<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/NCT03267316</url>
  </required_header>
  <id_info>
    <org_study_id>CAN04CLIN001</org_study_id>
    <secondary_id>2017-001111-36</secondary_id>
    <nct_id>NCT03267316</nct_id>
  </id_info>
  <brief_title>A First-in-Human Study of CAN04 in Patients With Solid Malignant Tumors</brief_title>
  <acronym>CANFOUR</acronym>
  <official_title>An Open Label, Dose Escalation Followed by Dose Expansion, Safety and Tolerability Trial of CAN04, a Fully Humanized Monoclonal Antibody Against IL1RAP, in Subjects With Solid Malignant Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cantargia AB</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cantargia AB</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will evaluate the safety, tolerability, and preliminary antitumor activity of&#xD;
      CAN04 both as a monotherapy and in combination with standard of care treatment in subjects&#xD;
      with solid cancer tumors.&#xD;
&#xD;
      Following completion of the first part, the dose escalation cohorts, and determination of&#xD;
      maximum tolerated dose or recommended phase 2 dose (MTD/RP2D), safety and tolerability will&#xD;
      be further evaluated in an expanded cohort of subjects with pancreatic or lung cancer, as&#xD;
      monotherapy or in combination with the standard of care treatment, to identify the RP2D of&#xD;
      CAN04 in combination with standard of care. In addition, early signs of efficacy during&#xD;
      treatment with CAN04 will be investigated.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      CAN04 is a first-in-class fully humanized and ADCC enhanced monoclonal antibody, targeting&#xD;
      the Interleukin 1 Receptor Accessory Protein (IL1RAP).&#xD;
&#xD;
      The CAN04 strategy is to attack the IL1RAP target molecule using an effective antibody-based&#xD;
      cancer treatment. In preclinical (in vitro and in vivo) studies, CAN04 has shown two distinct&#xD;
      mechanisms of action:&#xD;
&#xD;
        1. By blocking the intracellular signals from the IL1RAP target molecule, thereby impairing&#xD;
           the cancer cells' ability to secrete tumor stimulating cytokines, in turn reducing tumor&#xD;
           inflammation and tumor progression.&#xD;
&#xD;
        2. Through antibody dependent cellular cytotoxicity (ADCC) against IL1RAP expressing tumor&#xD;
           cells where CAN04 stimulates natural killer (NK) cells to attack the tumor cells.&#xD;
&#xD;
      The study is a combined phase 1/2a, open-label, dose-escalation followed by dose expansion,&#xD;
      safety and tolerability clinical trial, in patients with relapsed or refractory solid tumors.&#xD;
      It consists of two parts.&#xD;
&#xD;
      In Part I (Dose Escalation - DE), the intention is to include patients with any of the four&#xD;
      solid tumor types: Non-Small Cell Lung Cancer (NSCLC), Pancreatic Ductal Adenocarcinoma&#xD;
      (PDAC), Triple Negative Breast Cancer (TNBC) or Colorectal Cancer (CRC). In this part of the&#xD;
      study safety and tolerability will be documented and the MTD/ RP2D will be determined.&#xD;
      Patients will stay on CAN04 treatment until disease progression, unacceptable toxicity, or&#xD;
      discontinuation for any other reason. [Completed December 2018]&#xD;
&#xD;
      In Part II (Expansion Cohort - EC), safety and tolerability will be further evaluated in an&#xD;
      expanded cohort of subjects with PDAC or NSCLC at the RP2D level. In addition, early signs of&#xD;
      efficacy during treatment with CAN04 will be investigated, as monotherapy or in combination&#xD;
      with the standard of care.&#xD;
&#xD;
      Patients will stay on treatment until disease progression, unacceptable toxicity, or&#xD;
      discontinuation for any other reason. [Enrollment to monotherapy arms completed]&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">September 19, 2017</start_date>
  <completion_date type="Anticipated">October 2022</completion_date>
  <primary_completion_date type="Anticipated">March 2022</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Part I of the study is designed to define the Maximum Tolerated Dose/ Recommended Phase 2 Dose (MTD/RP2D) of CAN04 in subjects with relapsed or refractory Non-Small Cell Lung Cancer (NSCLC), Pancreatic Ductal Adenocarcinoma (PDAC), Triple Negative Breast Cancer (TNBC) or Colorectal Cancer (CRC). [Completed December 2018]&#xD;
Part II consists of six treatment arms and aims to establish the safety and tolerability of CAN04 as monotherapy and in combination with the standard of care in subjects with NSCLC or PDAC, as well as to investigate early signs of efficacy [Enrollment to monotherapy arms completed].</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)</measure>
    <time_frame>From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever occurs first</time_frame>
