<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/NCT03037385</url>
  </required_header>
  <id_info>
    <org_study_id>BO42863</org_study_id>
    <secondary_id>2016-004390-41</secondary_id>
    <secondary_id>BLU-667-1101</secondary_id>
    <nct_id>NCT03037385</nct_id>
  </id_info>
  <brief_title>Phase 1/2 Study of the Highly-selective RET Inhibitor, Pralsetinib (BLU-667), in Participants With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors</brief_title>
  <acronym>ARROW</acronym>
  <official_title>A Phase 1/2 Study of the Highly-selective RET Inhibitor, BLU-667, in Patients With Thyroid Cancer, Non-Small Cell Lung Cancer (NSCLC) and Other Advanced Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hoffmann-La Roche</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hoffmann-La Roche</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase 1/2, open-label, first-in-human (FIH) study designed to evaluate the safety,&#xD;
      tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antineoplastic&#xD;
      activity of pralsetinib (BLU-667) administered orally in participants with medullary thyroid&#xD;
      cancer (MTC), RET-altered NSCLC and other RET-altered solid tumors.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study consists of 2 parts, a dose-escalation part (Phase 1) and an expansion part (Phase&#xD;
      2). Both parts will enroll participants with advanced non-resectable NSCLC, advanced&#xD;
      non-resectable thyroid cancer and other advanced solid tumors that have progressed following&#xD;
      standard systemic therapy, have not adequately responded to standard systemic therapy, or the&#xD;
      participants must be intolerant to or the Investigator has determined that treatment with&#xD;
      standard therapy is not appropriate, or there must be no accepted standard therapy for their&#xD;
      disease.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 17, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>Yes</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Phase 1 (Complete):&#xD;
Advanced MTC, NSCLC or other solid tumor&#xD;
30-600mg (PO QD or BID)&#xD;
Phase 2 (400mg QD):&#xD;
Group 1: RET fusion NSCLC previously treated with a platinum chemotherapy&#xD;
Group 2: RET fusion NSCLC not previously treated for metastatic disease&#xD;
Group 3: MTC previously treated with cabozantinib and/or vandetanib&#xD;
Group 4: MTC not previously treated with cabozantinib or vandetanib&#xD;
Group 5: Other solid tumors with a RET fusion not eligible for any of the other groups and previously treated with SOC or have no acceptable SOC for their tumor type as determined by the investigator&#xD;
Group 6: Any solid tumor with a RET alteration (fusion or mutation) previously treated with a selective RET Inhibitor&#xD;
Group 7: Other solid tumors with a RET mutation previously treated with SOC&#xD;
Group 8: RET fusion NSCLC previously treated with a platinum chemotherapy (China only)&#xD;
Group 9: MTC not previously treated with systemic therapy for advanced or metastatic disease (China only)</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>(Phase 1) Determination of Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Pralsetinib</measure>
    <time_frame>Cycle 1 (28 days) of treatment for MTD and at the end of every cycle (28 days) for RP2D for approximately 12 months or earlier if participant terminates from the study</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>(Phase 1) Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)</measure>
    <time_frame>Every cycle (28 days) for approximately 12 months or earlier if participant terminates from the study, and 30 days after the last dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>(Phase 2) Overall Response Rate (ORR)</measure>
    <time_frame>Approximately every 8 weeks or 16 weeks based on the treatment cycle</time_frame>
    <description>As assessed by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) or Response Assessment in Neuro-Oncology (RANO), as appropriate per tumor type</description>
  </primary_outcome>
  <primary_outcome>
    <measure>(Phase 2) Number of Participants with AEs and SAEs</measure>
    <time_frame>Every cycle (28 days) for approximately 24 months or earlier if participant terminates from the study, and 30 days after the last dose</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>(Phase 1) ORR</measure>
    <time_frame>Approximately every 8 weeks during treatment, 14 days after the last dose, and every 3 months after the last dose (Up to 12 months) in participants without progressive disease</time_frame>
    <description>As assessed by RECIST v1.1 or RANO, as appropriate per tumor type</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(Phase 1) RET Gene Status and Correlation Between RET Gene Status and ORR, CBR, DOR, DCR, PFS and Other Antineoplastic Measures</measure>
    <time_frame>Approximately every 8 weeks or 16 weeks based on the treatment cycle (Up to approximately 12 months)</time_frame>
    <description>Clinical Benefit Rate (CBR), Duration of Response (DOR), Disease Control Rate (DCR), Progression Free Survival (PFS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(Phase 2) CBR</measure>
    <time_frame>Approximately every 8 weeks or 16 weeks based on the treatment cycle</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(Phase 2) DOR</measure>
