<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/NCT03252938</url>
  </required_header>
  <id_info>
    <org_study_id>INSIGHT</org_study_id>
    <nct_id>NCT03252938</nct_id>
  </id_info>
  <brief_title>Feasibility and Safety of IMP321 (Eftilagimod Alpha) for Advanced Stage Solid Tumors</brief_title>
  <official_title>An Explorative, Open-labeled, Phase I Study to Evaluate the Feasibility and the Safety of IMP321 in Combination With Immunotherapeutic/Targeted/Chemotherapeutic Agents or Via New Routes of Application in Advanced Stage Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest</source>
  <oversight_info>
    <has_dmc>Yes</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 phase I trial aims to investigate a potential enhancement of IMP321 immune-activating&#xD;
      effects by new routes of administration: direct injection of IMP321 into the tumor tissue;&#xD;
      intra-peritoneal therapy; combination of chemotherapy and/or immunotherapy/targeted therapy&#xD;
      with active immunotherapy&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Up to now, IMP321 is solely administered by sub-cutaneous injection (e.g. on the anterior&#xD;
      face of the thigh). In this study, we investigate whether a direct injection of IMP321 into&#xD;
      the tumor tissue will be a useful option to improve anti-tumor immune response by placing the&#xD;
      immune-therapeutic agent in direct vicinity of immune infiltrates in the tumor bed. This&#xD;
      bypasses processes necessary for drug delivery to cells of solid tumors following systemic&#xD;
      administration, like transport within vessels, transport across vasculature walls into&#xD;
      surrounding tissues, and - in cases of peritoneal metastases - transport through the&#xD;
      interstitial space within a tumor. For the latter case, we will also explore if an&#xD;
      intra-peritoneal therapy represents a feasible alternative by means of delivering high drug&#xD;
      concentrations directly to tumors located in the peritoneal cavity.&#xD;
&#xD;
      Furthermore, we will explore the possibility to extend the positive results obtained by&#xD;
      subcutaneous injections of IMP321 in metastatic renal cell and breast carcinomas to further&#xD;
      solid tumor entities. In this part of the study, patients will be treated with the&#xD;
      standard-of-care (SOC) chemotherapy and/or immunotherapy/targeted therapy for their tumor&#xD;
      entity along with subcutaneous injections of IMP321.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 15, 2017</start_date>
  <completion_date type="Anticipated">September 30, 2025</completion_date>
  <primary_completion_date type="Anticipated">September 30, 2025</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Feasibility rate</measure>
    <time_frame>10 weeks of treatment + 2 weeks of safety observation period</time_frame>
    <description>Rate of patients receiving the protocol treatment without occurrence of a dose limiting toxicity</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence and severity of adverse events according to CTC criteria</measure>
    <time_frame>12 months of treatment + 12 months of Follow Up</time_frame>
    <description>Incidence and severity of adverse events according to the current National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response</measure>
    <time_frame>12 months of Follow Up</time_frame>
    <description>Objective response rate according to RECIST 1.1 and endoscopic response criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>12 months of Follow Up</time_frame>
    <description>PFS will be measured as time from inclusion until disease progression or death of any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>12 months of Follow Up</time_frame>
    <description>OS will be measured as time from inclusion to death of any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immune response in whole blood and tumor tissue</measure>
    <time_frame>12 months of treatment + 12 months of Follow Up</time_frame>
    <description>Peripheral blood monocyte number and CD8 T-cell number, associated activation markers, tumor-infiltrating immune cells</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Anticipated">110</enrollment>
  <condition>Solid Tumors</condition>
  <condition>Peritoneal Carcinomatosis</condition>
  <arm_group>
    <arm_group_label>Solid tumors</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Biweekly intra-tumoral injections of escalating doses (6 mg, 12 mg, 24 mg and 30 mg) of IMP321 as a monotherapy (intratumoral injections in parenchymatous organs (e.g. liver, spleen, adrenal gland, pancreas) are not allowed)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Solid tumors + peritoneal carcinomatosis</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Biweekly intra-peritoneal, escalating doses of IMP321 (1 mg, 3 mg, 6 mg, 12 mg and 30 mg)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Solid tumors + chemotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subcutaneous (s.c.) injections with the optimal dose of IMP321 defined in the AIPAC trial for a maximum of 24 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Solid tumors + Avelumab/IMP321 therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Avelumab and IMP321 as follows:&#xD;