    <description>The incidence of Grade 3 or higher adverse events (AEs) related to CAN04 administration and according to the National Cancer Institute - Common Terminology Criteria for Adverse Events (CTCAE, version 4.03).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum concentration (Cmax)</measure>
    <time_frame>5 weeks</time_frame>
    <description>Maximum plasma concentration of CAN04</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal half-life (t1/2)</measure>
    <time_frame>5 weeks</time_frame>
    <description>Terminal half-life of CAN04</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clearance (CL)</measure>
    <time_frame>5 weeks</time_frame>
    <description>Plasma clearance of CAN04</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent volume of distribution during the terminal phase (VZ)</measure>
    <time_frame>5 weeks</time_frame>
    <description>Apparent volume of distribution of CAN04 during the terminal phase</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the curve from time 0 to infinity (AUC0-∞)</measure>
    <time_frame>5 weeks</time_frame>
    <description>Area under the plasma concentration curve from time 0 to infinity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anti-drug antibodies (ADA) against CAN04</measure>
    <time_frame>Through study completion, an average of 6 months</time_frame>
    <description>Immunogenicity of CAN04 after repeated administrations, assessed by ADA titers in serum.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Preliminary signs of efficacy as assessed by tumor response</measure>
    <time_frame>One year</time_frame>
    <description>Tumor response (irRC Part I Part II Monotherapy arms; iRECIST Part II Combination arms)</description>
  </secondary_outcome>
  <number_of_arms>7</number_of_arms>
  <enrollment type="Anticipated">140</enrollment>
  <condition>Non Small Cell Lung Cancer</condition>
  <condition>Pancreatic Ductal Adenocarcinoma</condition>
  <condition>Triple Negative Breast Cancer</condition>
  <condition>Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>Dose escalation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cohorts of 3 subjects will receive once weekly (Q1W) treatment with CAN04. The Dose Limiting Toxicity (DLT) observation period for each dose level will be the first 21 days of treatment with CAN04. [Completed December 2018]</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Monotherapy (Q1W)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects with either PDAC or NSCLC, will receive treatment with CAN04 monotherapy once weekly (Q1W).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Monotherapy (Q1W/Q2W)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects with either PDAC or NSCLC, will receive treatment with CAN04 monotherapy once weekly (Q1W) for the first 6 weeks followed by treatment every second week (Q2W).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Combination - NSCLC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects with NSCLC will receive treatment with CAN04 once weekly (Q1W) for the first 6 weeks followed by treatment every second week (Q2W) in combination with standard-of-care therapy (cisplatin/gemcitabine).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Combination - PDAC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects with PDAC will receive treatment with CAN04 once weekly (Q1W) for the first 6 weeks followed by treatment every second week (Q2W) in combination with standard-of-care therapy (nab-paclitaxel/gemcitabine).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Combination - PDAC (1 mg/kg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects with PDAC will receive CAN04 on Day 1 and 15 in cycles of 28 days in combination with standard-of-care therapy (nab-paclitaxel/gemcitabine). During first cycle CAN04 also to be administered on Day 8.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Combination - PDAC (2,5 mg/kg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects with PDAC will receive CAN04 on Day 1 and 15 in cycles of 28 days in combination with standard-of-care therapy (nab-paclitaxel/gemcitabine). During first cycle CAN04 also to be administered on Day 8.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CAN04</intervention_name>
    <description>A fully humanized monoclonal immunoglobulin G1 (IgG1) antibody (hmAb) in aqueous solution administered by i.v. infusion.</description>
    <arm_group_label>Combination - NSCLC</arm_group_label>
    <arm_group_label>Combination - PDAC</arm_group_label>
    <arm_group_label>Combination - PDAC (1 mg/kg)</arm_group_label>
    <arm_group_label>Combination - PDAC (2,5 mg/kg)</arm_group_label>
    <arm_group_label>Dose escalation</arm_group_label>
    <arm_group_label>Monotherapy (Q1W)</arm_group_label>
    <arm_group_label>Monotherapy (Q1W/Q2W)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>Standard of care treatment</description>
    <arm_group_label>Combination - NSCLC</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gemcitabine</intervention_name>