    <time_frame>Approximately every 8 weeks or 16 weeks based on the treatment cycle</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(Phase 2) DCR</measure>
    <time_frame>Approximately every 8 weeks or 16 weeks based on the treatment cycle</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(Phase 2) PFS</measure>
    <time_frame>Approximately every 8 weeks or 16 weeks based on the treatment cycle (Up to approximately 84 months)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(Phase 2) Overall Survival (OS)</measure>
    <time_frame>Approximately every 8 weeks or 16 weeks based on the treatment cycle (Up to approximately 84 months)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(Phase 2) RET Gene Status and Correlation Between RET Gene Status and ORR, CBR, DOR, DCR and Other Antineoplastic Measures</measure>
    <time_frame>On Day 1 of Cycle 1 (each cycle is of 28 days), 2 and 3 and every other cycle thereafter up to Cycle 13</time_frame>
    <description>RET gene status (i.e. gene fusion partner or primary mutation and, for MTC, whether hereditary or sporadic)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(Phases 1 and 2) Pharmacokinetic Parameters Including Maximum Plasma Drug Concentration (Cmax)</measure>
    <time_frame>Approximately every 2 weeks in Cycle 1 and monthly through Cycle 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(Phases 1 and 2) Pharmacokinetic Parameters Including Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours Postdose (AUC0-24)</measure>
    <time_frame>Approximately every 2 weeks in Cycle 1 and monthly through Cycle 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(Phases 1 and 2) Pharmacokinetic Parameters Including Terminal Elimination Half-life (t1/2)</measure>
    <time_frame>Approximately every 2 weeks in Cycle 1 and monthly through Cycle 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(Phase 2) Electrocardiogram (ECG) Assessment Using QT Analysis</measure>
    <time_frame>Effects of BLU-667 on ECG parameters on Cycle 1 Day 1 and Cycle 1 Day 15</time_frame>
    <description>Will be measured from lead II and will be corrected for heart rate (QTc)n using Fridericia's correction factors</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(Phases 1 and 2) Pharmacodynamic Parameters Including Changes in Blood Calcitonin</measure>
    <time_frame>Approximately every 2 weeks in Cycle 1 and monthly through Cycle 3 and every other month through Cycle 13</time_frame>
    <description>MTC participants only</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(Phases 1 and 2) Pharmacodynamic Parameters Including Tumor Marker, Carcinoembryonic Antigen (CEA)</measure>
    <time_frame>Approximately every 2 weeks in Cycle 1 and monthly through Cycle 3 and every other month through Cycle 13</time_frame>
    <description>MTC participants only</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(Phase 2) Assess Intracranial Response Rate and Time to Intracranial Progression in Participants With NSCLC</measure>
    <time_frame>Approximately every 8 weeks or 16 weeks based on the treatment cycle</time_frame>
    <description>Target by RECIST v1.1 or RANO</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">589</enrollment>
  <condition>RET-altered Non Small Cell Lung Cancer</condition>
  <condition>Medullary Thyroid Cancer</condition>
  <condition>RET-altered Papillary Thyroid Cancer</condition>
  <condition>RET-altered Colon Cancer</condition>
  <condition>RET-altered Solid Tumors</condition>
  <condition>Lung Neoplasm</condition>
  <condition>Carcinoma, Non-Small-Cell Lung</condition>
  <condition>Thyroid Diseases</condition>
  <condition>Thyroid Neoplasm</condition>
  <condition>Thyroid Cancer, Papillary</condition>
  <condition>Carcinoma, Neuroendocrine</condition>
  <condition>Respiratory Tract Neoplasms</condition>
  <condition>Thoracic Neoplasms</condition>
  <condition>Neoplasms by Site</condition>
  <condition>Neoplasms</condition>
  <condition>Lung Diseases</condition>
  <condition>Respiratory Tract Disease</condition>
  <condition>Carcinoma, Bronchogenic</condition>
  <condition>Bronchial Neoplasms</condition>
  <condition>Endocrine System Diseases</condition>
  <condition>Endocrine Gland Neoplasm</condition>
  <condition>Head and Neck Neoplasms</condition>
  <condition>Adenocarcinoma, Papillary</condition>
  <condition>Adenocarcinoma</condition>
  <condition>Carcinoma</condition>
  <condition>Neoplasms, Glandular and Epithelial</condition>
  <condition>Neoplasms by Histologic Type</condition>
  <condition>Neuroendocrine Tumors</condition>
  <condition>Neuroectodermal Tumors</condition>
  <condition>Neoplasms, Germ Cell and Embryonal</condition>
  <condition>Neoplasms, Nerve Tissue</condition>
  <condition>Colonic Neoplasms</condition>
  <condition>Colorectal Neoplasms</condition>
  <condition>Intestinal Neoplasms</condition>
  <condition>Gastrointestinal Neoplasms</condition>
  <condition>Digestive System Neoplasm</condition>
  <condition>Digestive System Disease</condition>
  <condition>Gastrointestinal Disease</condition>
  <condition>Colonic Diseases</condition>
  <condition>Intestinal Disease</condition>
  <arm_group>