800 mg avelumab every 2 weeks i.v. (for a maximum of 24 cycles [48 weeks])&#xD;
6 mg (cohort 1) or 30 mg (cohort 2) IMP321 every 2 weeks s.c. (for a maximum of 12 cycles [24 weeks])</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Solid tumors + Avelumab/IMP321 combination therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Avelumab and IMP321 as follows:&#xD;
• 800 mg avelumab every 2 weeks i.v. and 30 mg IMP321 every 2 weeks s.c. for a maximum of 24 cycles [12 months]</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IMP321</intervention_name>
    <description>LAG-3Ig fusion protein, highly potent activator of antigen presenting cells</description>
    <arm_group_label>Solid tumors</arm_group_label>
    <arm_group_label>Solid tumors + Avelumab/IMP321 combination therapy</arm_group_label>
    <arm_group_label>Solid tumors + Avelumab/IMP321 therapy</arm_group_label>
    <arm_group_label>Solid tumors + chemotherapy</arm_group_label>
    <arm_group_label>Solid tumors + peritoneal carcinomatosis</arm_group_label>
    <other_name>LAG-3Ig fusion protein</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Avelumab</intervention_name>
    <description>Avelumab i.v.</description>
    <arm_group_label>Solid tumors + Avelumab/IMP321 combination therapy</arm_group_label>
    <arm_group_label>Solid tumors + Avelumab/IMP321 therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically confirmed locally advanced (not manageable with curative intent) or&#xD;
             metastatic solid tumor Specification for Stratum C: Only patients with NSCLC&#xD;
             adenocarcinomas, (squamous or adenosquamous not permitted) who are scheduled to&#xD;
             receive platin + pembrolizumab + pemetrexed standard treatment (only for Stratum C)&#xD;
             Specification for Stratum E: Including only metastatic or irresectable locally&#xD;
             advanced urothelial carcinomas - also refer to IC#15 below (only for Stratum E)&#xD;
&#xD;
          2. Tumor is accessible for repeated injections and biopsies (only for Stratum A)&#xD;
&#xD;
          3. Peritoneal carcinomatosis (only for Stratum B)&#xD;
&#xD;
          4. Patient failed standard therapy or refused standard therapy or is intolerable towards&#xD;
             standard therapy (Strata A, B, and D) or who receives Standard-of-Care first line&#xD;
             treatment comprising platin + pembrolizumab + pemetrexed (only for Stratum C)&#xD;
&#xD;
          5. Patient has not received more than 4 prior lines of therapy. Neoadjuvant/adjuvant&#xD;
             treatment is not counted unless progression occurs &lt;6 months after completion of the&#xD;
             treatment. In these cases, neoadjuvant/adjuvant treatment is counted as one prior line&#xD;
             (only for Stratum D).&#xD;
&#xD;
             Specification for Stratum C: Only patients receiving first line Standard-of-Care&#xD;
             therapy (platin + pembrolizumab + pemetrexed; only for Stratum C) Specification for&#xD;
             Stratum E: Refer to IC#15 below with regards to previous lines of therapy; only for&#xD;
             Stratum E) Note exclusion criterion #7 on exclusion of defined previous cancer&#xD;
             immunotherapy (only for Strata D and E)&#xD;
&#xD;
          6. Patients ≥ 18 years. Patients in reproductive age must be willing to use highly&#xD;
             effective contraception during the study and 4 months after the end of the study&#xD;
             (appropriate contraception is defined as combined (estrogen and progestogen&#xD;
             containing) hormonal contraception associated with inhibition of ovulation,&#xD;
             progestogen-only hormonal contraception associated with inhibition of ovulation,&#xD;
             intrauterine device (IUD), intrauterine hormone-releasing system (IUS), vasectomized&#xD;
             partner, bilateral tubal occlusion, sexual abstinence. If an oral contraception is&#xD;
             used, a barrier method of contraception (e.g. male condom, female condom, cervical&#xD;
             cap, diaphragm, contraceptive sponge) has to be applied additionally.). Female&#xD;
             patients with childbearing potential need to have a negative pregnancy test within 7&#xD;
             days before study start.&#xD;
&#xD;
          7. ECOG 0 or 1&#xD;
&#xD;
          8. Adequate hematological, hepatic and renal function parameters:&#xD;
&#xD;
               -  ANC (absolute neutrophil count) ≥ 1.500/µl&#xD;
&#xD;
               -  Leukocytes ≥ 3.000/µl&#xD;
&#xD;
               -  Platelets ≥ 75.000/µl (for Stratum D: ≥ 100.000/µl)&#xD;
&#xD;