    <description>Standard of care treatment</description>
    <arm_group_label>Combination - NSCLC</arm_group_label>
    <arm_group_label>Combination - PDAC</arm_group_label>
    <arm_group_label>Combination - PDAC (1 mg/kg)</arm_group_label>
    <arm_group_label>Combination - PDAC (2,5 mg/kg)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nab-paclitaxel</intervention_name>
    <description>Standard of care treatment</description>
    <arm_group_label>Combination - PDAC</arm_group_label>
    <arm_group_label>Combination - PDAC (1 mg/kg)</arm_group_label>
    <arm_group_label>Combination - PDAC (2,5 mg/kg)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥ 18 year.&#xD;
&#xD;
          2. Measurable disease in accordance to iRECIST by computed tomography (CT) or magnetic&#xD;
             resonance imaging (MRI) scan, no more than 6 weeks prior to screening.&#xD;
&#xD;
          3. At least 4 weeks since the last dose of radiation therapy, immunotherapy, or surgery;&#xD;
             at least 6 weeks for therapy which is known to have delayed toxicity; at least 4 weeks&#xD;
             since treatment with biologic/targeted therapies.&#xD;
&#xD;
          4. Eastern Cooperative Oncology Group (ECOG) performance status ≤1.&#xD;
&#xD;
          5. Histologically or cytologically confirmed diagnosis of unresectable stage III or stage&#xD;
             IV squamous or non-squamous NSCLC (applicable Part II, Combination - NSCLC arm only).&#xD;
&#xD;
               -  Subjects must be eligible to receive first line standard chemotherapy regimen&#xD;
                  with cisplatin/gemcitabine or a second line standard chemotherapy regimen with&#xD;
                  cisplatin/gemcitabine after relapsing from first line with pembrolizumab&#xD;
                  monotherapy.&#xD;
&#xD;
               -  Subjects with actionable mutations (EGFR, ALK, ROS) can be enrolled if they have&#xD;
                  previously progressed to all approved standard of care targeted therapies and the&#xD;
                  next line of standard therapy is a platinum doublet.&#xD;
&#xD;
          6. Newly diagnosed, treatment naїve, histologically confirmed, unresectable, locally&#xD;
             advanced or metastatic (stage III or stage IV) PDAC (applicable Part II, Combination -&#xD;
             PDAC arm only).&#xD;
&#xD;
               -  Subjects must be eligible to receive treatment with nab-paclitaxel and&#xD;
                  gemcitabine.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects receiving live vaccination, etanercept or other TNF-α inhibitors or any other&#xD;
             investigational agents during or just prior to (within 28 days of first study drug&#xD;
             administration) participation in this study.&#xD;
&#xD;
          2. Clinical evidence of an active metastatic second malignancy.&#xD;
&#xD;
          3. Subjects with a life expectancy &lt;12 weeks.&#xD;
&#xD;
          4. Uncontrolled or significant cardiovascular disease defined as New York Heart&#xD;
             Association Classification III, or IV.&#xD;
&#xD;
          5. Immunocompromised subject currently receiving systemic therapy.&#xD;
&#xD;
          6. Other medical conditions that in the opinion of the investigator disqualify the&#xD;
             subject for inclusion.&#xD;
&#xD;
          7. Applicable Part II, Combination - NSCLC arm only&#xD;
&#xD;
               -  Prior lines of treatment with anti-cancer medication other than pembrolizumab&#xD;
                  administered as 1st line.&#xD;
&#xD;
               -  Known tumor EGFR mutation, unless contraindication to EGFR-directed therapy or if&#xD;
                  the subject has progressed to all approved anti-EGFR therapies.&#xD;
&#xD;
               -  Known tumor ALK rearrangements, unless contraindication to ALK-directed therapy&#xD;
                  or ALK-directed therapy not available or if the subject has progressed to all&#xD;
                  approved anti-EGFR therapies.&#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>Ahmad Awada, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Jules Bordet Institute, Brussels, Belgium</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ignacio Garcia-Ribas, MD, PhD</last_name>
    <phone>+46 46 2756260</phone>
    <email>clinicaltrials@cantargia.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Susanne Magnusson, PhD</last_name>
    <email>clinicaltrials@cantargia.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Landeskrankenhaus Salzburg</name>
      <address>
        <city>Salzburg</city>
        <zip>5020</zip>
        <country>Austria</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Medizinische Universität Wien</name>
      <address>
        <city>Vienna</city>
        <zip>A-1090</zip>
        <country>Austria</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Institut Jules Bordet</name>
      <address>
        <city>Brussels</city>
