<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/NCT03000257</url>
  </required_header>
  <id_info>
    <org_study_id>M15-891</org_study_id>
    <secondary_id>2016-002520-89</secondary_id>
    <nct_id>NCT03000257</nct_id>
  </id_info>
  <brief_title>A Study of Budigalimab (ABBV-181) in Participants With Advanced Solid Tumors</brief_title>
  <official_title>A Multicenter, Phase 1, Open-Label, Dose-Escalation Study of ABBV-181 as Monotherapy and in Combination With Another Anti-Cancer Therapy in Subjects With Advanced Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AbbVie</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AbbVie</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open-label, Phase I, dose-escalation study to determine the recommended Phase 2&#xD;
      dose (RPTD), maximum tolerated dose (MTD), and evaluate the safety and pharmacokinetic (PK)&#xD;
      profile of budigalimab. This study will also evaluate the safety and tolerability of&#xD;
      budigalimab in combination with Rovalpituzumab Tesirine and budigalimab in combination with&#xD;
      venetoclax. The study will consist of 3 parts: budigalimab monotherapy dose escalation and&#xD;
      expansion, budigalimab in combination with Rovalpituzumab Tesirine and budigalimab in&#xD;
      combination with venetoclax.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 14, 2016</start_date>
  <completion_date type="Actual">March 29, 2022</completion_date>
  <primary_completion_date type="Actual">March 29, 2022</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>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Part 1: Recommended Phase 2 Dose (RPTD) for Budigalimab</measure>
    <time_frame>Up to 6 months</time_frame>
    <description>If a maximum tolerated dose (MTD) is reached, the RPTD of budigalimab will not be a dose higher than the defined MTD, and will be selected based on the type(s) and occurrence(s) of dose limiting toxicities which occur in addition to the MTD. If a MTD is not reached, then the RPTD will be defined based on the safety and other available data.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1: Maximum tolerated dose (MTD) of Budigalimab</measure>
    <time_frame>Up to 6 months</time_frame>
    <description>MTD will be defined at the highest dose level at which less than 2 of 6 subjects or less than 33% of (if cohort is expanded beyond 6) participants experience a dose limiting toxicity.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1 and Part 3: Terminal Half-life (t1/2) of Budigalimab</measure>
    <time_frame>Up to 4 Weeks</time_frame>
    <description>Terminal phase elimination half-life (t1/2) of Budigalimab</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1 and Part 3: Maximum Observed Serum Concentration (Cmax) of Budigalimab</measure>
    <time_frame>Up to 12 Weeks</time_frame>
    <description>Maximum Serum Concentration (Cmax) of Budigalimab</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1 and Part 3: Time to Cmax (Tmax) of Budigalimab</measure>
    <time_frame>Up to 12 Weeks</time_frame>
    <description>Time to maximum plasma concentration of Budigalimab</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1 and Part 3: Area Under the Serum Concentration Time Curve from Time 0 to Last Measurable Concentration (AUCt) of Budigalimab</measure>
    <time_frame>Up to 12 Weeks</time_frame>
    <description>Area Under the Plasma Concentration-time Curve from time 0 to last measurable concentration (AUCt) of Budigalimab</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2: Recommended Phase 2 Dose (RPTD) and Schedule for Budigalimab and Rovalpituzumab Tesirine Combination</measure>
    <time_frame>Up to 6 Months</time_frame>
    <description>The safety and tolerability of a single dose of Budigalimab in combination with Rovalpituzumab Tesirine will be assessed in patients with advanced small cell lung cancer (SCLC) to determine the RPTD and schedule for the combination.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 3: Recommended Phase 2 Dose (RPTD) and Schedule for Budigalimab and Venetoclax Combination.</measure>
    <time_frame>Up to 6 Months</time_frame>
    <description>The safety and tolerability of Budigalimab in combination with venetoclax will be assessed in patients with metastatic Non-Small Cell Lung Cancer (NSCLC) to determine the RPTD for the combination.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 3: Maximum Observed Serum Concentration (Cmax) for Venetoclax</measure>
    <time_frame>Up to 12 Weeks</time_frame>
    <description>Maximum Serum Concentration (Cmax) for Venetoclax</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 3: Area Under the Serum Concentration Time Curve from Time 0 to 24 Hours Post-dose (AUC(0-24)) of Venetoclax</measure>