               -  Serum creatinine ≤ 1.5 x upper limit of normal, or GFR ≥ 50 ml/min&#xD;
&#xD;
               -  Bilirubin ≤ 1.5 - 3 x upper limit of normal (for Stratum D: ≤ 1.5 x ULN)&#xD;
&#xD;
               -  AST and ALT ≤ 3 x upper limit of normal (≤ 5 x if liver metastases are present)&#xD;
                  (for Stratum D: AST and ALT ≤ 2.5 x ULN; ≤ 5 x if liver metastases are present)&#xD;
&#xD;
               -  Alkaline phosphatase ≤ 6 x upper limit of normal&#xD;
&#xD;
               -  Hemoglobin ≥ 9g/dL&#xD;
&#xD;
          9. Adequate coagulation functions as defined by International Normalized Ratio (INR) ≤&#xD;
             1.5, and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN (unless&#xD;
             receiving anticoagulation therapy). Patients receiving warfarin/ phenprocoumon must be&#xD;
             switched to low molecular weight heparin and have achieved stable coagulation profile.&#xD;
&#xD;
         10. Patient able and willing to provide written informed consent and to comply with the&#xD;
             study protocol and with the planned surgical procedures&#xD;
&#xD;
         11. Evidence of measurable disease as defined by RECIST v1.1 (only for Strata C, D and E)&#xD;
             or assessable disease as defined by RECIST v1.1 (only for Stratum C)&#xD;
&#xD;
         12. Expected survival &gt; 3 months&#xD;
&#xD;
         13. Resolution of toxicity associated with prior or current therapy to grade &lt;2 (except&#xD;
             for alopecia and transaminases in case of liver metastases)&#xD;
&#xD;
         14. Patient is eligible if one of the following settings applies (only for Stratum E):&#xD;
&#xD;
               -  did not receive any prior systemic therapy for metastatic disease AND would be&#xD;
                  eligible for platinum-based therapy AND has a PD-L1 CPS ≥10 or&#xD;
&#xD;
               -  did not receive any prior systemic therapy for metastatic disease AND is not&#xD;
                  eligible for platinum-based therapy, independent from PD-L1 CPS status or&#xD;
&#xD;
               -  did suffer disease progression during/directly after a platinum-based&#xD;
                  chemotherapy for metastatic disease AND did not receive avelumab maintenance&#xD;
                  therapy after platinum-based chemotherapy, independent from PD-L1 CPS status&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Inability to understand the aims of the study and/or protocol procedures&#xD;
&#xD;
          2. Bleeding ulcerative tumors or tumors requiring intratumoral injections of study drug&#xD;
             into parenchymatous organs such as, but limited to liver, spleen or pancreas (only for&#xD;
             Stratum A)&#xD;
&#xD;
          3. Patients with contraindication versus a laparoscopy or refusing a laparoscopy (only&#xD;
             for Stratum B)&#xD;
&#xD;
          4. Hypersensitivity towards eftilagimod alpha, avelumab (only for Strata D and E), or any&#xD;
             ingredient of the injection/infusion solutions&#xD;
&#xD;
          5. History of severe allergic, anaphylactic, or other hypersensitivity reactions to&#xD;
             chimeric or humanized antibodies or fusion proteins&#xD;
&#xD;
          6. Currently receiving any other antineoplastic treatment including irradiation, or&#xD;
             targeted small molecule therapy, or biological cancer therapy, or less than 4 weeks&#xD;
             since completion of these therapies and first dose of study treatment (only Strata A,&#xD;
             B, D and E)&#xD;
&#xD;
          7. Prior PD-1/PDL-1 targeted therapy (only for Strata D and E). NOTE: For Stratum E only,&#xD;
             patients can be enrolled if they received prior PD-1/PD-L1 targeted therapy during&#xD;
             neoadjuvant treatment. HOWEVER, only after at least a free interval of at least 12&#xD;
             months after neoadjuvant PD-1/PD-L1 addressed- therapy.&#xD;
&#xD;
          8. Cirrhosis of the liver (Child &gt; Grade A), pronounced alcohol abuse with anticipated&#xD;
             detoxification, severe pulmonary infection with considerable reduction of pulmonary&#xD;
             function&#xD;
&#xD;
          9. Clinically significant active coronary heart disease, cardiomyopathy or congestive&#xD;
             heart failure, NYHA III-IV (for Stratum D: ≥ NYHA II) within 6 months prior to first&#xD;
             dose of study treatment including: myocardial infarction, severe/unstable angina,&#xD;
             ongoing cardiac dysrhythmias of current NCI CTCAE version Grade &gt;2, atrial&#xD;
             fibrillation of any grade, coronary/peripheral artery bypass graft, symptomatic&#xD;
             congestive heart failure, cerebrovascular accident including transient ischemic&#xD;
             attack, ventricular arrhythmias requiring medication or symptomatic pulmonary embolism&#xD;
&#xD;
         10. Cerebral or leptomeningeal metastases Note: Subjects with previously treated brain&#xD;