    <arm_group_label>Phase 1 Dose Escalation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Multiple doses of pralsetinib (BLU-667) for oral administration.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 2 Dose Expansion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral dose of pralsetinib (BLU-667) as determined during Dose Escalation.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>pralsetinib (BLU-667)</intervention_name>
    <description>pralsetinib (BLU-667) is a potent and selective inhibitor of the RET mutations, fusions, and predicted resistant mutants</description>
    <arm_group_label>Phase 1 Dose Escalation</arm_group_label>
    <arm_group_label>Phase 2 Dose Expansion</arm_group_label>
    <other_name>BLU-667</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis during dose escalation (Phase 1) - Pathologically documented, definitively&#xD;
             diagnosed non-resectable advanced solid tumor.&#xD;
&#xD;
               -  All participants treated at doses &gt; 120 mg per day must have MTC, or a&#xD;
                  RET-altered solid tumor per local assessment of tumor tissue and/or blood.&#xD;
&#xD;
          -  Diagnosis during dose expansion (Phase 2) - All participants (with the exception of&#xD;
             participants with MTC enrolled in Groups 3, 4, and 9) must have an oncogenic&#xD;
             RET-rearrangement/fusion or mutation (excluding synonymous, frameshift, and nonsense&#xD;
             mutations) solid tumor, as determined by local or central testing of tumor or&#xD;
             circulating tumor nucleic acid in blood; as detailed below.&#xD;
&#xD;
               -  Group 1 - participants must have pathologically documented, definitively&#xD;
                  diagnosed locally advanced or metastatic NSCLC with a RET fusion previously&#xD;
                  treated with a platinum-based chemotherapy.&#xD;
&#xD;
               -  Group 2 - participants must have pathologically documented, definitively&#xD;
                  diagnosed locally advanced or metastatic NSCLC with a RET fusion not previously&#xD;
                  treated with a platinum-based chemotherapy, including those who have not had any&#xD;
                  systemic therapy. Prior platinum chemotherapy in the neoadjuvant and adjuvant&#xD;
                  setting is permitted if the last dose of platinum was 4 months or more before the&#xD;
                  first dose of study drug.&#xD;
&#xD;
               -  Group 3 - participants must have pathologically documented, definitively&#xD;
                  diagnosed advanced MTC that had progressed within 14 months prior to the&#xD;
                  Screening Visit and was previously treated with cabozantinib and/or vandetanib.&#xD;
&#xD;
               -  Group 4 - participants must have pathologically documented, definitively&#xD;
                  diagnosed advanced MTC that had progressed within 14 months prior to the&#xD;
                  Screening Visit and was not previously treated with cabozantinib and/or&#xD;
                  vandetanib.&#xD;
&#xD;
               -  Group 5 - participants must have a pathologically documented, definitively&#xD;
                  diagnosed advanced solid tumor with an oncogenic RET fusion, have previously&#xD;
                  received standard of care (SOC) appropriate for their tumor type (unless there is&#xD;
                  no accepted standard therapy for the tumor type or the Investigator has&#xD;
                  determined that treatment with standard therapy is not appropriate), and must not&#xD;
                  have been eligible for any of the other groups.&#xD;
&#xD;
               -  Group 6 - participants must have a pathologically documented, definitively&#xD;
                  diagnosed advanced solid tumor with an oncogenic RET fusion or mutation that was&#xD;
                  previously treated with a selective tyrosine kinase inhibitor (TKI) that inhibits&#xD;
                  RET&#xD;
&#xD;
               -  Group 7 - participants must have a pathologically documented, definitively&#xD;
                  diagnosed advanced solid tumor with an oncogenic RET mutation previously treated&#xD;
                  with SOC appropriate for the tumor type and not eligible for any of the other&#xD;
                  groups&#xD;
&#xD;
               -  Group 8 - participants must have pathologically documented, definitively&#xD;
                  diagnosed locally advanced or metastatic NSCLC with a RET fusion that was&#xD;
                  previously treated with a platinum based chemotherapy (China only).&#xD;
&#xD;
               -  Group 9 - participants must have pathologically documented, definitively&#xD;
                  diagnosed advanced MTC that had progressed within 14 months prior to the&#xD;
                  Screening Visit, and was not previously treated with systemic therapy (except&#xD;
                  prior cytotoxic chemotherapy is allowed) for advanced or metastatic disease&#xD;
                  (China only).&#xD;
&#xD;
          -  Participants must have non-resectable disease.&#xD;
&#xD;
          -  Dose expansion (Phase 2): Participants in all groups (except Group 7) must have&#xD;
             measurable disease per RECIST v1.1 (or RANO, criteria if appropriate for tumor type).&#xD;
&#xD;
          -  Participants agrees to provide tumor tissue (archived, if available or a fresh biopsy)&#xD;