    <time_frame>Up to 12 Weeks</time_frame>
    <description>Area Under the Plasma Concentration-time Curve from time 0 to time 0 to 24 hours post-dose (AUC(0-24)) of Venetoclax</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 3: Time to Cmax (Tmax) of Venetoclax</measure>
    <time_frame>Up to 12 Weeks</time_frame>
    <description>Time to maximum plasma concentration of of Venetoclax</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1, Part 2, Part 3: Number of Participants with Adverse Events</measure>
    <time_frame>From first dose of study drug until 90 days following last dose of study drug (up to 24 months)</time_frame>
    <description>An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Part 2: Terminal Half-life (t1/2) of Budigalimab</measure>
    <time_frame>Up to 4 Weeks</time_frame>
    <description>Terminal phase elimination half-life (t1/2) of Budigalimab</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: Terminal Half-life (t1/2) of Rovalpituzumab Tesirine</measure>
    <time_frame>Up to 4 Weeks</time_frame>
    <description>Terminal phase elimination half-life (t1/2) of Rovalpituzumab Tesirine</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: Maximum Observed Serum Concentration (Cmax) of Rovalpituzumab Tesirine</measure>
    <time_frame>Up to 12 Weeks</time_frame>
    <description>Maximum Serum Concentration (Cmax) of Rovalpituzumab Tesirine</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: Area Under the Serum Concentration Time Curve from Time 0 to Last Measurable Concentration (AUCt) of Rovalpituzumab Tesirine</measure>
    <time_frame>Up to 12 Weeks</time_frame>
    <description>Area Under the Plasma Concentration-time Curve from time 0 to last measurable concentration (AUCt) of Rovalpituzumab Tesirine</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: Area Under the Serum Concentration Time Curve from Time 0 to Last Measurable Concentration (AUCt) of Budigalimab</measure>
    <time_frame>Up to 12 Weeks</time_frame>
    <description>Area Under the Plasma Concentration-time Curve from time 0 to last measurable concentration (AUCt) of Budigalimab</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: Time to Cmax (Tmax) of Budigalimab</measure>
    <time_frame>Up to 12 Weeks</time_frame>
    <description>Time to maximum plasma concentration of Budigalimab</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: Time to Cmax (Tmax) of Rovalpituzumab Tesirine</measure>
    <time_frame>Up to 12 Weeks</time_frame>
    <description>Time to maximum plasma concentration of Rovalpituzumab Tesirine</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1 and Part 3: Objective response rate (ORR)</measure>
    <time_frame>First dose of study drug through at least 30 days after last dose of study drug.</time_frame>
    <description>ORR is defined as the proportion of subjects with a confirmed partial or complete response to the treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1 and Part 3: Clinical benefit rate (CBR, defined as CR, PR or SD)</measure>
    <time_frame>First dose of study drug through at least 30 days after last dose of study drug.</time_frame>
    <description>CBR defined as the proportion of subjects with a confirmed partial response (PR), complete response (CR), or stable disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1 and Part 3: Progression-free survival (PFS)</measure>
    <time_frame>First dose of study drug through at least 30 days after last dose of study drug.</time_frame>
    <description>PFS time is defined as the time from the participant's first dose of study drug (Day 1) to either the participant's disease progression or death, whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1, Part 2 and Part 3: Duration of objective response (DOR)</measure>
    <time_frame>First dose of study drug through at least 30 days after last dose of study drug.</time_frame>
    <description>DOR for a participant is defined as the time from the participant's initial objective response to study drug therapy to disease progression or death, whichever occurs first.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">182</enrollment>
  <condition>Advanced Solid Tumors</condition>
  <arm_group>
