completed the study. The original intention was to follow subjects for up to 3 years. However, all subjects died before the three year mark, so the study was concluded on Dec. 11.2019, after 2 years and 7 months.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>progressive disease</title>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>stable disease</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Progression</title>
        <description>Time to Progression (TTP) defined as time from study treatment to RECIST progression, or death (others going off study will be censored).</description>
        <time_frame>From start of treatment until disease progression or death (up to 3 years).</time_frame>
        <population>Of the 18 subjects originally enrolled, the analysis population includes the 14 subjects who completed the study. The original intention was to follow subjects for up to 3 years. However, all subjects died before the three year mark, so the study was concluded on Dec. 11.2019, after 2 years and 7 months.</population>
        <group_list>
          <group group_id="O1">
            <title>All Subjects</title>
            <description>Patients with advanced metastatic pancreatic cancer who have measurable disease&#xD;
anetumab ravtansine: Patients will receive anetumab ravtansine IV infusion at a dose of 6.5 mg/kg (recommended Phase II dose) on Day 1 of a 21-day cycle</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Progression</title>
          <description>Time to Progression (TTP) defined as time from study treatment to RECIST progression, or death (others going off study will be censored).</description>
          <population>Of the 18 subjects originally enrolled, the analysis population includes the 14 subjects who completed the study. The original intention was to follow subjects for up to 3 years. However, all subjects died before the three year mark, so the study was concluded on Dec. 11.2019, after 2 years and 7 months.</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="63.5" lower_limit="22" upper_limit="148"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Drug Toxicity</title>
        <description>Toxicity of Anetumab ravtansine assessed with National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. See adverse events for details. Participants who experienced any adverse events are included here.</description>
        <time_frame>From start of treatment until disease progression or death (up to 3 years).</time_frame>
        <population>Detailed results are included under adverse events. The original intention was to follow subjects for up to 3 years. However, all subjects died before the three year mark, so the study was concluded on Dec. 11.2019, after 2 years and 7 months.</population>
        <group_list>
          <group group_id="O1">
            <title>All Subjects</title>
            <description>Patients with advanced metastatic pancreatic cancer who have measurable disease&#xD;
anetumab ravtansine: Patients will receive anetumab ravtansine IV infusion at a dose of 6.5 mg/kg (recommended Phase II dose) on Day 1 of a 21-day cycle</description>
          </group>
        </group_list>
        <measure>
          <title>Drug Toxicity</title>
          <description>Toxicity of Anetumab ravtansine assessed with National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. See adverse events for details. Participants who experienced any adverse events are included here.</description>
          <population>Detailed results are included under adverse events. The original intention was to follow subjects for up to 3 years. However, all subjects died before the three year mark, so the study was concluded on Dec. 11.2019, after 2 years and 7 months.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Serious adverse events</title>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other adverse events</title>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Three years.</time_frame>
      <desc>The original intention was to follow subjects for up to 3 years. However, all subjects died before the three year mark, so the study was concluded on Dec. 11.2019, after 2 years and 7 months.</desc>
      <group_list>
        <group group_id="E1">
          <title>All Subjects</title>
          <description>Patients with advanced metastatic pancreatic cancer who have measurable disease&#xD;
anetumab ravtansine: Patients will receive anetumab ravtansine IV infusion at a dose of 6.5 mg/kg (recommended Phase II dose) on Day 1 of a 21-day cycle</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Blood and Lymphatic System Disorders-other</sub_title>
                <description>Febrile Neutropenia</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Obstruction Gastric</sub_title>
                <description>Obstruction Gastric</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <description>Abdominal Pain</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <description>Ascites</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <description>Constipation</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fever</sub_title>
                <description>Fever</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>General Disorders and administration-other specify Failure to Thrive</sub_title>
                <description>Failure to thrive</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>General Disorders and administration-other specify Death NOS</sub_title>
                <description>Death NOS</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Sepsis</sub_title>
                <description>Sepsis</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Infections and Infestations-other</sub_title>
                <description>Elevated White Blood Count</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Infections and Infestations-Other, specify-Rhinovirus</sub_title>
                <description>Rhino virus</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cognitive Disturbance</sub_title>
                <description>Cognitive Disturbance</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Stroke</sub_title>
                <description>Stroke</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute Kidney Injury</sub_title>
                <description>Acute Kidney Injury</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnea</sub_title>
                <description>Dyspnea</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <description>Hypoxia</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Respiratory Failure (Pleural metastatic PD)</sub_title>
