<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/NCT03816358</url>
  </required_header>
  <id_info>
    <org_study_id>NCI-2019-00242</org_study_id>
    <secondary_id>NCI-2019-00242</secondary_id>
    <secondary_id>PJC-026</secondary_id>
    <secondary_id>10208</secondary_id>
    <secondary_id>10208</secondary_id>
    <secondary_id>UM1CA186644</secondary_id>
    <nct_id>NCT03816358</nct_id>
  </id_info>
  <brief_title>Testing the Combination of Anetumab Ravtansine With Either Nivolumab, Nivolumab and Ipilimumab, or Gemcitabine and Nivolumab in Advanced Pancreatic Cancer</brief_title>
  <official_title>A Phase I Study of Anetumab Ravtansine in Combination With Either Anti-PD-1 Antibody, or Anti-CTLA4 and Anti-PD-1 Antibodies or Anti-PD-1 Antibody and Gemcitabine in Mesothelin-Positive Advanced Pancreatic Adenocarcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Cancer Institute (NCI)</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase I trial studies the side effects and best dose of anetumab ravtansine when given&#xD;
      together with nivolumab, ipilimumab and gemcitabine hydrochloride in treating patients with&#xD;
      mesothelin positive pancreatic cancer that has spread to other places in the body (advanced).&#xD;
      Anetumab ravtansine is a monoclonal antibody, called anetumab ravtansine, linked to a&#xD;
      chemotherapy drug called DM4. Anetumab attaches to mesothelin positive cancer cells in a&#xD;
      targeted way and delivers DM4 to kill them. Immunotherapy with monoclonal antibodies, such as&#xD;
      nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may&#xD;
      interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as&#xD;
      gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either&#xD;
      by killing the cells, by stopping them from dividing, or by stopping them from spreading.&#xD;
      Giving anetumab ravtansine together with nivolumab, ipilimumab, and gemcitabine hydrochloride&#xD;
      may work better in treating patients with pancreatic cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. To evaluate the safety and tolerability of anetumab ravtansine with the following&#xD;
      combinations in patients with mesothelin positive pancreatic adenocarcinoma.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To assess the preliminary anti-tumor activity of anetumab ravtansine (anetumab) in&#xD;
      combination with nivolumab, nivolumab and ipilimumab, nivolumab and gemcitabine hydrochloride&#xD;
      (gemcitabine) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1&#xD;
      overall response rate (ORR).&#xD;
&#xD;
      II. To characterize the pharmacokinetics (PK) profile of anetumab (apparent diffusion&#xD;
      coefficient [ADC]), total antibody (ADC and cleaved free antibody), DM4 and DM4-Me (S-Methyl&#xD;
      metabolite of DM4).&#xD;
&#xD;
      III. To evaluate the tumor microenvironment and immune changes in tumor and peripheral blood&#xD;
      over the course of treatment to identify predictors of response or resistance to treatment.&#xD;
&#xD;
      IV. To measure the progressive disease (PD) effects of this combination including molecular&#xD;
      and immune biomarkers in tumor biopsies and peripheral blood.&#xD;
&#xD;
      EXPLORATORY OBJECTIVES:&#xD;
&#xD;
      I. To characterize mesothelin, PD-L1, CD3, CD4, CD8 expressions at baseline and after&#xD;
      treatment in mesothelin positive pancreatic cancer patients.&#xD;
&#xD;
      II. To evaluate level of soluble mesothelin and megakaryocyte potentiation factor (MPF) over&#xD;
      the course of treatment and to correlate these biomarkers with clinical outcome.&#xD;
&#xD;
      III. To perform whole exome sequencing (WES) +/- ribonucleic acid sequencing (RNAseq) in the&#xD;
      tumor biopsy specimens and correlation genomic (e.g. mutational burden) and transcriptomic&#xD;
      biomarkers with clinical outcome.&#xD;
&#xD;
      IV. To evaluate mononuclear phagocyte system (MPS) function, Fc-gamma receptors (FcgammaRs)&#xD;
      and hormone and chemokine mediators as methods to evaluate factors affecting the PK and PD of&#xD;
      these agents.&#xD;
&#xD;
      V. To evaluate anti-drug antibody (ADA) titres changes pre and post treatment and correlate&#xD;
      them with PK, toxicity and responses.&#xD;
&#xD;
      OUTLINE: This is a dose-escalation study of anetumab ravtansine. Patients are assigned to 1&#xD;
      of 3 arms.&#xD;
&#xD;
      ARM I: Patients receive anetumab ravtansine intravenously (IV) over 1 hour on day 1 and&#xD;
      nivolumab IV over 30 minutes on day 8 of cycle 1 and on day 1 of subsequent cycles. Treatment&#xD;
      repeats every 21 or 28 days (cycle 1) for up to 17 cycles in the absence of disease&#xD;
      progression or unacceptable toxicity. Patients also undergo a biopsy and collection of blood&#xD;
      on study.&#xD;
&#xD;
      ARM II: Patients receive anetumab ravtansine IV over 1 hour on day 1 and nivolumab IV over 30&#xD;
      minutes on day 8 of cycle 1 and on day 1 of subsequent cycles. Patients also receive&#xD;
      ipilimumab IV over 30 minutes on day 8 of cycle 1 and on day 1 of cycles 2-4. Treatment&#xD;
      repeats every 21 or 28 days (cycle 1) for up to 17 cycles in the absence of disease&#xD;
      progression or unacceptable toxicity. Patients also undergo a biopsy and collection of blood&#xD;
      on study.&#xD;
&#xD;
      ARM III: Patients receive anetumab ravtansine IV over 1 hour on day 1 and nivolumab IV over&#xD;
      30 minutes on day 8 of cycle 1 and on day 1 of subsequent cycles. Patients also receive&#xD;
      gemcitabine hydrochloride over 30-40 minutes on days 1 and 8. Treatment repeats every 21 or&#xD;
      28 days (cycle 1) for up to 17 cycles in the absence of disease progression or unacceptable&#xD;
