<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/NCT04429542</url>
  </required_header>
  <id_info>
    <org_study_id>BCA101X1101</org_study_id>
    <secondary_id>KEYNOTE-E28</secondary_id>
    <nct_id>NCT04429542</nct_id>
  </id_info>
  <brief_title>Study of Safety and Tolerability of BCA101 Monotherapy and in Combination Therapy in Patients With EGFR-driven Advanced Solid Tumors</brief_title>
  <official_title>First-in-Human, Phase 1/1b, Open-label, Multicenter Study of Bifunctional EGFR/TGFβ Fusion Protein BCA101 Monotherapy and in Combination Therapy in Patients With EGFR-Driven Advanced Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bicara Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Bicara Therapeutics</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>
      The investigational drug to be studied in this protocol, BCA101, is a first-in-class compound&#xD;
      that targets both EGFR with TGFβ. Based on preclinical data, this bifunctional antibody may&#xD;
      exert synergistic activity in patients with EGFR-driven tumors.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase 1/1b, open-label study, which consists of dose escalation parts (Part A)&#xD;
      followed by expansion cohorts (Part B) for both single agent BCA101 and combination BCA101&#xD;
      plus pembrolizumab.&#xD;
&#xD;
      The study population in dose escalation (Part A) of single agent BCA101 consists of subjects&#xD;
      with EGFR-driven advanced solid tumors refractory to standard of care or for whom no standard&#xD;
      of care is available. Dose escalation (Part A) of combination BCA101 and pembrolizumab&#xD;
      consists of subjects with either Squamous Cell Carcinoma of the Head and Neck (HNSCC) or&#xD;
      Squamous Cell Carcinoma of the Anal Canal (SCCAC) whose tumors are refractory to standard of&#xD;
      care or for whom no standard of care is available.&#xD;
&#xD;
      Once the maximum tolerated dose (MTD) / recommended dose (RD) of single agent BCA101 is&#xD;
      determined, the study will continue with expansion cohorts (Part B) with select tumor types.&#xD;
      Expansion cohorts for single agent BCA101 will include cutaneous squamous cell carcinoma.&#xD;
      Planned expansion cohorts for the combination of BCA101 and pembrolizumab include: 1) HNSCC&#xD;
      and 2) SCCAC.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 1, 2020</start_date>
  <completion_date type="Anticipated">June 1, 2025</completion_date>
  <primary_completion_date type="Anticipated">December 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>Safety of BCA101 alone and BCA101 in combination with pembrolizumab: Incidence and severity of AEs and SAEs</measure>
    <time_frame>24 months</time_frame>
    <description>Incidence and severity of AEs and SAEs</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Tolerability of BCA101 alone and BCA101 in combination with pembrolizumab: Incidence and severity of AEs and SAEs</measure>
    <time_frame>24 months</time_frame>
    <description>Incidence and severity of AEs and SAEs</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of Dose Limiting Toxicities (DLTs)</measure>
    <time_frame>21 days</time_frame>
    <description>Incidence of DLTs during the first cycle of treatment with BCA101 monotherapy or the combination of BCA101 and pembrolizumab.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate</measure>
    <time_frame>24 months</time_frame>
    <description>Determine objective response rate in each part of the study, per RECIST v1.1 and iRECIST</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Benefit Rate</measure>
    <time_frame>24 months</time_frame>
    <description>Determine clinical benefit rate in each part of the study, per RECIST v1.1 and iRECIST</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>24 months</time_frame>
    <description>Determine PFS in each part of the study, per RECIST v1.1 and iRECIST</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response</measure>
    <time_frame>24 months</time_frame>
    <description>Determine duration of response in each part of the study, per RECIST v1.1 and iRECIST</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>24 months</time_frame>
    <description>Determine survival rates in each part of the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC of BCA101 and pembrolizumab</measure>
    <time_frame>24 months</time_frame>
    <description>AUC</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax of BCA101 and pembrolizumab</measure>
    <time_frame>24 months</time_frame>
    <description>Cmax</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax of BCA101 and pembrolizumab</measure>
    <time_frame>24 months</time_frame>
    <description>Tmax</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration vs time profile of BCA101 and pembrolizumab</measure>
    <time_frame>24 months</time_frame>
    <description>Ctrough</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Half-life of BCA101 and pembrolizumab</measure>