    <arm_group_label>ABBV-181 plus Venetoclax</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Venetoclax will be taken once daily beginning 7 days prior to cycle 1 and continuing daily for a 28 day cycle and ABBV-181 will be administered every 4 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ABBV-181</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ABBV-181 will be administered at escalating dose levels in 28-day dosing cycles (2 doses per cycle). Based on available safety, pharmacokinetic, and pharmacodynamic data from the dose-escalation part of the study, participants will be enrolled in dose-expansion cohorts to further evaluate ABBV-181 at a dose level which is at or below the Maximum tolerated dose (MTD). In the Monotherapy Expansion portion of the study, ABBV-181 will be administered in 28-day dosing cycles at either 1 dose per cycle or 2 doses per cycle. Based on available safety, PK and PD data from the single agent dose-escalation part of the study, a dose for ABBV-181 will be selected to evaluate in combination with Rovalpituzumab Tesirine or venetoclax.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ABBV-181 plus Rovalpituzumab Tesirine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Rovalpituzumab Tesirine will be given once every six weeks times two doses and ABBV-181 will be administered every 3 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Venetoclax</intervention_name>
    <description>Tablet taken orally</description>
    <arm_group_label>ABBV-181 plus Venetoclax</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rovalpituzumab Tesirine</intervention_name>
    <description>Intravenous infusion</description>
    <arm_group_label>ABBV-181 plus Rovalpituzumab Tesirine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ABBV-181</intervention_name>
    <description>Intravenous infusion</description>
    <arm_group_label>ABBV-181</arm_group_label>
    <arm_group_label>ABBV-181 plus Rovalpituzumab Tesirine</arm_group_label>
    <arm_group_label>ABBV-181 plus Venetoclax</arm_group_label>
    <other_name>Budigalimab</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participant must have an advanced solid tumor and must not be a candidate for surgical&#xD;
             resection or other approved therapeutic regimen known to provide clinical benefit. For&#xD;
             dose escalation, the participant may have been previously treated with a programmed&#xD;
             cell death 1 (PD-I) targeting agent. For dose expansion, the participant must be&#xD;
             PD-I/PD-L1 targeting agent naïve. For Part 2 budigalimab in combination with&#xD;
             rovalpituzumab tesirine, the participant must have SCLC with progressive disease and&#xD;
             have failed platinum containing therapy and be PD-1/PD-L1 targeting agent naïve. For&#xD;
             Part 3 budigalimab in combination with venetoclax, the participant must have locally&#xD;
             advanced or metastatic NSCLC and received 1 to 4 prior lines of therapy in the&#xD;
             advanced or metastatic setting including 1 regimen that included a PD-1 or PD-L1&#xD;
             targeting agent which was discontinued following disease progression. Participants who&#xD;
             are naïve to treatment with a PD-1/PD-L1 targeting agent OR who have received more&#xD;
             than 1 regimen containing a PD-1/PD-L1 targeting agent are NOT eligible for Part 3.&#xD;
&#xD;
          -  Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0&#xD;
             to 2 for the monotherapy cohort and an ECOG 0 to 1 for budigalimab in combination with&#xD;
             rovalpituzumab tesirine cohort (Part 2) and budigalimab in combination with venetoclax&#xD;
             (Part 3).&#xD;
&#xD;
          -  Participants have adequate bone marrow, renal, hepatic and coagulation function.&#xD;
&#xD;
          -  Participants must have measurable or evaluable disease per Response Evaluation&#xD;
             Criteria in Solid Tumors (RECIST) version 1.1 in the dose escalation portion of the&#xD;
             trial. Participants in the expansion cohort must have measurable disease per RECIST&#xD;
             version 1.1 or disease evaluable by assessment of tumor antigens. Participants&#xD;
             enrolled in budigalimab in combination with venetoclax cohort (Part 3) must have&#xD;
             measurable disease per RECIST version 1.1.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participant has received anticancer therapy including chemotherapy, immunotherapy,&#xD;
             radiation therapy, biologic, small molecule, herbal therapy, or any investigational&#xD;
             therapy within a period of 5 half-lives, prior to the first dose of budigalimab or&#xD;
             Rovalpituzumab Tesirine or venetoclax.&#xD;
&#xD;
          -  For budigalimab in combination with rovalpituzumab tesirine cohort (Part 2),&#xD;
             participant must not have had prior exposure to Rovalpituzumab Tesirine or a&#xD;
             pyrrolobenzodiazepine (PBD) based drug.&#xD;