      toxicity. Patients also undergo a biopsy and collection of blood on study.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 8 weeks for up to 100&#xD;
      days, then every 12 weeks thereafter.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 28, 2019</start_date>
  <completion_date type="Anticipated">January 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">January 31, 2024</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum tolerated dose (MTD)</measure>
    <time_frame>Up to 30-37 days post treatment</time_frame>
    <description>This study will follow a 3+3 dose escalation design.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Biomarker analysis</measure>
    <time_frame>Up to 100 days post treatment</time_frame>
    <description>The analysis on proposed biomarkers is hypothesis generating in nature. Descriptive statistics will be used for analysis of biomarkers. The key biomarker is CD8. CD8 after anetumab will be compared with CD8 after immunotherapy. Paired T-test will be carried out to identify changes in each biomarker between time points and mixed model will be used to study the trend in biomarkers over time when multiple measurements are available. The association between baseline biomarkers or change in biomarkers and clinical outcome progression-free survival, toxicity and overall response will also be analyzed by Cox model or logistic model where appropriate. The results may be adjusted using Pocock method for multiplicity.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">74</enrollment>
  <condition>Metastatic Pancreatic Adenocarcinoma</condition>
  <condition>Recurrent Pancreatic Adenocarcinoma</condition>
  <condition>Stage II Pancreatic Cancer AJCC v8</condition>
  <condition>Stage III Pancreatic Cancer AJCC v8</condition>
  <condition>Stage IV Pancreatic Cancer AJCC v8</condition>
  <condition>Unresectable Pancreatic Carcinoma</condition>
  <arm_group>
    <arm_group_label>Arm I (anetumab ravtansine, nivolumab)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive anetumab ravtansine IV over 1 hour on day 1 and nivolumab IV over 30 minutes on day 8 of cycle 1 and on day 1 of subsequent cycles. Treatment repeats every 21 or 28 days (cycle 1) for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo a biopsy and collection of blood on study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm II (anetumab ravtansine, nivolumab, ipilimumab)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive anetumab ravtansine IV over 1 hour on day 1 and nivolumab IV over 30 minutes on day 8 of cycle 1 and on day 1 of subsequent cycles. Patients also receive ipilimumab IV over 30 minutes on day 8 of cycle 1 and on day 1 of cycles 2-4. Treatment repeats every 21 or 28 days (cycle 1) for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo a biopsy and collection of blood on study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm III (anetumab ravtansine, nivolumab, gemcitabine)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive anetumab ravtansine IV over 1 hour on day 1 and nivolumab IV over 30 minutes on day 8 of cycle 1 and on day 1 of subsequent cycles. Patients also receive gemcitabine hydrochloride over 30-40 minutes on days 1 and 8. Treatment repeats every 21 or 28 days (cycle 1) for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo a biopsy and collection of blood on study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Anetumab Ravtansine</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (anetumab ravtansine, nivolumab)</arm_group_label>
    <arm_group_label>Arm II (anetumab ravtansine, nivolumab, ipilimumab)</arm_group_label>
    <arm_group_label>Arm III (anetumab ravtansine, nivolumab, gemcitabine)</arm_group_label>
    <other_name>BAY 94-9343</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Biopsy</intervention_name>
    <description>Undergo biopsy</description>
    <arm_group_label>Arm I (anetumab ravtansine, nivolumab)</arm_group_label>
    <arm_group_label>Arm II (anetumab ravtansine, nivolumab, ipilimumab)</arm_group_label>
    <arm_group_label>Arm III (anetumab ravtansine, nivolumab, gemcitabine)</arm_group_label>
    <other_name>BIOPSY_TYPE</other_name>
    <other_name>Bx</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Biospecimen Collection</intervention_name>
    <description>Undergo collection of blood</description>
    <arm_group_label>Arm I (anetumab ravtansine, nivolumab)</arm_group_label>
    <arm_group_label>Arm II (anetumab ravtansine, nivolumab, ipilimumab)</arm_group_label>
    <arm_group_label>Arm III (anetumab ravtansine, nivolumab, gemcitabine)</arm_group_label>
    <other_name>Biological Sample Collection</other_name>
    <other_name>Biospecimen Collected</other_name>
    <other_name>Specimen Collection</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gemcitabine Hydrochloride</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm III (anetumab ravtansine, nivolumab, gemcitabine)</arm_group_label>
    <other_name>dFdCyd</other_name>
    <other_name>Difluorodeoxycytidine Hydrochloride</other_name>
    <other_name>Gemcitabine HCI</other_name>
    <other_name>Gemzar</other_name>
    <other_name>LY-188011</other_name>
    <other_name>LY188011</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Ipilimumab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm II (anetumab ravtansine, nivolumab, ipilimumab)</arm_group_label>
    <other_name>Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody</other_name>
    <other_name>BMS-734016</other_name>
    <other_name>Ipilimumab Biosimilar CS1002</other_name>
    <other_name>MDX-010</other_name>
    <other_name>MDX-CTLA4</other_name>
    <other_name>Yervoy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Nivolumab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (anetumab ravtansine, nivolumab)</arm_group_label>