             metastases may participate if they meet the following criteria: 1) are stable for at&#xD;
             least 28 days prior to the first dose of study treatment and if all neurologic&#xD;
             symptoms returned to baseline; 2) have no evidence of new or enlarging brain&#xD;
             metastases; and 3) have not been using steroids for at least 7 days prior to first&#xD;
             dose of study treatment. This exception does not include carcinomatous meningitis&#xD;
             which is excluded regardless of clinical stability.&#xD;
&#xD;
         11. Chronic inflammatory bowel disease&#xD;
&#xD;
         12. Active infection requiring systemic therapy at the start of study treatment or chronic&#xD;
             infection or serious intercurrent infection within 4 weeks prior to first dose of&#xD;
             study treatment&#xD;
&#xD;
         13. QTcF &gt;480 ms, family or personal history of long or short QT syndrome, Brugada&#xD;
             syndrome or known history of QTc prolongation, or Torsade de Pointes (TdP)&#xD;
&#xD;
         14. Uncontrolled electrolyte disorders that can worsen the effects of a QTc-prolonging&#xD;
             drug (e.g., hypocalcaemia, hypokalaemia, hypomagnesemia)&#xD;
&#xD;
         15. Positive test for human immunodeficiency virus (HIV) or known acquired&#xD;
             immunodeficiency syndrome. Testing is not required in the absence of history.&#xD;
&#xD;
             Participants with known human immunodeficiency virus (HIV) infections are eligible if&#xD;
             the following criteria are met:&#xD;
&#xD;
               1. If clinically indicated participants must be stable on antiretroviral therapy&#xD;
                  (ART) for at least 4 weeks and agree to adhere to ART. If not clinically&#xD;
                  indicated, consult Principal Investigator (LKP).&#xD;
&#xD;
               2. Participants with HIV infection should have no evidence of documented multidrug&#xD;
                  resistance that would prevent effective ART.&#xD;
&#xD;
               3. Have an HIV viral load of &lt; 400 copies/mL at Screening.&#xD;
&#xD;
               4. If prophylactic antimicrobial drugs are indicated, patient may still be&#xD;
                  considered eligible upon agreement with the Principal Investigator (LKP)&#xD;
&#xD;
         16. Active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg]&#xD;
             test) or hepatitis C Note: Patients with past hepatitis B virus (HBV) infection or&#xD;
             resolved HBV infection (defined as having a negative HBsAg test and a positive&#xD;
             antibody to hepatitis B core antigen antibody test) are eligible. Note: Patients&#xD;
             positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain&#xD;
             reaction testing is negative for HCV ribonucleic acid (RNA). Testing is not required&#xD;
             in the absence of history.&#xD;
&#xD;
         17. History or evidence of interstitial lung disease, active non-infectious pneumonitis or&#xD;
             active tuberculosis&#xD;
&#xD;
         18. Active or prior autoimmune disease requiring immunosuppressive therapy that might&#xD;
             deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I,&#xD;
             vitiligo, psoriasis, or hypo- or hyperthyroid disease not requiring immunosuppressive&#xD;
             treatment are eligible.&#xD;
&#xD;
         19. Known history of immune-mediated colitis, pneumonitis, pulmonary fibrosis (only for&#xD;
             Strata D and E).&#xD;
&#xD;
         20. Administration of a live, attenuated vaccine (including Covid-19 vaccination with&#xD;
             live, attenuated vaccine) within four weeks prior to start of treatment or&#xD;
             anticipation that such a live attenuated vaccine will be required during the remainder&#xD;
             of the study.&#xD;
&#xD;
         21. Any condition requiring continuous systemic treatment with either corticosteroids (&gt;10&#xD;
             mg daily prednisone equivalents) or other immunosuppressive medications within 4 weeks&#xD;
             prior to first dose of study treatment. Intranasal, inhaled or topical steroids, eye&#xD;
             drops or local steroid injection (eg, intra-articular injection), steroids as&#xD;
             premedication for hypersensitivity reactions (eg, computed tomography [CT] scan&#xD;
             premedication) and physiological replacement doses of up to 10 mg daily prednisone&#xD;
             equivalent are permitted in the absence of active autoimmune disease.&#xD;
&#xD;
         22. Treatment with systemic immunostimulatory agents (including but not limited to&#xD;
             interferons or interleukin-2) within four weeks or five half-lives of the drug,&#xD;
             whichever is shorter, prior to start of study treatment&#xD;
&#xD;
         23. Any previous venous thromboembolism &gt; National Cancer Institute (NCI) Common&#xD;
             Terminology Criteria for Adverse Events (CTCAE) Grade 3 within the last 6 months&#xD;