        <zip>1000</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christiane Jungels, Dr</last_name>
      <phone>+32 2 541 7342</phone>
      <email>christiane.jungels@bordet.be</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>University Hospital Gasthuisberg</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Eric Van Cutsem, Prof. Dr.</last_name>
      <phone>+32 16 34 42 18</phone>
      <email>eric.vancutsem@uzleuven.be</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>CHU de Liège</name>
      <address>
        <city>Liège</city>
        <zip>B-4000</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joelle Collignon, MD</last_name>
      <phone>32 4 366 82 50</phone>
      <email>joelle.collignon@chuliege.be</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Aalborg University Hospital</name>
      <address>
        <city>Aalborg</city>
        <zip>9000</zip>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Laurids Oestergaard Poulsen, MD, PhD</last_name>
      <phone>+45 616 520 01</phone>
      <email>laop@rn.dk</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Rigshospitalet, Department of Oncology</name>
      <address>
        <city>Copenhagen</city>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ulrik Lassen, Prof, MD,PhD</last_name>
      <phone>+45 354 58 923</phone>
      <email>Ulrik.Lassen@regionh.dk</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Herlev og Gentofte Hospital</name>
      <address>
        <city>Herlev</city>
        <zip>2730</zip>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rikke Eefsen, MD, PhD</last_name>
      <phone>+45 38 68 9381</phone>
      <email>rikke.helene.loevendahl.eefsen@regionh.dk</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Odense University Hospital</name>
      <address>
        <city>Odense</city>
        <zip>5000</zip>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Per Pfeiffer, Prof. Dr.</last_name>
      <phone>+45 65 41 15 90</phone>
      <email>per.pfeiffer@rsyd.dk</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>East Tallinn Central Hospital</name>
      <address>
        <city>Tallinn</city>
        <zip>11312</zip>
        <country>Estonia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gerli Kuusk, MD</last_name>
      <phone>+37 26 661 900</phone>
      <email>gerli.kuusk@itk.ee</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Tartu University Hospital</name>
      <address>
        <city>Tartu</city>
        <zip>50406</zip>
        <country>Estonia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Andrus Mägi, MD</last_name>
    </contact>
    <contact_backup>
      <email>Andrus.Magi@kliinikum.ee</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Charité Universitätsmedizin Berlin</name>
      <address>
        <city>Berlin</city>
        <zip>10117</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sebastian Ochsenreither, PD Dr. med.</last_name>
      <phone>+49 30 450 564 960</phone>
      <email>sebastian.ochsenreither@charite.de</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikums Frankfurt am Main</name>
      <address>
        <city>Frankfurt</city>
        <zip>60590</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Asklepios Klinik Altona</name>
      <address>
        <city>Hamburg</city>
        <zip>227 63</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dirk Arnold, Prof. Dr. med.</last_name>
      <phone>+49 40 1818 81 1210</phone>
      <email>d.arnold@asklepios.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Ulm</name>
      <address>
        <city>Ulm</city>
        <zip>89081</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Thomas Seufferlein, Prof. Dr. med.</last_name>
      <phone>+49 731 500 56098</phone>
      <email>thomas.seufferlein@uniklinik-ulm.de</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Pauls Stradiņš Clinical University Hospital</name>
      <address>
        <city>Riga</city>
        <zip>1002</zip>
        <country>Latvia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gunta Purkalne, Prof. Dr. med.</last_name>
      <phone>+37 129 410 710</phone>
      <email>gunta.purkalne@stradini.lv</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Riga East Clinical University Hospital</name>
      <address>
        <city>Riga</city>
        <zip>1079</zip>
        <country>Latvia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Zanete Zvirbule, MD</last_name>
      <phone>+37 129 536 734</phone>
      <email>zanete.zvirbule@aslimnica.lv</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>The Hospital of Lithuanian University of Health Sciences</name>
      <address>
        <city>Kaunas</city>
        <zip>50161</zip>
        <country>Lithuania</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marius Zemaitis, MD, PhD</last_name>
      <phone>+37 032 65 54</phone>
      <email>marius.zemaitis@kaunoklinikos.lt</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>The Hospital of Lithuanian University of Health Sciences</name>