                <description>Respiratory Failure (Pleural metastatic PD)</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Palmar Plantar Erythrodysesthes</sub_title>
                <description>Palmar Plantar Erythrodysesthes</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <description>Hypotension</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <description>Anemia</description>
                <counts group_id="E1" events="12" subjects_affected="8" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Decreased Platelet Count</sub_title>
                <description>Decreased Platelet Count</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Hypertriglyceridemia</sub_title>
                <description>Hyperlipidemia</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <description>Thrombocytopenia</description>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Activated partial thromboplastin time prolonged</sub_title>
                <description>PTT Prolonged</description>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <description>Atrial fibrillation</description>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Atrial flutter</sub_title>
                <description>Atrial flutter</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Electrocardiogram QT corrected interval prolonged</sub_title>
                <description>Prolonged QTC</description>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Left ventricular systolic dysfunction</sub_title>
                <description>Left Ventricular Systolic Dysfunction</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Sick sinus syndrome</sub_title>
                <description>Sick Sinus Syndrome</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Hearing impaired</sub_title>
                <description>Hearing impaired</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred vision</sub_title>
                <description>Blurred Vison</description>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Cataract</sub_title>
                <description>Cataracts</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Dry eye</sub_title>
                <description>Dry Eyes</description>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Eye disorders - Other, specify</sub_title>
                <description>Colorblindness</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Eye pain</sub_title>
                <description>Right eye pain</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Glaucoma</sub_title>
                <description>Glaucoma</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Watering eyes</sub_title>
                <description>Watering Eyes</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <description>Abdominal distention</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <description>Abdominal Pain</description>
                <counts group_id="E1" events="19" subjects_affected="12" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <description>Ascites</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <description>Constipation</description>
                <counts group_id="E1" events="19" subjects_affected="11" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <description>Diarrhea</description>
                <counts group_id="E1" events="16" subjects_affected="10" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <description>Dry Mouth</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <description>Dyspepsia</description>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <description>Flatulence</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Gastroesophageal reflux disease</sub_title>
                <description>GERD</description>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other, specify</sub_title>
                <description>Partial gastric outlet obstruction</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other, specify</sub_title>
                <description>Abdominal hernia</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other, specify</sub_title>
                <description>Mouth sores</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Inguinal hernia</sub_title>
                <description>inguinal hernia</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Malabsorption</sub_title>
                <description>Malabsorption</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <description>Nausea</description>
                <counts group_id="E1" events="18" subjects_affected="9" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Occasional Epigastric Pain</sub_title>
                <description>Occasional Epigastric Pain</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <description>Sinus Tachycardia</description>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Small intestinal obstruction</sub_title>
                <description>small intestinal obstruction</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <description>Vomiting</description>
                <counts group_id="E1" events="13" subjects_affected="9" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <description>Weight Loss</description>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <description>Chills</description>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <description>Edema limbs</description>
                <counts group_id="E1" events="7" subjects_affected="5" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <description>Fatigue</description>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <description>fevers</description>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Irritability</sub_title>
                <description>Irritability</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <description>Non cardiac chest pain</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <description>Pain (back/neck)</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <description>Cold</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infections and infestations - Other, specify</sub_title>
                <description>Oral Thrush</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>URI/ Sinus Symptoms</sub_title>
                <description>URI/ Sinus Symptoms</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <description>Urinary tract infection</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <description>Fall</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <description>Alanine Aminotransferase Elevated</description>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <description>Alkaline Phosphatase Increase</description>