             for RET status confirmation and is willing to consider an on-treatment tumor biopsy,&#xD;
             if considered safe and medically feasible by the treating Investigator. For Phase 2,&#xD;
             Group 6, participants are required to undergo a pretreatment biopsy to define baseline&#xD;
             RET status in tumor tissue.&#xD;
&#xD;
          -  Participants has Eastern Cooperative Oncology Group (ECOG) performance status (PS) of&#xD;
             0-1.&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Participant's cancer has a known primary driver alteration other than RET. For&#xD;
             example, NSCLC with a targetable mutation in EGFR, ALK, ROS1 or BRAF; colorectal with&#xD;
             an oncogenic KRAS, NRAS, or BRAF mutation.&#xD;
&#xD;
          -  Participants had any of the following within 14 days prior to the first dose of study&#xD;
             drug:&#xD;
&#xD;
               1. Platelet count &lt; 75 × 10^9/L.&#xD;
&#xD;
               2. Absolute neutrophil count &lt; 1.0 × 10^9/L.&#xD;
&#xD;
               3. Hemoglobin &lt; 9.0 g/dL (red blood cell transfusion and erythropoietin may be used&#xD;
                  to reach at least 9.0 g/dL, but must have been administered at least 2 weeks&#xD;
                  prior to the first dose of study drug.&#xD;
&#xD;
               4. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) &gt; 3 × the&#xD;
                  upper limit of normal (ULN) if no hepatic metastases are present; &gt; 5 × ULN if&#xD;
                  hepatic metastases are present.&#xD;
&#xD;
               5. Total bilirubin &gt; 1.5 × ULN; &gt; 3 × ULN with direct bilirubin &gt; 1.5 × ULN in&#xD;
                  presence of Gilbert's disease.&#xD;
&#xD;
               6. Estimated (Cockcroft-Gault formula) or measured creatinine clearance &lt; 40 mL/min.&#xD;
&#xD;
               7. Total serum phosphorus &gt; 5.5 mg/dL&#xD;
&#xD;
          -  QT interval corrected using Fridericia's formula (QTcF) &gt; 470 msec or history of&#xD;
             prolonged QT syndrome or Torsades de pointes, or familial history of prolonged QT&#xD;
             syndrome.&#xD;
&#xD;
          -  Clinically significant, uncontrolled, cardiovascular disease.&#xD;
&#xD;
          -  Central nervous system (CNS) metastases or a primary CNS tumor that is associated with&#xD;
             progressive neurological symptoms.&#xD;
&#xD;
          -  Clinically symptomatic interstitial lung disease or interstitial pneumonitis including&#xD;
             radiation pneumonitis&#xD;
&#xD;
          -  Participants in Groups 1-5 and 7 (Phase 2) previously treated with a selective RET&#xD;
             inhibitor&#xD;
&#xD;
          -  Participant had a major surgical procedure within 14 days of the first dose of study&#xD;
             drug&#xD;
&#xD;
          -  Participant had a history of another primary malignancy that had been diagnosed or&#xD;
             required therapy within the a year prior to the study&#xD;
&#xD;
          -  Pregnant or breastfeeding female participants&#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>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Hoffmann-La Roche</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic Hospital</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85054</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UC Irvine Medical Center</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado Anschutz Medical Campus</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Georgetown University Medical Center</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic-Jacksonville</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sylvester Comprehensive Cancer Center; University of Miami School of Medicine</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maryland Oncology Hematology, P.A.</name>
      <address>
        <city>Columbia</city>
        <state>Maryland</state>
        <zip>21044</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital.</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109-0934</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55902</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine in St. Louis</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Albany Medical Center</name>
      <address>
        <city>Albany</city>
        <state>New York</state>
        <zip>12208</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Weill Cornell Medical College-New York Presbyterian Hospital</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Health &amp; Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stellar - Chance Laboratories</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology-Austin Midtown</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology - Baylor Charles A. Sammons Cancer Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Texas MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030-4009</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seattle Cancer Care Alliance</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Antwerp University Hospital</name>
      <address>
        <city>Edegem</city>
        <zip>2650</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beijing Cancer Hospital</name>
      <address>
        <city>Beijing</city>