&#xD;
          -  Participant has unresolved adverse events greater than grade 1 from prior anticancer&#xD;
             therapy except for alopecia.&#xD;
&#xD;
          -  Current or prior use of immunosuppressive medication within 14 days prior to the first&#xD;
             dose (with certain exceptions).&#xD;
&#xD;
          -  History of primary immunodeficiency, bone marrow transplantation, chronic lymphocytic&#xD;
             leukemia, solid organ transplantation, or previous clinical diagnosis of tuberculosis.&#xD;
&#xD;
          -  Confirmed positive test results for human immunodeficiency virus (HIV), or&#xD;
             participants with chronic or active hepatitis A, B or C. Participants who have a&#xD;
             history of hepatitis B or C who have undetectable hepatitis B (HBV) DNA or hepatitis C&#xD;
             (HCV) RNA after anti-viral therapy may be enrolled.&#xD;
&#xD;
          -  Participant has known history or inflammatory bowel disease, pneumonitis, or known&#xD;
             uncontrolled metastases to the central nervous system (CNS) (with certain exceptions).&#xD;
&#xD;
          -  Participants with a history of or ongoing pneumonitis or interstitial lung disease are&#xD;
             also excluded.&#xD;
&#xD;
          -  For budigalimab plus venetoclax therapy (Part 3), participant must not receive a&#xD;
             strong or moderate inducer or inhibitor of cytochrome P450 (CYP)3A within 7 days&#xD;
             before first venetoclax dose.&#xD;
&#xD;
          -  For budigalimab plus venetoclax therapy (Part 3), participants with a known&#xD;
             gastrointestinal disorder (i.e.: malabsorption syndrome), complication (i.e.:&#xD;
             dysphagia) or surgery that could make consumption or absorption of oral medication&#xD;
             problematic are also excluded.&#xD;
&#xD;
          -  All Cohorts: Participants with a history of Stevens-Johnson syndrome (SJS), Toxic&#xD;
             epidermal necrolysis (TEN), or drug reaction with eosinophilia and systemic symptoms&#xD;
             (DRESS)&#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>ABBVIE INC.</last_name>
    <role>Study Director</role>
    <affiliation>AbbVie</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Moores Cancer Center at UC San Diego /ID# 157374</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Chicago Medical Center /ID# 157375</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637-1443</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carolina BioOncology Institute /ID# 157376</name>
      <address>
        <city>Huntersville</city>
        <state>North Carolina</state>
        <zip>28078</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>South Texas Accelerated Research Therapeutics /ID# 157378</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Cancer Specialists - Fairfax /ID# 157377</name>
      <address>
        <city>Fairfax</city>
        <state>Virginia</state>
        <zip>22031</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Blacktown Hospital /ID# 167386</name>
      <address>
        <city>Blacktown</city>
        <state>New South Wales</state>
        <zip>2148</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Vincent's Hospital Melbourne /ID# 167552</name>
      <address>
        <city>Fitzroy Melbourne</city>
        <state>Victoria</state>
        <zip>3065</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Linear Clinical Research /ID# 170797</name>
      <address>
        <city>Nedlands</city>
        <state>Western Australia</state>
        <zip>6000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medizinische Universitaet Graz /ID# 168752</name>
      <address>
        <city>Graz</city>
        <state>Steiermark</state>
        <zip>8036</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitair Ziekenhuis Antwerpen /ID# 170702</name>
      <address>
        <city>Edegem</city>
        <state>Antwerpen</state>
        <zip>2650</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Gent /ID# 170881</name>
      <address>
        <city>Gent</city>
        <state>Oost-Vlaanderen</state>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cross Cancer Institute /ID# 167603</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G 1Z2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tampere University Hospital /ID# 166839</name>
      <address>
        <city>Tampere</city>
        <state>Pirkanmaa</state>
        <zip>33520</zip>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Docrates Cancer Center /ID# 166838</name>
      <address>
        <city>Helsinki</city>
        <zip>00180</zip>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Bergonie /ID# 162662</name>