                <counts group_id="E1" events="7" subjects_affected="6" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <description>AST Increase</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <description>Elevated bilirubin</description>
                <counts group_id="E1" events="6" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Cardiac troponin I increased</sub_title>
                <description>cardiac troponin i increased</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Cholesterol high</sub_title>
                <description>High Cholesterol</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <description>Creatinine Increase</description>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>GGT increased</sub_title>
                <description>GGT increased</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Hypercholesterolemia</sub_title>
                <description>Hypercholesterolemia</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Increased LDH</sub_title>
                <description>Increased LDH</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>INR increased</sub_title>
                <description>Elevated INR</description>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Investigations- other, specify</sub_title>
                <description>Elevated LDH</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Lipase</sub_title>
                <description>Lipase</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <description>lymphocyte count decrease</description>
                <counts group_id="E1" events="9" subjects_affected="5" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <description>platelet count decrease</description>
                <counts group_id="E1" events="7" subjects_affected="4" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Serum amylase increased</sub_title>
                <description>Serum Amylase Increased</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <description>WBC Count Decrease</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <description>Anorexia</description>
                <counts group_id="E1" events="14" subjects_affected="11" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <description>Dehydration</description>
                <counts group_id="E1" events="8" subjects_affected="5" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Diabetes</sub_title>
                <description>diabetes</description>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>GOUT</sub_title>
                <description>GOUT</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <description>hyperglycemia</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <description>Hypokalemia</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Hyperuricemia</sub_title>
                <description>Hyperuricemia</description>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <description>Hypoalbuminemia</description>
                <counts group_id="E1" events="6" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <description>Hypocalcemia</description>
                <counts group_id="E1" events="6" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <description>Hypokalemia</description>
                <counts group_id="E1" events="8" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>hypomagnesemia</sub_title>
                <description>Hypomagnesemia</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <description>Hyponatremia</description>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <description>Hypophosphatemia</description>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Metabolism and nutrition disorders - Other, specify</sub_title>
                <description>Decreased appetite</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <description>Arthralgias</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Arthritis</sub_title>
                <description>Arthritis - knees / hands</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <description>Back pain</description>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Generalized muscle weakness</sub_title>
                <description>Generalized muscle weakness</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <description>myalgia</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <description>Dizziness</description>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <description>Dysgeusia</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <description>Headache</description>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Investigations - Other, specify</sub_title>
                <description>Tremors</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Neuropathy</sub_title>
                <description>Neuropathy</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Paresthesia</sub_title>
                <description>Bilateral Hands</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <description>Peripheral Sensory Neuropathy</description>
                <counts group_id="E1" events="12" subjects_affected="8" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <description>Anxiety</description>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <description>Depression</description>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <description>Insomnia</description>
                <counts group_id="E1" events="12" subjects_affected="9" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Psychiatric disorders - Other, specify</sub_title>
                <description>Mood Swings</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <description>Aacute kidney injury</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Bladder Cancer</sub_title>
                <description>Bladder Cancer</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Hematuria</sub_title>
                <description>Hematuria</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Proteinuria</sub_title>
                <description>Proteinuria</description>
                <counts group_id="E1" events="8" subjects_affected="5" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Renal and urinary disorders - Other, specify</sub_title>
                <description>Kidney stone</description>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Urinary frequency</sub_title>