      <address>
        <city>Kaunas</city>
        <zip>50161</zip>
        <country>Lithuania</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Audrius Ivanauskas, MD</last_name>
      <email>audrius.ivanauskas@kaunoklinikos.lt</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>National Cancer Institute</name>
      <address>
        <city>Vilnius</city>
        <zip>08660</zip>
        <country>Lithuania</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Saulius Cicenas, Prof. MD</last_name>
      <phone>+37 052 19 09 18</phone>
      <email>klinikiniaityrimai@nvi.lt</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>National Cancer Institute</name>
      <address>
        <city>Vilnius</city>
        <zip>08660</zip>
        <country>Lithuania</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Edita Baltruskeviciene, MD</last_name>
      <email>edita.baltruskeviciene@nvi.lt</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Netherlands Cancer Institute</name>
      <address>
        <city>Amsterdam</city>
        <zip>1066 CX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Erasmus University Medical Center, Department of Medical Oncology</name>
      <address>
        <city>Rotterdam</city>
        <zip>3015 CE</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Oslo University Hospital, Radiumhospitalet</name>
      <address>
        <city>Oslo</city>
        <zip>0379</zip>
        <country>Norway</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Hospital 12 de Octubre</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Luis Gonzaga Paz-Ares Rodriguez, MD</last_name>
      <phone>+34 91 390 8000</phone>
      <email>lpazaresr@seom.org</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Quirónsalud Madrid</name>
      <address>
        <city>Madrid</city>
        <zip>28223</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Belén Rubio Viqueira, MD</last_name>
      <phone>+34 914 52 19 87</phone>
      <email>belen.rubio@quironsalud.es</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Central de Asturias</name>
      <address>
        <city>Oviedo</city>
        <zip>33011</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Emilio Esteban González, MD</last_name>
      <phone>+34 985 10 61 21</phone>
      <email>eestebang@seom.org</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Karolinska University Hospital</name>
      <address>
        <city>Stockholm</city>
        <zip>171 64</zip>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jeffrey Yachnin, MD, PhD</last_name>
      <phone>+46 85 177 3193</phone>
      <email>jeffrey.yachnin@sll.se</email>
    </contact>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>Belgium</country>
    <country>Denmark</country>
    <country>Estonia</country>
    <country>Germany</country>
    <country>Latvia</country>
    <country>Lithuania</country>
    <country>Netherlands</country>
    <country>Norway</country>
    <country>Spain</country>
    <country>Sweden</country>
  </location_countries>
  <link>
    <url>https://cantargia.com/assets/uploads/Poster-CANFOUR-ESMO-2018-version-FINAL.pdf</url>
    <description>Poster presentation at ESMO 2018</description>
  </link>
  <link>
    <url>https://cantargia.com/assets/uploads/ASCO2019_CANFOUR-Phase-I_FINAL-01June_2019.pdf</url>
    <description>Oral presentation at ASCO 2019</description>
  </link>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>August 24, 2017</study_first_submitted>
  <study_first_submitted_qc>August 29, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 30, 2017</study_first_posted>
  <last_update_submitted>August 4, 2021</last_update_submitted>
  <last_update_submitted_qc>August 4, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 11, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>First-in-Human</keyword>
  <keyword>Phase 1</keyword>
  <keyword>Phase 2</keyword>
  <keyword>Antibody, Monoclonal</keyword>
  <keyword>IL1RAP</keyword>
  <keyword>Safety</keyword>
  <keyword>Tolerability</keyword>
  <keyword>Cancer</keyword>
  <keyword>Solid tumor</keyword>
  <keyword>Malignant</keyword>
  <keyword>Dose escalation</keyword>
  <keyword>Dose expansion</keyword>
  <keyword>CAN04</keyword>
  <keyword>Immunoglobulin</keyword>
  <keyword>Clinical Trial</keyword>
  <keyword>Infusion</keyword>
  <keyword>Antineoplastic</keyword>
  <keyword>Anticancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Triple Negative Breast Neoplasms</mesh_term>
    <mesh_term>Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Gemcitabine</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03267316
org study id: CAN04CLIN001
secondary id: 2017-001111-36
nct id: NCT03267316
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study will evaluate the safety, tolerability, and preliminary antitumor activity of
      CAN04 both as a monotherapy and in combination with standard of care treatment in subjects
      with solid cancer tumors.