    <arm_group_label>Arm II (anetumab ravtansine, nivolumab, ipilimumab)</arm_group_label>
    <arm_group_label>Arm III (anetumab ravtansine, nivolumab, gemcitabine)</arm_group_label>
    <other_name>BMS-936558</other_name>
    <other_name>CMAB819</other_name>
    <other_name>MDX-1106</other_name>
    <other_name>NIVO</other_name>
    <other_name>Nivolumab Biosimilar CMAB819</other_name>
    <other_name>ONO-4538</other_name>
    <other_name>Opdivo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have histologically or cytologically confirmed pancreatic adenocarcinoma&#xD;
             that is metastatic or unresectable or recurrent&#xD;
&#xD;
          -  Only subjects with positive mesothelin expression (Ventana mesothelin [MSLN]-&#xD;
             immunohistochemistry [IHC]; Negative=H-score =&lt; 10) are eligible. This is to be&#xD;
             performed centrally. For dose escalation cohorts, patients with mesothelin expression&#xD;
             in &gt;= 5% of tumor cells are eligible. For dose expansion, patients must have moderate&#xD;
             or strong tumor mesothelin expression defined as &gt;= 30% of tumor cells with mesothelin&#xD;
             expression of 2+/3 on immunohistochemical staining&#xD;
&#xD;
          -  Patients must be &gt;= 18 years of age&#xD;
&#xD;
          -  Patients must have received and either progressed or been intolerant to at least 1&#xD;
             systemic therapy&#xD;
&#xD;
          -  Life expectancy of at least 3 months&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status score 0-1 (Karnofsky &gt;=&#xD;
             80%)&#xD;
&#xD;
          -  Prior anti-cancer treatments are permitted (i.e. chemotherapy, including gemcitabine&#xD;
             and nab-paclitaxel; radiotherapy; hormonal, or immunotherapy with the exception of&#xD;
             anti-CTLA4, anti-PD1/PD-L1, and combination of anti-CTLA4 and anti-PD1/PD-L1)&#xD;
             providing toxicity (except for alopecia) related to prior anti-cancer therapy and/or&#xD;
             surgery have either resolved, improved to baseline or G1&#xD;
&#xD;
          -  At least one (1) measurable lesion at baseline by computed tomography (CT) or magnetic&#xD;
             resonance imaging (MRI) as per RECIST version (v)1.1; measurable disease is a&#xD;
             requirement in both dose escalation phase and dose expansion phase&#xD;
&#xD;
               -  Note: Measurable lesions may be in an irradiated field as long as there is&#xD;
                  documented progression and the lesion(s) can be reproducibly measured&#xD;
&#xD;
          -  At least one lesion safely accessible for biopsy unless medically contraindicated;&#xD;
             biopsies are mandatory both in dose escalation and in dose expansion; in dose&#xD;
             escalation and in expansion the following biopsies are optional: at baseline and at&#xD;
             progression; biopsy could be: core needle or excisional or punch biopsy. Irradiated&#xD;
             lesions can be biopsied if tumor growth is confirmed&#xD;
&#xD;
          -  Patients must have archival tumor tissue for mesothelin expression and correlative&#xD;
             biomarker studies; subjects must consent to provide tumor blocks or slides and the&#xD;
             availability of the tissue must be confirmed prior to subjects receiving study&#xD;
             medication; if an archived tumor specimen is unavailable or unsuitable for correlative&#xD;
             biomarker studies, a pre-treatment fresh tumor biopsy is required&#xD;
&#xD;
          -  Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy&#xD;
             test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin&#xD;
             [HCG]) within 24 hours of study enrollment or randomization; WOCBP must agree to&#xD;
             appropriate methods of contraception for the duration of treatment and for 6 months&#xD;
             after completion of treatment; males who are sexually active with a partner of&#xD;
             childbearing potential must agree to appropriate methods of contraception for the&#xD;
             duration of treatment. For all male patients, prior to treatment, advice should be&#xD;
             sought for conserving sperm due to the chance of irreversible infertility as a&#xD;
             consequence of treatment; genetic consultation is recommended if the patient wishes to&#xD;
             have children after ending treatment; the investigator or a designated associate is&#xD;
             requested to advise the patient how to achieve highly effective birth control&#xD;
&#xD;
               -  Highly effective (failure rate of less than 1% per year) contraception methods&#xD;
                  include:&#xD;
&#xD;
                    -  Combined (estrogen and progesterone containing: oral, intravaginal,&#xD;
                       transdermal) and progesterone-only (oral, injectable, implantable) hormonal&#xD;
                       contraception associated with inhibition of ovulation&#xD;
&#xD;
                    -  Intrauterine device (IUD) or intrauterine hormone-releasing system (IUS)&#xD;
&#xD;
                    -  Bilateral tubal occlusion or vasectomized partner (provided that partner is&#xD;
                       the sole sexual partner and has received medical assessment of the surgical&#xD;
                       success)&#xD;
&#xD;
                    -  Sexual abstinence (reliability to be evaluated in relation to the duration&#xD;
                       of the clinical trial and the preferred and usual lifestyle of the patient)&#xD;
&#xD;
               -  Male patients with a female partner of childbearing potential must use a condom&#xD;
                  and ensure that an additional form of contraception is also used during&#xD;
&#xD;