&#xD;
         24. Past history of severe allergic episodes and/ or Quincke's oedema&#xD;
&#xD;
         25. Prior organ transplantation or stem cell transplantation&#xD;
&#xD;
         26. On-treatment participation in another clinical study in the period 30 days prior to&#xD;
             start of study treatment and during the study&#xD;
&#xD;
         27. Patients in a closed institution according to an authority or court decision (AMG §&#xD;
             40, Abs. 1 No. 4)&#xD;
&#xD;
         28. Pregnancy or lactation&#xD;
&#xD;
         29. Planned intratumoral injections in parenchymatous organs (e.g. liver, spleen, adrenal&#xD;
             gland, pancreas)&#xD;
&#xD;
         30. Life-threatening illness unrelated to cancer&#xD;
&#xD;
         31. History of irAEs of CTCAE Grade 4 requiring steroid treatment (only for Strata C, D&#xD;
             and E)&#xD;
&#xD;
         32. Persisting toxicity related to prior therapy (NCI CTCAE current version Grade &gt; 1);&#xD;
             however, alopecia, sensory neuropathy Grade ≤2, or other Grade ≤2 AEs not constituting&#xD;
             a safety risk based on investigator's judgment are acceptable (only for Strata D and&#xD;
             E)&#xD;
&#xD;
         33. Other severe acute or chronic medical conditions, psychiatric conditions including&#xD;
             recent (within the past year) or active suicidal ideation or behavior; or laboratory&#xD;
             abnormalities that may increase the risk associated with study participation or study&#xD;
             treatment administration or may interfere with the interpretation of study results&#xD;
             and, in the judgment of the investigator, would make the patient inappropriate for&#xD;
             entry into this study.&#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>Thorsten Götze, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institute of Clinical Cancer Research (IKF), UCT Frankfurt, Germany</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Salah-Eddin Al-Batran, MD</last_name>
    <phone>+49 69 7601</phone>
    <phone_ext>4420</phone_ext>
    <email>albatran@ikf-khnw.de</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Sabine Beck, PhD</last_name>
    <phone>+49 69 7601</phone>
    <phone_ext>3955</phone_ext>
    <email>beck.sabine@ikf-khnw.de</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Krankenhaus Nordwest</name>
      <address>
        <city>Frankfurt</city>
        <zip>60488</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Thorsten O. Götze, Prof. Dr.</last_name>
      <phone>+4969 7601</phone>
      <phone_ext>4420</phone_ext>
      <email>Goetze.Thorsten@KHNW.DE</email>
    </contact>
    <contact_backup>
      <last_name>Sabine Beck, PhD</last_name>
      <phone>+4969 7601</phone>
      <phone_ext>3955</phone_ext>
      <email>beck.sabine@ikf-khnw.de</email>
    </contact_backup>
    <investigator>
      <last_name>Thorsten O. Götze, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>August 14, 2017</study_first_submitted>
  <study_first_submitted_qc>August 14, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 17, 2017</study_first_posted>
  <last_update_submitted>August 3, 2023</last_update_submitted>
  <last_update_submitted_qc>August 3, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>solid tumor</keyword>
  <keyword>peritoneal carcinomatosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Peritoneal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Avelumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>No IPD will be shared.</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03252938
org study id: INSIGHT
nct id: NCT03252938
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This phase I trial aims to investigate a potential enhancement of IMP321 immune-activating
      effects by new routes of administration: direct injection of IMP321 into the tumor tissue;
      intra-peritoneal therapy; combination of chemotherapy and/or immunotherapy/targeted therapy
      with active immunotherapy
Up to now, IMP321 is solely administered by sub-cutaneous injection (e.g. on the anterior
      face of the thigh). In this study, we investigate whether a direct injection of IMP321 into
      the tumor tissue will be a useful option to improve anti-tumor immune response by placing the
      immune-therapeutic agent in direct vicinity of immune infiltrates in the tumor bed. This
      bypasses processes necessary for drug delivery to cells of solid tumors following systemic
      administration, like transport within vessels, transport across vasculature walls into
      surrounding tissues, and - in cases of peritoneal metastases - transport through the
      interstitial space within a tumor. For the latter case, we will also explore if an
      intra-peritoneal therapy represents a feasible alternative by means of delivering high drug
      concentrations directly to tumors located in the peritoneal cavity.