      <address>
        <city>Bordeaux</city>
        <state>Gironde</state>
        <zip>33000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut du Cancer de Montpellier - Val d'Aurelle /ID# 163999</name>
      <address>
        <city>Montpellier CEDEX 5</city>
        <state>Herault</state>
        <zip>34298</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Leon Berard /ID# 162660</name>
      <address>
        <city>Lyon CEDEX 08</city>
        <state>Rhone</state>
        <zip>69373</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Gustave Roussy /ID# 162753</name>
      <address>
        <city>Villejuif Cedex</city>
        <state>Val-de-Marne</state>
        <zip>94805</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Center Hospital East /ID# 166433</name>
      <address>
        <city>Kashiwa-shi</city>
        <state>Chiba</state>
        <zip>277-8577</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Hospital Organization Kyushu Cancer Center /ID# 206229</name>
      <address>
        <city>Fukuoka-shi</city>
        <state>Fukuoka</state>
        <zip>811-1395</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Center Hospital /ID# 166279</name>
      <address>
        <city>Chuo-ku</city>
        <state>Tokyo</state>
        <zip>104-0045</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Fundacion Jimenez Diaz /ID# 163862</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario HM Sanchinarro /ID# 163861</name>
      <address>
        <city>Madrid</city>
        <zip>28050</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinico Universitario de Valencia /ID# 163925</name>
      <address>
        <city>Valencia</city>
        <zip>46010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Taiwan University Hospital /ID# 163997</name>
      <address>
        <city>Taipei City</city>
        <zip>100</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taipei Medical University Hospital /ID# 163998</name>
      <address>
        <city>Taipei City</city>
        <zip>11031</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Austria</country>
    <country>Belgium</country>
    <country>Canada</country>
    <country>Finland</country>
    <country>France</country>
    <country>Japan</country>
    <country>Spain</country>
    <country>Taiwan</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Italy</country>
  </removed_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>December 15, 2016</study_first_submitted>
  <study_first_submitted_qc>December 19, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 22, 2016</study_first_posted>
  <last_update_submitted>April 13, 2022</last_update_submitted>
  <last_update_submitted_qc>April 13, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Budigalimab</keyword>
  <keyword>Cancer</keyword>
  <keyword>Advanced Solid Tumors</keyword>
  <keyword>Non-small cell lung cancer (NSCLC)</keyword>
  <keyword>Triple negative breast cancer</keyword>
  <keyword>Ovarian cancer</keyword>
  <keyword>Hepatocellular carcinoma</keyword>
  <keyword>Gastric cancer</keyword>
  <keyword>Small cell lung cancer</keyword>
  <keyword>Mesothelioma</keyword>
  <keyword>Cholangiocarcinoma</keyword>
  <keyword>Merkel cell carcinoma</keyword>
  <keyword>Head and neck cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Venetoclax</mesh_term>
    <mesh_term>Rovalpituzumab tesirine</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/NCT03000257
org study id: M15-891
secondary id: 2016-002520-89
nct id: NCT03000257
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This is an open-label, Phase I, dose-escalation study to determine the recommended Phase 2
      dose (RPTD), maximum tolerated dose (MTD), and evaluate the safety and pharmacokinetic (PK)
      profile of budigalimab. This study will also evaluate the safety and tolerability of
      budigalimab in combination with Rovalpituzumab Tesirine and budigalimab in combination with
      venetoclax. The study will consist of 3 parts: budigalimab monotherapy dose escalation and
      expansion, budigalimab in combination with Rovalpituzumab Tesirine and budigalimab in
      combination with venetoclax.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Part 1: Recommended Phase 2 Dose (RPTD) for Budigalimab
time frame: Up to 6 months
description: If a maximum tolerated dose (MTD) is reached, the RPTD of budigalimab will not be a dose higher than the defined MTD, and will be selected based on the type(s) and occurrence(s) of dose limiting toxicities which occur in addition to the MTD. If a MTD is not reached, then the RPTD will be defined based on the safety and other available data.