    <time_frame>24 months</time_frame>
    <description>Half-life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunogenicity of BCA101 and pembrolizumab</measure>
    <time_frame>24 months</time_frame>
    <description>Incidence and titer of anti-drug-antibodies</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">292</enrollment>
  <condition>Head and Neck Squamous Cell Carcinoma</condition>
  <condition>Squamous Cell Carcinoma of Anal Canal</condition>
  <condition>Colorectal Cancer</condition>
  <condition>Squamous Cell Carcinoma of the Lung</condition>
  <condition>EGFR Amplification</condition>
  <condition>Epithelial Ovarian Cancer</condition>
  <condition>Pancreas Cancer</condition>
  <condition>Cutaneous Squamous Cell Carcinoma</condition>
  <condition>Head and Neck Neoplasms</condition>
  <condition>Carcinoma, Squamous Cell</condition>
  <condition>Squamous Cell Carcinoma of Head and Neck</condition>
  <arm_group>
    <arm_group_label>BCA101 Monotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Route: IV Infusion Frequency: QW Current Dose: 1500mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>BCA101 + pembrolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Route: IV Infusion Frequency: Q3W Dose: 200mg</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BCA101</intervention_name>
    <description>EGFR/TGFβ fusion monoclonal antibody</description>
    <arm_group_label>BCA101 + pembrolizumab</arm_group_label>
    <arm_group_label>BCA101 Monotherapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>anti-PD-1</description>
    <arm_group_label>BCA101 + pembrolizumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient must have measurable disease amendable to biopsy and be willing to undergo&#xD;
             both a pre-treatment and on-treatment biopsy, as well as provide archival tumor if&#xD;
             available from the primary tumor (a paraffin embedded tumor tissue block sufficient to&#xD;
             obtain at least 10 sections of 4 to 5 micrometer thickness).&#xD;
&#xD;
          -  Patient must have a performance status of ≤1 on the Eastern Cooperative Oncology Group&#xD;
             Performance Scale.&#xD;
&#xD;
          -  Patients must have evaluable or measurable disease (computed tomography [CT]/magnetic&#xD;
             resonance imaging [MRI] scans performed within 21 days before the screening visit are&#xD;
             acceptable) demonstrating measurable disease, i.e., at least 1 unidimensional&#xD;
             measurable lesion as defined by Response Evaluation Criteria in Solid Tumors, Version&#xD;
             1.1 (RECIST 1.1) and Immune Response Evaluation Criteria in Solid Tumors (iRECIST).&#xD;
&#xD;
          -  Tumor eligibility:&#xD;
&#xD;
        PART B (Cohort expansion):&#xD;
&#xD;
        i. Single agent BCA101 - patients with the following tumor type will be eligible:&#xD;
&#xD;
        • Expansion Cohort 1: Cutaneous Squamous Cell Carcinoma (CSCC) - i. patients must have&#xD;
        received (or been intolerant to or ineligible for) prior anti-PD-1 therapy in the&#xD;
        metastatic or locally advanced setting.&#xD;
&#xD;
        ii. No prior history of treatment with anti-EGFR antibodies in the unresectable/metastatic&#xD;
        setting (prior treatment with radiotherapy in the adjuvant setting is allowed).&#xD;
&#xD;
        ii. Combination BCA101 and pembrolizumab - patients with the following tumor types will be&#xD;
        eligible:&#xD;
&#xD;
        • Expansion Cohort 2: Head and Neck Squamous Cell Carcinoma (HNSCC), metastatic or&#xD;
        unresectable, recurrent with a Combined Positive Score (CPS) equal to or greater than 1, as&#xD;
        determined by an CLIA-approved laboratory test. Primary tumor locations of oropharynx, oral&#xD;
        cavity, hypopharynx, or larynx. Participants may not have a primary tumor site of&#xD;
        nasopharynx (any histology).&#xD;
&#xD;
        i. Patients must have no prior systemic therapy administered in the recurrent or metastatic&#xD;
        setting (with the exception of systemic therapy completed &gt;6 months prior if given as part&#xD;
        of multimodal treatment for locally advanced disease) or prior history of immune checkpoint&#xD;
        inhibitors with the exception of neoadjuvant therapy (&gt;6 months prior to study drug&#xD;
        initiation). No prior history of anti-EGFR antibodies (with the exception of&#xD;
        radiosensitizing agents and multimodal treatment for locally advanced disease).&#xD;
&#xD;
        ii. Patients must provide tissue for PD-L1 biomarker analysis from a core or excisional&#xD;
        biopsy (fine needle aspirate is not sufficient): A newly obtained biopsy (within 90 days&#xD;
        prior to start of study treatment) is preferred but an archival sample is acceptable.&#xD;
&#xD;
        iii. Patients must have results from testing of human papillomavirus (HPV) status for&#xD;
        oropharyngeal cancer&#xD;
&#xD;
          -  Expansion Cohort 3: Squamous Carcinoma of the Anal Canal (SCAC), locally&#xD;