      Furthermore, we will explore the possibility to extend the positive results obtained by
      subcutaneous injections of IMP321 in metastatic renal cell and breast carcinomas to further
      solid tumor entities. In this part of the study, patients will be treated with the
      standard-of-care (SOC) chemotherapy and/or immunotherapy/targeted therapy for their tumor
      entity along with subcutaneous injections of IMP321.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Feasibility rate
time frame: 10 weeks of treatment + 2 weeks of safety observation period
description: Rate of patients receiving the protocol treatment without occurrence of a dose limiting toxicity
measure: Incidence and severity of adverse events according to CTC criteria
time frame: 12 months of treatment + 12 months of Follow Up
description: Incidence and severity of adverse events according to the current National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).
measure: Response
time frame: 12 months of Follow Up
description: Objective response rate according to RECIST 1.1 and endoscopic response criteria
measure: Progression free survival
time frame: 12 months of Follow Up
description: PFS will be measured as time from inclusion until disease progression or death of any cause
measure: Overall survival
time frame: 12 months of Follow Up
description: OS will be measured as time from inclusion to death of any cause
measure: Immune response in whole blood and tumor tissue
time frame: 12 months of treatment + 12 months of Follow Up
description: Peripheral blood monocyte number and CD8 T-cell number, associated activation markers, tumor-infiltrating immune cells
arm group label: Solid tumors
arm group type: Experimental
description: Biweekly intra-tumoral injections of escalating doses (6 mg, 12 mg, 24 mg and 30 mg) of IMP321 as a monotherapy (intratumoral injections in parenchymatous organs (e.g. liver, spleen, adrenal gland, pancreas) are not allowed)
arm group label: Solid tumors + peritoneal carcinomatosis
arm group type: Experimental
description: Biweekly intra-peritoneal, escalating doses of IMP321 (1 mg, 3 mg, 6 mg, 12 mg and 30 mg)
arm group label: Solid tumors + chemotherapy
arm group type: Experimental
description: Subcutaneous (s.c.) injections with the optimal dose of IMP321 defined in the AIPAC trial for a maximum of 24 weeks
arm group label: Solid tumors + Avelumab/IMP321 therapy
arm group type: Experimental
description: Avelumab and IMP321 as follows:
800 mg avelumab every 2 weeks i.v. (for a maximum of 24 cycles [48 weeks])
6 mg (cohort 1) or 30 mg (cohort 2) IMP321 every 2 weeks s.c. (for a maximum of 12 cycles [24 weeks])
arm group label: Solid tumors + Avelumab/IMP321 combination therapy
arm group type: Experimental
description: Avelumab and IMP321 as follows:
• 800 mg avelumab every 2 weeks i.v. and 30 mg IMP321 every 2 weeks s.c. for a maximum of 24 cycles [12 months]
intervention type: Drug
intervention name: IMP321
description: LAG-3Ig fusion protein, highly potent activator of antigen presenting cells
arm group label: Solid tumors
arm group label: Solid tumors + Avelumab/IMP321 combination therapy
arm group label: Solid tumors + Avelumab/IMP321 therapy
arm group label: Solid tumors + chemotherapy
arm group label: Solid tumors + peritoneal carcinomatosis
other name: LAG-3Ig fusion protein
intervention type: Drug
intervention name: Avelumab
description: Avelumab i.v.
arm group label: Solid tumors + Avelumab/IMP321 combination therapy
arm group label: Solid tumors + Avelumab/IMP321 therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Thorsten Götze, MD
role: Principal Investigator
affiliation: Institute of Clinical Cancer Research (IKF), UCT Frankfurt, Germany
last name: Salah-Eddin Al-Batran, MD
phone: +49 69 7601
phone ext: 4420
email: albatran@ikf-khnw.de
last name: Sabine Beck, PhD
phone: +49 69 7601
phone ext: 3955
email: beck.sabine@ikf-khnw.de
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: Germany
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Peritoneal Neoplasms
mesh term: Avelumab
sharing ipd: No
ipd description: No IPD will be shared.