        <zip>100142</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The affiliated Cancer Hospital, School of Medicine, UESTC</name>
      <address>
        <city>Chengdu</city>
        <zip>610041</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>West China Hospital, Sichuan University</name>
      <address>
        <city>Chengdu</city>
        <zip>610041</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chongqing Cancer Hospital</name>
      <address>
        <city>Chongqing</city>
        <zip>400030</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fujian Provincial Cancer Hospital</name>
      <address>
        <city>Fuzhou City</city>
        <zip>350014</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>First Affiliated Hospital of Gannan Medical University</name>
      <address>
        <city>Ganzhou</city>
        <zip>341000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sun Yet-sen University Cancer Center</name>
      <address>
        <city>Guangzhou City</city>
        <zip>510663</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Guangdong General Hospital</name>
      <address>
        <city>Guangzhou</city>
        <zip>510080</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zhejiang Provincial People?s Hospital</name>
      <address>
        <city>Hangzhou</city>
        <zip>310014</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jinan Central Hospital</name>
      <address>
        <city>Jinan City</city>
        <zip>250013</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gansu Cancer Hospital</name>
      <address>
        <city>Lanzhou</city>
        <zip>730050</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fudan University Shanghai Cancer Center</name>
      <address>
        <city>Shanghai City</city>
        <zip>200120</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tianjin Medical University Cancer Institute &amp; Hospital</name>
      <address>
        <city>Tianjing</city>
        <zip>300060</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Union Hospital Tongji Medical College Huazhong University of Science and Technology</name>
      <address>
        <city>Wuhan City</city>
        <zip>430022</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zhejiang Cancer Hospital</name>
      <address>
        <city>Zhejiang</city>
        <zip>310022</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henan Cancer Hospital</name>
      <address>
        <city>Zhengzhou</city>
        <zip>450008</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Bergonie</name>
      <address>
        <city>Bordeaux</city>
        <zip>33076</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Régional Universitaire de Lille (CHRU) - Hôpital Claude Huriez</name>
      <address>
        <city>Lille</city>
        <zip>59037</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Léon Bérard</name>
      <address>
        <city>Lyon</city>
        <zip>69373</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Antoine Lacassagne</name>
      <address>
        <city>Nice</city>
        <zip>06189</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Curie</name>
      <address>
        <city>Paris</city>
        <zip>75005</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Rennes - Hopital de Pontchaillo</name>
      <address>
        <city>Rennes</city>
        <zip>35033</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Larrey;Université Paul Sabatier</name>
      <address>
        <city>Toulouse</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gustave Roussy</name>
      <address>
        <city>Villejuif</city>
        <zip>94805</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Helios Klinikum Emil von Behring GmbH</name>
      <address>
        <city>Berlin</city>
        <zip>14165</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Essen; Innere Klinik und Poliklinik für Tumorforschung</name>
      <address>
        <city>Essen</city>
        <zip>45122</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Thoraxklinik Heidelberg gGmbH</name>
      <address>
        <city>Heidelberg</city>
        <zip>69126</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum der Universität München</name>
      <address>
        <city>Muenchen</city>
        <zip>80336</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pius-Hospital; Klinik fuer Haematologie und Onkologie</name>
      <address>
        <city>Oldenburg</city>
        <zip>26121</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Chinese University of Hong Kong</name>
      <address>
        <city>Shatin</city>
        <zip>123456</zip>
        <country>Hong Kong</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Santa Maria Delle Croci</name>
      <address>
        <city>Ravenna</city>
        <state>Emilia-Romagna</state>
        <zip>48100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Nazionale Tumori Regina Elena</name>
      <address>
        <city>Roma</city>
        <state>Lazio</state>
        <zip>00144</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IEO; Divisione di Sviluppo di Nuovi Farmaci per Terapie Innovative</name>
      <address>
        <city>Milano</city>
        <state>Lombardia</state>
        <zip>20141</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asst Grande Ospedale Metropolitano Niguarda</name>