                    -  Note: a woman is considered WOCBP, i.e. fertile, following menarche and&#xD;
                       until becoming postmenopausal unless permanently sterile; permanent&#xD;
                       sterilization methods include but are not limited to hysterectomy, bilateral&#xD;
                       salpingectomy and bilateral oophorectomy&#xD;
&#xD;
               -  A postmenopausal state is defined as no menses for 12 months without an&#xD;
                  alternative medical cause; a high follicle stimulating hormone (FSH) level in the&#xD;
                  postmenopausal range may be used to confirm a postmenopausal state in women not&#xD;
                  using hormonal contraception or hormonal replacement therapy; a man is considered&#xD;
                  fertile after puberty unless permanently sterile by bilateral orchiectomy&#xD;
&#xD;
          -  Leukocytes &gt;= 3,000/mcL&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1,500/mcL&#xD;
&#xD;
          -  Platelets &gt;= 100,000/mcL&#xD;
&#xD;
          -  Hemoglobin &gt;= 9 g/dL&#xD;
&#xD;
               -  Patients must have not had a transfusion in the 2 weeks preceding this hemoglobin&#xD;
                  (Hb) measurement&#xD;
&#xD;
          -  Total bilirubin =&lt; institutional upper limit of normal (ULN)&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase&#xD;
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])&#xD;
             =&lt; 3 x institutional ULN&#xD;
&#xD;
          -  Creatinine =&lt; institutional ULN OR glomerular filtration rate (GFR) &gt;= 60 mL/min/1.73&#xD;
             m^2 unless data exists supporting safe use at lower kidney function values, no lower&#xD;
             than 30 mL/min/1.73 m^2&#xD;
&#xD;
          -  Albumin &gt;= 2.5 mg/dL&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients not recovered from clinically significant adverse events of their most recent&#xD;
             therapy/intervention prior to enrollment. Concurrent enrollment in a&#xD;
             non-interventional clinical study or the follow-up period of an interventional study&#xD;
             is allowed.&#xD;
&#xD;
          -  Untreated central nervous system (CNS) metastatic disease, leptomeningeal disease, or&#xD;
             cord compression; subjects with previously treated brain metastases may participate&#xD;
             provided they are stable (without evidence of progression by imaging for at least six&#xD;
             weeks prior to the first dose of trial treatment and any neurologic symptoms have&#xD;
             returned to baseline), have no evidence of new or enlarging brain metastases, and are&#xD;
             not using steroids for at least 14 days prior to trial treatment&#xD;
&#xD;
          -  Evidence of uncontrolled, active infection, requiring parenteral anti-bacterial,&#xD;
             anti-viral or anti-fungal therapy (washout: 7 days prior to cycle 1 day 1 [C1D1])&#xD;
&#xD;
          -  Patients are prohibited from receiving the following therapies during the screening&#xD;
             and treatment phase of this trial:&#xD;
&#xD;
               -  Antineoplastic systemic chemotherapy or biological therapy&#xD;
&#xD;
               -  Radiation therapy&#xD;
&#xD;
                    -  Note: Radiation therapy to a symptomatic solitary lesion or to the brain may&#xD;
                       be considered on an exceptional case by case basis after consultation with&#xD;
                       Cancer Therapy Evaluation Program (CTEP); the patient must have clear&#xD;
                       measurable disease outside the radiated field; administration of palliative&#xD;
                       radiation therapy will be considered clinical progression for the purposes&#xD;
                       of determining progression free survival (PFS)&#xD;
&#xD;
               -  Live vaccines within 30 days prior to the first dose of trial treatment and while&#xD;
                  participating in the trial; examples of live vaccines include, but are not&#xD;
                  limited to, the following: measles, mumps, rubella, chicken pox, yellow fever,&#xD;
                  rabies, Bacillus Chalmette-Guerin (BCG), typhoid (oral) vaccine, and intranasal&#xD;
                  influenza vaccines (e.g., Flu-Mist)&#xD;
&#xD;
          -  Current or prior use of systemic immunosuppressive medication (except corticosteroids&#xD;
             at physiological doses, not exceeding 10 mg prednisone-equivalent day) within 10 days&#xD;
             before the first dose of study medication; intranasal, inhaled, topical, or local&#xD;
             steroid injections are allowed; steroids as premedication for hypersensitivity&#xD;
             reactions (i.e. CT scan premedication) are allowed; systemic glucocorticoids used to&#xD;
             modulate symptoms from an event of suspected immunologic etiology are permitted&#xD;
&#xD;
          -  Any major surgery within 4 weeks of study drug administration&#xD;
&#xD;
          -  Concomitant second malignancies (except adequately treated squamous cell carcinoma&#xD;
             [SCC] or basal cell carcinoma [BCC] skin cancers or in situ bladder, breast or&#xD;
             cervical cancers) within the last 3 years prior to study entry&#xD;
&#xD;
          -  Uncontrolled or significant cardiovascular disease, including but not limited to&#xD;
             ongoing or active symptomatic congestive heart failure, uncontrolled hypertension,&#xD;
             unstable angina pectoris, unstable cardiac arrhythmia&#xD;
&#xD;
          -  National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)&#xD;
             version (v)5 &gt;= grade (G)2 peripheral neuropathy (sensory or motor)&#xD;
&#xD;
          -  Patients with corneal epitheliopathy and at the discretion of the ophthalmologist any&#xD;