      Following completion of the first part, the dose escalation cohorts, and determination of
      maximum tolerated dose or recommended phase 2 dose (MTD/RP2D), safety and tolerability will
      be further evaluated in an expanded cohort of subjects with pancreatic or lung cancer, as
      monotherapy or in combination with the standard of care treatment, to identify the RP2D of
      CAN04 in combination with standard of care. In addition, early signs of efficacy during
      treatment with CAN04 will be investigated.
CAN04 is a first-in-class fully humanized and ADCC enhanced monoclonal antibody, targeting
      the Interleukin 1 Receptor Accessory Protein (IL1RAP).

      The CAN04 strategy is to attack the IL1RAP target molecule using an effective antibody-based
      cancer treatment. In preclinical (in vitro and in vivo) studies, CAN04 has shown two distinct
      mechanisms of action:

        1. By blocking the intracellular signals from the IL1RAP target molecule, thereby impairing
           the cancer cells' ability to secrete tumor stimulating cytokines, in turn reducing tumor
           inflammation and tumor progression.

        2. Through antibody dependent cellular cytotoxicity (ADCC) against IL1RAP expressing tumor
           cells where CAN04 stimulates natural killer (NK) cells to attack the tumor cells.

      The study is a combined phase 1/2a, open-label, dose-escalation followed by dose expansion,
      safety and tolerability clinical trial, in patients with relapsed or refractory solid tumors.
      It consists of two parts.

      In Part I (Dose Escalation - DE), the intention is to include patients with any of the four
      solid tumor types: Non-Small Cell Lung Cancer (NSCLC), Pancreatic Ductal Adenocarcinoma
      (PDAC), Triple Negative Breast Cancer (TNBC) or Colorectal Cancer (CRC). In this part of the
      study safety and tolerability will be documented and the MTD/ RP2D will be determined.
      Patients will stay on CAN04 treatment until disease progression, unacceptable toxicity, or
      discontinuation for any other reason. [Completed December 2018]

      In Part II (Expansion Cohort - EC), safety and tolerability will be further evaluated in an
      expanded cohort of subjects with PDAC or NSCLC at the RP2D level. In addition, early signs of
      efficacy during treatment with CAN04 will be investigated, as monotherapy or in combination
      with the standard of care.

      Patients will stay on treatment until disease progression, unacceptable toxicity, or
      discontinuation for any other reason. [Enrollment to monotherapy arms completed]
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: Part I of the study is designed to define the Maximum Tolerated Dose/ Recommended Phase 2 Dose (MTD/RP2D) of CAN04 in subjects with relapsed or refractory Non-Small Cell Lung Cancer (NSCLC), Pancreatic Ductal Adenocarcinoma (PDAC), Triple Negative Breast Cancer (TNBC) or Colorectal Cancer (CRC). [Completed December 2018]
Part II consists of six treatment arms and aims to establish the safety and tolerability of CAN04 as monotherapy and in combination with the standard of care in subjects with NSCLC or PDAC, as well as to investigate early signs of efficacy [Enrollment to monotherapy arms completed].
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
time frame: From the first dose until the last subject has completed their end of trial visit or the last enrolled subject has completed 6 months of treatment, whichever occurs first
description: The incidence of Grade 3 or higher adverse events (AEs) related to CAN04 administration and according to the National Cancer Institute - Common Terminology Criteria for Adverse Events (CTCAE, version 4.03).
measure: Maximum concentration (Cmax)
time frame: 5 weeks
description: Maximum plasma concentration of CAN04
measure: Terminal half-life (t1/2)
time frame: 5 weeks
description: Terminal half-life of CAN04
measure: Clearance (CL)
time frame: 5 weeks
description: Plasma clearance of CAN04
measure: Apparent volume of distribution during the terminal phase (VZ)
time frame: 5 weeks
description: Apparent volume of distribution of CAN04 during the terminal phase
measure: Area under the curve from time 0 to infinity (AUC0-∞)
time frame: 5 weeks
description: Area under the plasma concentration curve from time 0 to infinity
measure: Anti-drug antibodies (ADA) against CAN04
time frame: Through study completion, an average of 6 months
description: Immunogenicity of CAN04 after repeated administrations, assessed by ADA titers in serum.