      <address>
        <city>Milano</city>
        <state>Lombardia</state>
        <zip>20162</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>03080</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asan Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>05505</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samsung Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>06351</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Severance Hospital, Yonsei University Health System; Oncology</name>
      <address>
        <city>Seoul</city>
        <zip>120-752</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Antoni van Leeuwenhoek Ziekenhuis</name>
      <address>
        <city>Amsterdam</city>
        <zip>1066 CX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitair Medisch Centrum Groningen</name>
      <address>
        <city>Groningen</city>
        <zip>9713 GZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Centre</name>
      <address>
        <city>Singapore</city>
        <zip>169610</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Catala d Oncologia Hospitalet</name>
      <address>
        <city>Hospitalet de Llobregat</city>
        <state>Barcelona</state>
        <zip>08908</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vall d?Hebron Institute of Oncology (VHIO), Barcelona</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinic de Barcelona</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Ramon y Cajal; Servicio de Oncologia</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario 12 de Octubre; Servicio de Oncologia</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taipei Veterans General Hospital</name>
      <address>
        <city>Taipei City</city>
        <zip>11217</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>10002</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Guys and St Thomas NHS Foundation Trust, Guys Hospital</name>
      <address>
        <city>London</city>
        <zip>SE1 9RT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute</name>
      <address>
        <city>London</city>
        <zip>W1G 6AD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University College London Hospitals NHS Foundation Trust; NIHR UCLH Clinical Research Facility</name>
      <address>
        <city>London</city>
        <zip>W1T 7HA</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Christie NHS Foundation Trust</name>
      <address>
        <city>Manchester</city>
        <zip>M20 4BX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>China</country>
    <country>France</country>
    <country>Germany</country>
    <country>Hong Kong</country>
    <country>Italy</country>
    <country>Korea, Republic of</country>
    <country>Netherlands</country>
    <country>Singapore</country>
    <country>Spain</country>
    <country>Taiwan</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.ret-arrowtrial.com/</url>
    <description>More information about the study</description>
  </link>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>January 20, 2017</study_first_submitted>
  <study_first_submitted_qc>January 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 31, 2017</study_first_posted>
  <last_update_submitted>August 25, 2023</last_update_submitted>
  <last_update_submitted_qc>August 25, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 28, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>RET Lung</keyword>
  <keyword>RET Thyroid</keyword>
  <keyword>RET fusion</keyword>
  <keyword>RET alteration</keyword>
  <keyword>RET mutation</keyword>
  <keyword>RET positive</keyword>
  <keyword>RET inhibitor</keyword>
  <keyword>RET altered</keyword>
  <keyword>RET rearrangement</keyword>
  <keyword>RET NSCLC</keyword>
  <keyword>RET medullary thyroid cancer</keyword>
  <keyword>RET-rearranged NSCLC</keyword>
  <keyword>RET-rearranged thyroid</keyword>
  <keyword>M918T</keyword>
  <keyword>TRIM33-RET</keyword>
  <keyword>RET fusion lung cancer</keyword>
  <keyword>RET fusion thyroid cancer</keyword>
  <keyword>lung cancer mutation</keyword>
  <keyword>BLU 667</keyword>
  <keyword>RET tyrosine kinase</keyword>
  <keyword>RET gene mutation</keyword>
  <keyword>RET kinase</keyword>
  <keyword>RET MTC</keyword>
  <keyword>advanced lung cancer</keyword>
  <keyword>advanced non small cell lung cancer</keyword>
  <keyword>metastatic lung cancer</keyword>
  <keyword>KIF5B-RET</keyword>
  <keyword>CCDC6-RET</keyword>
  <keyword>NCOA4-RET</keyword>
  <keyword>advance solid tumor</keyword>
  <keyword>V804L</keyword>
  <keyword>V804M</keyword>
  <keyword>thyroid cancer RET inhibitor</keyword>
  <keyword>lung cancer RET inhibitor</keyword>
  <keyword>RET PTC</keyword>
  <keyword>rearranged during transfection</keyword>
  <keyword>RET-PTC1</keyword>
  <keyword>RET-PTC</keyword>
  <keyword>RET-PTC3</keyword>
  <keyword>RET-PTC4</keyword>
  <keyword>PRKAR1A-RET</keyword>
  <keyword>RET-PTC2</keyword>
  <keyword>GOLGA5-RET</keyword>
  <keyword>RET-PTC5</keyword>
  <keyword>ERC1-RET</keyword>
  <keyword>KTN1-RET</keyword>
  <keyword>RET-PTC8</keyword>
  <keyword>HOOK3-RET</keyword>
  <keyword>PCM1-RET</keyword>
  <keyword>TRIM24-RET</keyword>
  <keyword>RET-PTC6</keyword>
  <keyword>TRIM27-RET</keyword>
  <keyword>RET-PTC7</keyword>