             other eye disorder&#xD;
&#xD;
               -  Note: Low grades of superficial punctate keratitis, within the range seen in the&#xD;
                  normal population, should not lead to the exclusion of the patient&#xD;
&#xD;
          -  Active or prior documented inflammatory bowel disease (i.e. ulcerative colitis)&#xD;
&#xD;
          -  Active or prior documented autoimmune disease within the past 2 years&#xD;
&#xD;
               -  Note: subjects with vitiligo, Grave's disease, psoriasis not requiring systemic&#xD;
                  treatment or hypothyroidism (i.e. following Hashimoto syndrome) stable on hormone&#xD;
                  replacement are not excluded&#xD;
&#xD;
          -  Recent history or current evidence of bleeding disorder (i.e. any CTCAE G &gt;= 2&#xD;
             hemorrhage/bleeding event within 28 days before the start of treatment)&#xD;
&#xD;
          -  Active human immunodeficiency virus (HIV), hepatitis B or C infection; HIV-positive&#xD;
             patients on antiretroviral therapy with undetectable viral load will not be excluded&#xD;
             from the trial; subjects with treated hepatitis B or C with unquantifiable viral loads&#xD;
             and no organ compromise are not excluded&#xD;
&#xD;
          -  Any condition that, in the opinion of the investigator, would interfere with&#xD;
             evaluation of study treatment or interpretation of patient safety or study results&#xD;
&#xD;
          -  Pregnant women are excluded from this study because of the potential for teratogenic&#xD;
             or abortifacient effects; because there is an unknown but potential risk for adverse&#xD;
             events in nursing infants secondary to treatment of the mother, breastfeeding should&#xD;
             be discontinued for at least 6 months after last dose of study drugs; these potential&#xD;
             risks may also apply to other agents used in this study; should a patient become&#xD;
             pregnant or suspect she is pregnant while she is participating in this study, the&#xD;
             patient should inform the treating physician immediately&#xD;
&#xD;
          -  Participants who have had prior organ transplants (i.e. renal, lung, heart) due to the&#xD;
             potential for increased rejection with immunotherapy&#xD;
&#xD;
          -  Patients taking strong CYP3A4 inhibitors or strong CYP3A4 inducers within 2 weeks&#xD;
             before the start of study treatment are excluded; consumption of grapefruit or its&#xD;
             juice, and other fruit/juices which are strong CYP3A4 inhibitors within 2 weeks of&#xD;
             study treatment is also not permitted; examples of strong CYP3A4 inhibitors include&#xD;
             the following: indinavir, ritonavir, clarithromycin, itraconazole, ketoconazole,&#xD;
             nefazodone, and saquinavir; examples of strong CYP3A4 inducers include the following:&#xD;
             carbamazepine, rifampin, phenytoin, St. John's wort, and phenobarbital; these lists&#xD;
             are not exhaustive&#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>Anna Spreafico</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Health Network Princess Margaret Cancer Center LAO</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Alabama at Birmingham Cancer Center</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35233</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City of Hope Comprehensive Cancer Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City of Hope at Irvine Lennar</name>
      <address>
        <city>Irvine</city>
        <state>California</state>
        <zip>92618</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Keck Medicine of USC Koreatown</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90020</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Los Angeles County-USC Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>USC / Norris Comprehensive Cancer Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UC Irvine Health/Chao Family Comprehensive Cancer Center</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California Davis Comprehensive Cancer Center</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCHealth University of Colorado Hospital</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UM Sylvester Comprehensive Cancer Center at Coral Gables</name>
      <address>
        <city>Coral Gables</city>
        <state>Florida</state>
        <zip>33146</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UM Sylvester Comprehensive Cancer Center at Deerfield Beach</name>
      <address>
        <city>Deerfield Beach</city>
        <state>Florida</state>
        <zip>33442</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Miami Miller School of Medicine-Sylvester Cancer Center</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UM Sylvester Comprehensive Cancer Center at Plantation</name>
      <address>
        <city>Plantation</city>
        <state>Florida</state>
        <zip>33324</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Clinical Research Center</name>
      <address>
        <city>Fairway</city>
        <state>Kansas</state>
        <zip>66205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HaysMed University of Kansas Health System</name>
      <address>
        <city>Hays</city>
        <state>Kansas</state>
        <zip>67601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Cancer Center</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lawrence Memorial Hospital</name>
      <address>
        <city>Lawrence</city>
        <state>Kansas</state>
        <zip>66044</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Olathe Health Cancer Center</name>
      <address>
        <city>Olathe</city>