measure: Preliminary signs of efficacy as assessed by tumor response
time frame: One year
description: Tumor response (irRC Part I Part II Monotherapy arms; iRECIST Part II Combination arms)
arm group label: Dose escalation
arm group type: Experimental
description: Cohorts of 3 subjects will receive once weekly (Q1W) treatment with CAN04. The Dose Limiting Toxicity (DLT) observation period for each dose level will be the first 21 days of treatment with CAN04. [Completed December 2018]
arm group label: Monotherapy (Q1W)
arm group type: Experimental
description: Subjects with either PDAC or NSCLC, will receive treatment with CAN04 monotherapy once weekly (Q1W).
arm group label: Monotherapy (Q1W/Q2W)
arm group type: Experimental
description: Subjects with either PDAC or NSCLC, will receive treatment with CAN04 monotherapy once weekly (Q1W) for the first 6 weeks followed by treatment every second week (Q2W).
arm group label: Combination - NSCLC
arm group type: Experimental
description: Subjects with NSCLC will receive treatment with CAN04 once weekly (Q1W) for the first 6 weeks followed by treatment every second week (Q2W) in combination with standard-of-care therapy (cisplatin/gemcitabine).
arm group label: Combination - PDAC
arm group type: Experimental
description: Subjects with PDAC will receive treatment with CAN04 once weekly (Q1W) for the first 6 weeks followed by treatment every second week (Q2W) in combination with standard-of-care therapy (nab-paclitaxel/gemcitabine).
arm group label: Combination - PDAC (1 mg/kg)
arm group type: Experimental
description: Subjects with PDAC will receive CAN04 on Day 1 and 15 in cycles of 28 days in combination with standard-of-care therapy (nab-paclitaxel/gemcitabine). During first cycle CAN04 also to be administered on Day 8.
arm group label: Combination - PDAC (2,5 mg/kg)
arm group type: Experimental
description: Subjects with PDAC will receive CAN04 on Day 1 and 15 in cycles of 28 days in combination with standard-of-care therapy (nab-paclitaxel/gemcitabine). During first cycle CAN04 also to be administered on Day 8.
intervention type: Biological
intervention name: CAN04
description: A fully humanized monoclonal immunoglobulin G1 (IgG1) antibody (hmAb) in aqueous solution administered by i.v. infusion.
arm group label: Combination - NSCLC
arm group label: Combination - PDAC
arm group label: Combination - PDAC (1 mg/kg)
arm group label: Combination - PDAC (2,5 mg/kg)
arm group label: Dose escalation
arm group label: Monotherapy (Q1W)
arm group label: Monotherapy (Q1W/Q2W)
intervention type: Drug
intervention name: Cisplatin
description: Standard of care treatment
arm group label: Combination - NSCLC
intervention type: Drug
intervention name: Gemcitabine
description: Standard of care treatment
arm group label: Combination - NSCLC
arm group label: Combination - PDAC
arm group label: Combination - PDAC (1 mg/kg)
arm group label: Combination - PDAC (2,5 mg/kg)
intervention type: Drug
intervention name: Nab-paclitaxel
description: Standard of care treatment
arm group label: Combination - PDAC
arm group label: Combination - PDAC (1 mg/kg)
arm group label: Combination - PDAC (2,5 mg/kg)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ahmad Awada, Professor
role: Principal Investigator
affiliation: Jules Bordet Institute, Brussels, Belgium
last name: Ignacio Garcia-Ribas, MD, PhD
phone: +46 46 2756260
email: clinicaltrials@cantargia.com
last name: Susanne Magnusson, PhD
email: clinicaltrials@cantargia.com
facility: 
status: Completed
facility: 
status: Completed
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
facility: 
status: Withdrawn
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Completed
facility: 
status: Completed
facility: 
status: Completed
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: Austria
country: Belgium
country: Denmark
country: Estonia
country: Germany
country: Latvia
country: Lithuania
country: Netherlands
country: Norway
country: Spain
country: Sweden
url: https://cantargia.com/assets/uploads/Poster-CANFOUR-ESMO-2018-version-FINAL.pdf
description: Poster presentation at ESMO 2018
url: https://cantargia.com/assets/uploads/ASCO2019_CANFOUR-Phase-I_FINAL-01June_2019.pdf
description: Oral presentation at ASCO 2019
responsible party type: Sponsor
mesh term: Triple Negative Breast Neoplasms
mesh term: Neoplasms
mesh term: Paclitaxel
mesh term: Gemcitabine