  <keyword>AKAP13-RET</keyword>
  <keyword>FKBP15-RET</keyword>
  <keyword>SPECC1L-RET</keyword>
  <keyword>TBL1XR1-RET</keyword>
  <keyword>BCR-RET</keyword>
  <keyword>FGRF1OP-RET</keyword>
  <keyword>RFG8-RET</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
    <mesh_term>Adenocarcinoma</mesh_term>
    <mesh_term>Colonic Neoplasms</mesh_term>
    <mesh_term>Thyroid Neoplasms</mesh_term>
    <mesh_term>Neuroendocrine Tumors</mesh_term>
    <mesh_term>Colorectal Neoplasms</mesh_term>
    <mesh_term>Neuroectodermal Tumors</mesh_term>
    <mesh_term>Neuroectodermal Tumors, Primitive</mesh_term>
    <mesh_term>Head and Neck Neoplasms</mesh_term>
    <mesh_term>Gastrointestinal Neoplasms</mesh_term>
    <mesh_term>Digestive System Neoplasms</mesh_term>
    <mesh_term>Neoplasms by Site</mesh_term>
    <mesh_term>Thyroid Cancer, Papillary</mesh_term>
    <mesh_term>Carcinoma, Neuroendocrine</mesh_term>
    <mesh_term>Neoplasms by Histologic Type</mesh_term>
    <mesh_term>Thoracic Neoplasms</mesh_term>
    <mesh_term>Intestinal Neoplasms</mesh_term>
    <mesh_term>Neoplasms, Glandular and Epithelial</mesh_term>
    <mesh_term>Respiratory Tract Neoplasms</mesh_term>
    <mesh_term>Bronchial Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Bronchogenic</mesh_term>
    <mesh_term>Endocrine Gland Neoplasms</mesh_term>
    <mesh_term>Neoplasms, Germ Cell and Embryonal</mesh_term>
    <mesh_term>Neoplasms, Nerve Tissue</mesh_term>
    <mesh_term>Adenocarcinoma, Papillary</mesh_term>
    <mesh_term>Gastrointestinal Diseases</mesh_term>
    <mesh_term>Digestive System Diseases</mesh_term>
    <mesh_term>Colonic Diseases</mesh_term>
    <mesh_term>Intestinal Diseases</mesh_term>
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Respiratory Tract Diseases</mesh_term>
    <mesh_term>Thyroid Diseases</mesh_term>
    <mesh_term>Endocrine System Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pralsetinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03037385
org study id: BO42863
secondary id: 2016-004390-41
secondary id: BLU-667-1101
nct id: NCT03037385
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase 1/2, open-label, first-in-human (FIH) study designed to evaluate the safety,
      tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antineoplastic
      activity of pralsetinib (BLU-667) administered orally in participants with medullary thyroid
      cancer (MTC), RET-altered NSCLC and other RET-altered solid tumors.
The study consists of 2 parts, a dose-escalation part (Phase 1) and an expansion part (Phase
      2). Both parts will enroll participants with advanced non-resectable NSCLC, advanced
      non-resectable thyroid cancer and other advanced solid tumors that have progressed following
      standard systemic therapy, have not adequately responded to standard systemic therapy, or the
      participants must be intolerant to or the Investigator has determined that treatment with
      standard therapy is not appropriate, or there must be no accepted standard therapy for their
      disease.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: Phase 1 (Complete):
Advanced MTC, NSCLC or other solid tumor
30-600mg (PO QD or BID)
Phase 2 (400mg QD):
Group 1: RET fusion NSCLC previously treated with a platinum chemotherapy
Group 2: RET fusion NSCLC not previously treated for metastatic disease
Group 3: MTC previously treated with cabozantinib and/or vandetanib
Group 4: MTC not previously treated with cabozantinib or vandetanib
Group 5: Other solid tumors with a RET fusion not eligible for any of the other groups and previously treated with SOC or have no acceptable SOC for their tumor type as determined by the investigator
Group 6: Any solid tumor with a RET alteration (fusion or mutation) previously treated with a selective RET Inhibitor
Group 7: Other solid tumors with a RET mutation previously treated with SOC
Group 8: RET fusion NSCLC previously treated with a platinum chemotherapy (China only)
Group 9: MTC not previously treated with systemic therapy for advanced or metastatic disease (China only)
primary purpose: Treatment
masking: None (Open Label)
measure: (Phase 1) Determination of Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Pralsetinib
time frame: Cycle 1 (28 days) of treatment for MTD and at the end of every cycle (28 days) for RP2D for approximately 12 months or earlier if participant terminates from the study
measure: (Phase 1) Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
time frame: Every cycle (28 days) for approximately 12 months or earlier if participant terminates from the study, and 30 days after the last dose
measure: (Phase 2) Overall Response Rate (ORR)
time frame: Approximately every 8 weeks or 16 weeks based on the treatment cycle
description: As assessed by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) or Response Assessment in Neuro-Oncology (RANO), as appropriate per tumor type
measure: (Phase 2) Number of Participants with AEs and SAEs
time frame: Every cycle (28 days) for approximately 24 months or earlier if participant terminates from the study, and 30 days after the last dose
measure: (Phase 1) ORR
time frame: Approximately every 8 weeks during treatment, 14 days after the last dose, and every 3 months after the last dose (Up to 12 months) in participants without progressive disease