measure: Part 1: Maximum tolerated dose (MTD) of Budigalimab
time frame: Up to 6 months
description: MTD will be defined at the highest dose level at which less than 2 of 6 subjects or less than 33% of (if cohort is expanded beyond 6) participants experience a dose limiting toxicity.
measure: Part 1 and Part 3: Terminal Half-life (t1/2) of Budigalimab
time frame: Up to 4 Weeks
description: Terminal phase elimination half-life (t1/2) of Budigalimab
measure: Part 1 and Part 3: Maximum Observed Serum Concentration (Cmax) of Budigalimab
time frame: Up to 12 Weeks
description: Maximum Serum Concentration (Cmax) of Budigalimab
measure: Part 1 and Part 3: Time to Cmax (Tmax) of Budigalimab
time frame: Up to 12 Weeks
description: Time to maximum plasma concentration of Budigalimab
measure: Part 1 and Part 3: Area Under the Serum Concentration Time Curve from Time 0 to Last Measurable Concentration (AUCt) of Budigalimab
time frame: Up to 12 Weeks
description: Area Under the Plasma Concentration-time Curve from time 0 to last measurable concentration (AUCt) of Budigalimab
measure: Part 2: Recommended Phase 2 Dose (RPTD) and Schedule for Budigalimab and Rovalpituzumab Tesirine Combination
time frame: Up to 6 Months
description: The safety and tolerability of a single dose of Budigalimab in combination with Rovalpituzumab Tesirine will be assessed in patients with advanced small cell lung cancer (SCLC) to determine the RPTD and schedule for the combination.
measure: Part 3: Recommended Phase 2 Dose (RPTD) and Schedule for Budigalimab and Venetoclax Combination.
time frame: Up to 6 Months
description: The safety and tolerability of Budigalimab in combination with venetoclax will be assessed in patients with metastatic Non-Small Cell Lung Cancer (NSCLC) to determine the RPTD for the combination.
measure: Part 3: Maximum Observed Serum Concentration (Cmax) for Venetoclax
time frame: Up to 12 Weeks
description: Maximum Serum Concentration (Cmax) for Venetoclax
measure: Part 3: Area Under the Serum Concentration Time Curve from Time 0 to 24 Hours Post-dose (AUC(0-24)) of Venetoclax
time frame: Up to 12 Weeks
description: Area Under the Plasma Concentration-time Curve from time 0 to time 0 to 24 hours post-dose (AUC(0-24)) of Venetoclax
measure: Part 3: Time to Cmax (Tmax) of Venetoclax
time frame: Up to 12 Weeks
description: Time to maximum plasma concentration of of Venetoclax
measure: Part 1, Part 2, Part 3: Number of Participants with Adverse Events
time frame: From first dose of study drug until 90 days following last dose of study drug (up to 24 months)
description: An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
measure: Part 2: Terminal Half-life (t1/2) of Budigalimab
time frame: Up to 4 Weeks
description: Terminal phase elimination half-life (t1/2) of Budigalimab
measure: Part 2: Terminal Half-life (t1/2) of Rovalpituzumab Tesirine
time frame: Up to 4 Weeks
description: Terminal phase elimination half-life (t1/2) of Rovalpituzumab Tesirine
measure: Part 2: Maximum Observed Serum Concentration (Cmax) of Rovalpituzumab Tesirine
time frame: Up to 12 Weeks
description: Maximum Serum Concentration (Cmax) of Rovalpituzumab Tesirine
measure: Part 2: Area Under the Serum Concentration Time Curve from Time 0 to Last Measurable Concentration (AUCt) of Rovalpituzumab Tesirine
time frame: Up to 12 Weeks
description: Area Under the Plasma Concentration-time Curve from time 0 to last measurable concentration (AUCt) of Rovalpituzumab Tesirine
measure: Part 2: Area Under the Serum Concentration Time Curve from Time 0 to Last Measurable Concentration (AUCt) of Budigalimab
time frame: Up to 12 Weeks
description: Area Under the Plasma Concentration-time Curve from time 0 to last measurable concentration (AUCt) of Budigalimab
measure: Part 2: Time to Cmax (Tmax) of Budigalimab
time frame: Up to 12 Weeks
description: Time to maximum plasma concentration of Budigalimab
measure: Part 2: Time to Cmax (Tmax) of Rovalpituzumab Tesirine
time frame: Up to 12 Weeks
description: Time to maximum plasma concentration of Rovalpituzumab Tesirine
measure: Part 1 and Part 3: Objective response rate (ORR)
time frame: First dose of study drug through at least 30 days after last dose of study drug.