        <state>Kansas</state>
        <zip>66061</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Cancer Center-Overland Park</name>
      <address>
        <city>Overland Park</city>
        <state>Kansas</state>
        <zip>66210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Hospital-Indian Creek Campus</name>
      <address>
        <city>Overland Park</city>
        <state>Kansas</state>
        <zip>66211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ascension Via Christi - Pittsburg</name>
      <address>
        <city>Pittsburg</city>
        <state>Kansas</state>
        <zip>66762</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Salina Regional Health Center</name>
      <address>
        <city>Salina</city>
        <state>Kansas</state>
        <zip>67401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Health System Saint Francis Campus</name>
      <address>
        <city>Topeka</city>
        <state>Kansas</state>
        <zip>66606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Hospital-Westwood Cancer Center</name>
      <address>
        <city>Westwood</city>
        <state>Kansas</state>
        <zip>66205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kentucky/Markey Cancer Center</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40536</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wayne State University/Karmanos Cancer Institute</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Weisberg Cancer Treatment Center</name>
      <address>
        <city>Farmington Hills</city>
        <state>Michigan</state>
        <zip>48334</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Siteman Cancer Center at West County Hospital</name>
      <address>
        <city>Creve Coeur</city>
        <state>Missouri</state>
        <zip>63141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Truman Medical Centers</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Cancer Center - North</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64154</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Cancer Center - Lee's Summit</name>
      <address>
        <city>Lee's Summit</city>
        <state>Missouri</state>
        <zip>64064</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Cancer Center at North Kansas City Hospital</name>
      <address>
        <city>North Kansas City</city>
        <state>Missouri</state>
        <zip>64116</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Siteman Cancer Center-South County</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63129</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Siteman Cancer Center at Christian Hospital</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Siteman Cancer Center at Saint Peters Hospital</name>
      <address>
        <city>Saint Peters</city>
        <state>Missouri</state>
        <zip>63376</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center</name>
      <address>
        <city>Lebanon</city>
        <state>New Hampshire</state>
        <zip>03756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Laura and Isaac Perlmutter Cancer Center at NYU Langone</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wake Forest University Health Sciences</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27157</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ohio State University Comprehensive Cancer Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University/Ingram Cancer Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>M D Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Huntsman Cancer Institute/University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Health Network-Princess Margaret Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>January 24, 2019</study_first_submitted>
  <study_first_submitted_qc>January 24, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 25, 2019</study_first_posted>
  <last_update_submitted>September 9, 2023</last_update_submitted>
  <last_update_submitted_qc>September 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenocarcinoma</mesh_term>
    <mesh_term>Pancreatic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gemcitabine</mesh_term>
    <mesh_term>Nivolumab</mesh_term>
    <mesh_term>Ipilimumab</mesh_term>
    <mesh_term>Maytansine</mesh_term>
    <mesh_term>Anetumab ravtansine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page</ipd_description>
    <ipd_url>https://grants.nih.gov/policy/sharing.htm</ipd_url>
  </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/NCT03816358
org study id: NCI-2019-00242
secondary id: NCI-2019-00242
secondary id: PJC-026
secondary id: 10208
secondary id: 10208
secondary id: UM1CA186644
nct id: NCT03816358
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This phase I trial studies the side effects and best dose of anetumab ravtansine when given
      together with nivolumab, ipilimumab and gemcitabine hydrochloride in treating patients with
      mesothelin positive pancreatic cancer that has spread to other places in the body (advanced).
      Anetumab ravtansine is a monoclonal antibody, called anetumab ravtansine, linked to a
      chemotherapy drug called DM4. Anetumab attaches to mesothelin positive cancer cells in a
      targeted way and delivers DM4 to kill them. Immunotherapy with monoclonal antibodies, such as
      nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may
      interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as
      gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either
      by killing the cells, by stopping them from dividing, or by stopping them from spreading.
      Giving anetumab ravtansine together with nivolumab, ipilimumab, and gemcitabine hydrochloride
      may work better in treating patients with pancreatic cancer.
PRIMARY OBJECTIVE:

      I. To evaluate the safety and tolerability of anetumab ravtansine with the following
      combinations in patients with mesothelin positive pancreatic adenocarcinoma.

      SECONDARY OBJECTIVES:

      I. To assess the preliminary anti-tumor activity of anetumab ravtansine (anetumab) in
      combination with nivolumab, nivolumab and ipilimumab, nivolumab and gemcitabine hydrochloride
      (gemcitabine) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
      overall response rate (ORR).

      II. To characterize the pharmacokinetics (PK) profile of anetumab (apparent diffusion
      coefficient [ADC]), total antibody (ADC and cleaved free antibody), DM4 and DM4-Me (S-Methyl
      metabolite of DM4).

      III. To evaluate the tumor microenvironment and immune changes in tumor and peripheral blood
      over the course of treatment to identify predictors of response or resistance to treatment.

      IV. To measure the progressive disease (PD) effects of this combination including molecular
      and immune biomarkers in tumor biopsies and peripheral blood.

      EXPLORATORY OBJECTIVES:

      I. To characterize mesothelin, PD-L1, CD3, CD4, CD8 expressions at baseline and after
      treatment in mesothelin positive pancreatic cancer patients.

      II. To evaluate level of soluble mesothelin and megakaryocyte potentiation factor (MPF) over
      the course of treatment and to correlate these biomarkers with clinical outcome.

      III. To perform whole exome sequencing (WES) +/- ribonucleic acid sequencing (RNAseq) in the
      tumor biopsy specimens and correlation genomic (e.g. mutational burden) and transcriptomic
      biomarkers with clinical outcome.

      IV. To evaluate mononuclear phagocyte system (MPS) function, Fc-gamma receptors (FcgammaRs)
      and hormone and chemokine mediators as methods to evaluate factors affecting the PK and PD of
      these agents.

      V. To evaluate anti-drug antibody (ADA) titres changes pre and post treatment and correlate
      them with PK, toxicity and responses.

      OUTLINE: This is a dose-escalation study of anetumab ravtansine. Patients are assigned to 1
      of 3 arms.

      ARM I: Patients receive anetumab ravtansine intravenously (IV) over 1 hour on day 1 and
      nivolumab IV over 30 minutes on day 8 of cycle 1 and on day 1 of subsequent cycles. Treatment
      repeats every 21 or 28 days (cycle 1) for up to 17 cycles in the absence of disease
      progression or unacceptable toxicity. Patients also undergo a biopsy and collection of blood
      on study.

      ARM II: Patients receive anetumab ravtansine IV over 1 hour on day 1 and nivolumab IV over 30
      minutes on day 8 of cycle 1 and on day 1 of subsequent cycles. Patients also receive
      ipilimumab IV over 30 minutes on day 8 of cycle 1 and on day 1 of cycles 2-4. Treatment
      repeats every 21 or 28 days (cycle 1) for up to 17 cycles in the absence of disease
      progression or unacceptable toxicity. Patients also undergo a biopsy and collection of blood
      on study.

      ARM III: Patients receive anetumab ravtansine IV over 1 hour on day 1 and nivolumab IV over
      30 minutes on day 8 of cycle 1 and on day 1 of subsequent cycles. Patients also receive
      gemcitabine hydrochloride over 30-40 minutes on days 1 and 8. Treatment repeats every 21 or
      28 days (cycle 1) for up to 17 cycles in the absence of disease progression or unacceptable
      toxicity. Patients also undergo a biopsy and collection of blood on study.