                <description>Urinary Frequency</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Urinary retention</sub_title>
                <description>urinary retention</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic rhinitis</sub_title>
                <description>Allergic Rhinitis</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <description>Dry Cough</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <description>Cough</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <description>Dyspnea</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Hiccups</sub_title>
                <description>Hiccups</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Hoarseness</sub_title>
                <description>Hoarseness</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <description>Hypoxia</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <description>Mucositis</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <description>Pleural effusion</description>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Sleep apnea</sub_title>
                <description>Sleep apnea</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Sore throat</sub_title>
                <description>Sore Throat</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Basal Cell Carcinoma of Skin</sub_title>
                <description>Basal Cell Carcinoma of Skin</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Erythroderma</sub_title>
                <description>Facial Erythema</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <description>Pruritis</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <description>Rash</description>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <description>Hypertension</description>
                <counts group_id="E1" events="17" subjects_affected="7" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <description>Orthostatic Hypotension</description>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Orthostatic Hypotension</sub_title>
                <description>Orthostatic Hypotension</description>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Premature termination may occur if risk-benefit ratio is unacceptable due to: safety findings, results of parallel clinical studies and results of parallel animal studies AND if the study does not suggest a completion within a reasonable time frame.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Stacey Stein, MD</name_or_title>
      <organization>Yale University</organization>
      <phone>203 737-1600</phone>
      <email>stacey.stein@yale.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03023722
org study id: 1608018265
nct id: NCT03023722
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The primary objective of this study is to:

      -Test the activity/response rate per RECIST 1.1 criteria of anetumab ravtansine in patients
      with advanced pancreatic cancer who stain for mesothelin expression

      The secondary objectives of this study are to:

        -  Time to Progression (TTP) defined as time from study treatment to RECIST 1.1
           progression, or death (others going off study will be censored)

        -  Toxicity in pancreatic cancer patients (at 6.5 mg/kg dose)
This is a non-randomized, open-label, multicenter, Phase II study to evaluate the efficacy
      and safety of intravenous anetumab ravtansine (BAY 94-9343), an anti-mesothelin antibody drug
      conjugate, in pretreated mesothelin-expressing advanced pancreatic cancer.

      At the time of the start of study treatment, the patients will have pretreated advanced
      pancreatic cancer that also overexpresses mesothelin as determined by immunohistochemistry
      (IHC).

      A maximum of 30 patients will be enrolled in a minimax, Simon 2-stage design with a single
      early stopping rule for lack of efficacy. The target population is those patients with
      pancreatic cancer who have failed an earlier treatment. All patients will be treated with an
      anti-mesothelin immuno-conjugate, in this single arm, non-randomized trial and all patients
      treated with at least one dose of Anetumab will be included. The endpoint is any response
      using the RECIST 1.1 criteria.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Response Rate as Measured Per RECIST 1.1 Criteria
time frame: From start of treatment until disease progression or death (up to 3 years).
description: Primary efficacy will be assessed based on radiological tumor evaluation by contrast-enhanced computed tomography (CT) or contrast-enhanced magnetic resonance imaging (MRI) of chest/abdomen/pelvis. Contrast enhanced RECIST 1.1 scan will be done at Prescreening. Said pre-screen scan will be the baseline measure. RECIST 1.1 Scans will be done every 6 weeks for the first 6 months after the start of treatment, or more frequently if clinically indicated, every 9 weeks until the end of year 2 and every 12 weeks thereafter until disease progression or end of study, whichever comes first.
measure: Time to Progression
time frame: From start of treatment until disease progression or death (up to 3 years).
description: Time to Progression (TTP) defined as time from study treatment to RECIST progression, or death (others going off study will be censored).
measure: Drug Toxicity
time frame: From start of treatment until disease progression or death (up to 3 years).
description: Toxicity of Anetumab ravtansine assessed with National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. See adverse events for details. Participants who experienced any adverse events are included here.
arm group label: All Subjects
arm group type: Experimental
description: Patients with advanced metastatic pancreatic cancer who have measurable disease
intervention type: Drug
intervention name: anetumab ravtansine
description: Patients will receive anetumab ravtansine IV infusion at a dose of 6.5 mg/kg (recommended Phase II dose) on Day 1 of a 21-day cycle
arm group label: All Subjects
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Stacey Stein, MD
role: Principal Investigator
affiliation: Yale Cancer Center, Yale University
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Pancreatic Neoplasms
mesh term: Maytansine
mesh term: Anetumab ravtansine
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Premature termination may occur if risk-benefit ratio is unacceptable due to: safety findings, results of parallel clinical studies and results of parallel animal studies AND if the study does not suggest a completion within a reasonable time frame.
point of contact: 