description: ORR is defined as the proportion of subjects with a confirmed partial or complete response to the treatment.
measure: Part 1 and Part 3: Clinical benefit rate (CBR, defined as CR, PR or SD)
time frame: First dose of study drug through at least 30 days after last dose of study drug.
description: CBR defined as the proportion of subjects with a confirmed partial response (PR), complete response (CR), or stable disease.
measure: Part 1 and Part 3: Progression-free survival (PFS)
time frame: First dose of study drug through at least 30 days after last dose of study drug.
description: PFS time is defined as the time from the participant's first dose of study drug (Day 1) to either the participant's disease progression or death, whichever occurs first.
measure: Part 1, Part 2 and Part 3: Duration of objective response (DOR)
time frame: First dose of study drug through at least 30 days after last dose of study drug.
description: DOR for a participant is defined as the time from the participant's initial objective response to study drug therapy to disease progression or death, whichever occurs first.
arm group label: ABBV-181 plus Venetoclax
arm group type: Experimental
description: Venetoclax will be taken once daily beginning 7 days prior to cycle 1 and continuing daily for a 28 day cycle and ABBV-181 will be administered every 4 weeks.
arm group label: ABBV-181
arm group type: Experimental
description: ABBV-181 will be administered at escalating dose levels in 28-day dosing cycles (2 doses per cycle). Based on available safety, pharmacokinetic, and pharmacodynamic data from the dose-escalation part of the study, participants will be enrolled in dose-expansion cohorts to further evaluate ABBV-181 at a dose level which is at or below the Maximum tolerated dose (MTD). In the Monotherapy Expansion portion of the study, ABBV-181 will be administered in 28-day dosing cycles at either 1 dose per cycle or 2 doses per cycle. Based on available safety, PK and PD data from the single agent dose-escalation part of the study, a dose for ABBV-181 will be selected to evaluate in combination with Rovalpituzumab Tesirine or venetoclax.
arm group label: ABBV-181 plus Rovalpituzumab Tesirine
arm group type: Experimental
description: Rovalpituzumab Tesirine will be given once every six weeks times two doses and ABBV-181 will be administered every 3 weeks.
intervention type: Drug
intervention name: Venetoclax
description: Tablet taken orally
arm group label: ABBV-181 plus Venetoclax
intervention type: Drug
intervention name: Rovalpituzumab Tesirine
description: Intravenous infusion
arm group label: ABBV-181 plus Rovalpituzumab Tesirine
intervention type: Drug
intervention name: ABBV-181
description: Intravenous infusion
arm group label: ABBV-181
arm group label: ABBV-181 plus Rovalpituzumab Tesirine
arm group label: ABBV-181 plus Venetoclax
other name: Budigalimab
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: ABBVIE INC.
role: Study Director
affiliation: AbbVie
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: Australia
country: Austria
country: Belgium
country: Canada
country: Finland
country: France
country: Japan
country: Spain
country: Taiwan
country: United States
country: Italy
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Venetoclax
mesh term: Rovalpituzumab tesirine
sharing ipd: No