description: As assessed by RECIST v1.1 or RANO, as appropriate per tumor type
measure: (Phase 1) RET Gene Status and Correlation Between RET Gene Status and ORR, CBR, DOR, DCR, PFS and Other Antineoplastic Measures
time frame: Approximately every 8 weeks or 16 weeks based on the treatment cycle (Up to approximately 12 months)
description: Clinical Benefit Rate (CBR), Duration of Response (DOR), Disease Control Rate (DCR), Progression Free Survival (PFS)
measure: (Phase 2) CBR
time frame: Approximately every 8 weeks or 16 weeks based on the treatment cycle
measure: (Phase 2) DOR
time frame: Approximately every 8 weeks or 16 weeks based on the treatment cycle
measure: (Phase 2) DCR
time frame: Approximately every 8 weeks or 16 weeks based on the treatment cycle
measure: (Phase 2) PFS
time frame: Approximately every 8 weeks or 16 weeks based on the treatment cycle (Up to approximately 84 months)
measure: (Phase 2) Overall Survival (OS)
time frame: Approximately every 8 weeks or 16 weeks based on the treatment cycle (Up to approximately 84 months)
measure: (Phase 2) RET Gene Status and Correlation Between RET Gene Status and ORR, CBR, DOR, DCR and Other Antineoplastic Measures
time frame: On Day 1 of Cycle 1 (each cycle is of 28 days), 2 and 3 and every other cycle thereafter up to Cycle 13
description: RET gene status (i.e. gene fusion partner or primary mutation and, for MTC, whether hereditary or sporadic)
measure: (Phases 1 and 2) Pharmacokinetic Parameters Including Maximum Plasma Drug Concentration (Cmax)
time frame: Approximately every 2 weeks in Cycle 1 and monthly through Cycle 4
measure: (Phases 1 and 2) Pharmacokinetic Parameters Including Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours Postdose (AUC0-24)
time frame: Approximately every 2 weeks in Cycle 1 and monthly through Cycle 4
measure: (Phases 1 and 2) Pharmacokinetic Parameters Including Terminal Elimination Half-life (t1/2)
time frame: Approximately every 2 weeks in Cycle 1 and monthly through Cycle 4
measure: (Phase 2) Electrocardiogram (ECG) Assessment Using QT Analysis
time frame: Effects of BLU-667 on ECG parameters on Cycle 1 Day 1 and Cycle 1 Day 15
description: Will be measured from lead II and will be corrected for heart rate (QTc)n using Fridericia's correction factors
measure: (Phases 1 and 2) Pharmacodynamic Parameters Including Changes in Blood Calcitonin
time frame: Approximately every 2 weeks in Cycle 1 and monthly through Cycle 3 and every other month through Cycle 13
description: MTC participants only
measure: (Phases 1 and 2) Pharmacodynamic Parameters Including Tumor Marker, Carcinoembryonic Antigen (CEA)
time frame: Approximately every 2 weeks in Cycle 1 and monthly through Cycle 3 and every other month through Cycle 13
description: MTC participants only
measure: (Phase 2) Assess Intracranial Response Rate and Time to Intracranial Progression in Participants With NSCLC
time frame: Approximately every 8 weeks or 16 weeks based on the treatment cycle
description: Target by RECIST v1.1 or RANO
arm group label: Phase 1 Dose Escalation
arm group type: Experimental
description: Multiple doses of pralsetinib (BLU-667) for oral administration.
arm group label: Phase 2 Dose Expansion
arm group type: Experimental
description: Oral dose of pralsetinib (BLU-667) as determined during Dose Escalation.
intervention type: Drug
intervention name: pralsetinib (BLU-667)
description: pralsetinib (BLU-667) is a potent and selective inhibitor of the RET mutations, fusions, and predicted resistant mutants
arm group label: Phase 1 Dose Escalation
arm group label: Phase 2 Dose Expansion
other name: BLU-667
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
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country: Belgium
country: China
country: France
country: Germany
country: Hong Kong
country: Italy
country: Korea, Republic of
country: Netherlands
country: Singapore
country: Spain
country: Taiwan
country: United Kingdom
country: United States
url: http://www.ret-arrowtrial.com/
description: More information about the study
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Neoplasms
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Adenocarcinoma
mesh term: Colonic Neoplasms
mesh term: Thyroid Neoplasms
mesh term: Neuroendocrine Tumors
mesh term: Colorectal Neoplasms
mesh term: Neuroectodermal Tumors
mesh term: Neuroectodermal Tumors, Primitive
mesh term: Head and Neck Neoplasms
mesh term: Gastrointestinal Neoplasms
mesh term: Digestive System Neoplasms
mesh term: Neoplasms by Site
mesh term: Thyroid Cancer, Papillary
mesh term: Carcinoma, Neuroendocrine
mesh term: Neoplasms by Histologic Type
mesh term: Thoracic Neoplasms
mesh term: Intestinal Neoplasms
mesh term: Neoplasms, Glandular and Epithelial
mesh term: Respiratory Tract Neoplasms
mesh term: Bronchial Neoplasms
mesh term: Carcinoma, Bronchogenic
mesh term: Endocrine Gland Neoplasms
mesh term: Neoplasms, Germ Cell and Embryonal
mesh term: Neoplasms, Nerve Tissue
mesh term: Adenocarcinoma, Papillary
mesh term: Gastrointestinal Diseases
mesh term: Digestive System Diseases
mesh term: Colonic Diseases
mesh term: Intestinal Diseases
mesh term: Lung Diseases
mesh term: Respiratory Tract Diseases
mesh term: Thyroid Diseases
mesh term: Endocrine System Diseases
mesh term: Pralsetinib
sharing ipd: No