      After completion of study treatment, patients are followed up every 8 weeks for up to 100
      days, then every 12 weeks thereafter.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerated dose (MTD)
time frame: Up to 30-37 days post treatment
description: This study will follow a 3+3 dose escalation design.
measure: Biomarker analysis
time frame: Up to 100 days post treatment
description: The analysis on proposed biomarkers is hypothesis generating in nature. Descriptive statistics will be used for analysis of biomarkers. The key biomarker is CD8. CD8 after anetumab will be compared with CD8 after immunotherapy. Paired T-test will be carried out to identify changes in each biomarker between time points and mixed model will be used to study the trend in biomarkers over time when multiple measurements are available. The association between baseline biomarkers or change in biomarkers and clinical outcome progression-free survival, toxicity and overall response will also be analyzed by Cox model or logistic model where appropriate. The results may be adjusted using Pocock method for multiplicity.
arm group label: Arm I (anetumab ravtansine, nivolumab)
arm group type: Experimental
description: Patients receive anetumab ravtansine IV over 1 hour on day 1 and nivolumab IV over 30 minutes on day 8 of cycle 1 and on day 1 of subsequent cycles. Treatment repeats every 21 or 28 days (cycle 1) for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo a biopsy and collection of blood on study.
arm group label: Arm II (anetumab ravtansine, nivolumab, ipilimumab)
arm group type: Experimental
description: Patients receive anetumab ravtansine IV over 1 hour on day 1 and nivolumab IV over 30 minutes on day 8 of cycle 1 and on day 1 of subsequent cycles. Patients also receive ipilimumab IV over 30 minutes on day 8 of cycle 1 and on day 1 of cycles 2-4. Treatment repeats every 21 or 28 days (cycle 1) for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo a biopsy and collection of blood on study.
arm group label: Arm III (anetumab ravtansine, nivolumab, gemcitabine)
arm group type: Experimental
description: Patients receive anetumab ravtansine IV over 1 hour on day 1 and nivolumab IV over 30 minutes on day 8 of cycle 1 and on day 1 of subsequent cycles. Patients also receive gemcitabine hydrochloride over 30-40 minutes on days 1 and 8. Treatment repeats every 21 or 28 days (cycle 1) for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo a biopsy and collection of blood on study.
intervention type: Biological
intervention name: Anetumab Ravtansine
description: Given IV
arm group label: Arm I (anetumab ravtansine, nivolumab)
arm group label: Arm II (anetumab ravtansine, nivolumab, ipilimumab)
arm group label: Arm III (anetumab ravtansine, nivolumab, gemcitabine)
other name: BAY 94-9343
intervention type: Procedure
intervention name: Biopsy
description: Undergo biopsy
arm group label: Arm I (anetumab ravtansine, nivolumab)
arm group label: Arm II (anetumab ravtansine, nivolumab, ipilimumab)
arm group label: Arm III (anetumab ravtansine, nivolumab, gemcitabine)
other name: BIOPSY_TYPE
other name: Bx
intervention type: Procedure
intervention name: Biospecimen Collection
description: Undergo collection of blood
arm group label: Arm I (anetumab ravtansine, nivolumab)
arm group label: Arm II (anetumab ravtansine, nivolumab, ipilimumab)
arm group label: Arm III (anetumab ravtansine, nivolumab, gemcitabine)
other name: Biological Sample Collection
other name: Biospecimen Collected
other name: Specimen Collection
intervention type: Drug
intervention name: Gemcitabine Hydrochloride
description: Given IV
arm group label: Arm III (anetumab ravtansine, nivolumab, gemcitabine)
other name: dFdCyd
other name: Difluorodeoxycytidine Hydrochloride
other name: Gemcitabine HCI
other name: Gemzar
other name: LY-188011
other name: LY188011
intervention type: Biological
intervention name: Ipilimumab
description: Given IV
arm group label: Arm II (anetumab ravtansine, nivolumab, ipilimumab)
other name: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
other name: BMS-734016
other name: Ipilimumab Biosimilar CS1002
other name: MDX-010
other name: MDX-CTLA4
other name: Yervoy
intervention type: Biological
intervention name: Nivolumab
description: Given IV
arm group label: Arm I (anetumab ravtansine, nivolumab)
arm group label: Arm II (anetumab ravtansine, nivolumab, ipilimumab)
arm group label: Arm III (anetumab ravtansine, nivolumab, gemcitabine)
other name: BMS-936558
other name: CMAB819
other name: MDX-1106
other name: NIVO
other name: Nivolumab Biosimilar CMAB819
other name: ONO-4538
other name: Opdivo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Anna Spreafico
role: Principal Investigator
affiliation: University Health Network Princess Margaret Cancer Center LAO
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Canada
country: United States
responsible party type: Sponsor
mesh term: Adenocarcinoma
mesh term: Pancreatic Neoplasms
mesh term: Gemcitabine
mesh term: Nivolumab
mesh term: Ipilimumab
mesh term: Maytansine
mesh term: Anetumab ravtansine
sharing ipd: Yes
ipd description: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page
ipd url: https://grants.nih.gov/policy/sharing.htm