             advanced/unresectable or metastatic.&#xD;
&#xD;
             i. Patients must have received (or been intolerant to or ineligible for) at least 1&#xD;
             prior line of chemotherapy and received no more than 2 prior lines of systemic&#xD;
             treatments for treatment of unresectable and/or metastatic disease. No prior history&#xD;
             of immune checkpoint inhibitors.&#xD;
&#xD;
          -  Expansion Cohort 5: Squamous Non-Small Cell Lung Cancer (SqNSCLC) i. Patients must&#xD;
             have a histologically or cytologically confirmed diagnosis of stage IV (AJCC 8th&#xD;
             edition) squamous NSCLC. Patients with mixed histology (e.g., adenosquamous) are not&#xD;
             allowed.&#xD;
&#xD;
        ii. Patients must have progressed on one prior systemic therapy in the metastatic setting.&#xD;
&#xD;
        iii. No prior history of treatment with anti-EGFR antibodies in the metastatic setting.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  For Part A: Exposure to anti-EGFR antibodies within 4 weeks of the first dose of study&#xD;
             drug.&#xD;
&#xD;
          -  Prior treatment with any anti-TGFβ therapy.&#xD;
&#xD;
          -  Prior history of Grade ≥ 2 intolerance or hypersensitivity reaction to cetuximab or&#xD;
             other anti-EGFR therapy or other murine proteins or prior discontinuation of therapy&#xD;
             in the setting of toxicity related to treatment.&#xD;
&#xD;
          -  Pregnant or breastfeeding women.&#xD;
&#xD;
          -  Any condition requiring systemic treatment with either corticosteroids (&gt;10 mg daily&#xD;
             of prednisone or equivalent) or other immunosuppressive medication within 14 days&#xD;
             prior to the first dose of study drug, with the exception of topical, intranasal,&#xD;
             intrabronchial, or ocular steroids.&#xD;
&#xD;
          -  Known history of a hematologic malignancy (or solid tumor other than the ones&#xD;
             indicated for this study), unless the patient has undergone potentially curative&#xD;
             therapy with no evidence of that disease for 2 years. Does not include tumors with a&#xD;
             negligible risk of metastasis or death (e.g. adequately treated basal or squamous cell&#xD;
             carcinoma, stage 1 prostate cancer, or carcinoma in situ of the cervix or carcinoma in&#xD;
             situ of the breast). Subjects enrolling in the CSCC cohort may have chronic&#xD;
             lymphocytic leukemia as long as the patient is not on active treatment.&#xD;
&#xD;
          -  Known cases of human immunodeficiency virus (HIV) are excluded if patients have a CD4+&#xD;
             T-cell (CD4+) count &lt;250 cells/uL. To ensure that effective antiretroviral therapy&#xD;
             (ART) is tolerated and that toxicities are not confused with investigational drug&#xD;
             toxicities, trial participants should be on established ART for at least four weeks&#xD;
             and have an HIV viral load less than 400 copies/mL prior to enrollment.&#xD;
&#xD;
          -  Patients with chronic HBV infection with active disease who meet the criteria for&#xD;
             anti-HBV therapy and are not on a suppressive antiviral therapy prior to initiation of&#xD;
             study treatment&#xD;
&#xD;
          -  Patients with a known history of hepatitis C who have not completed curative antiviral&#xD;
             treatment or have a HCV viral load above the limit of quantification&#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_contact>
    <last_name>David Bohr</last_name>
    <phone>6178000335</phone>
    <email>info@bicara.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Moores Cancer Center UC San Diego Health</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Debanjali Ghosh</last_name>
      <phone>858-246-0357</phone>
      <email>d1ghosh@health.ucsd.edu</email>
    </contact>
    <investigator>
      <last_name>Assuntina Sacco, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Keck School of Medicine of USC</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Gino In, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>UCLA</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Deborah Wong, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>H. Lee Moffitt Cancer Center and Research Institute, Inc</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hamza Elmohd</last_name>
      <phone>813-745-5554</phone>
      <email>Hamza.elmohd@moffitt.org</email>
    </contact>
    <investigator>
      <last_name>Jameel Muzaffar, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Dana Farber/Partners Cancer Care Inc</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>DFCI Clinical Trials Hotline</last_name>
      <phone>877-338-7425</phone>
    </contact>
    <investigator>
      <last_name>Glen Hanna, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10017</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <phone>646-608-3759</phone>
    </contact>
    <investigator>
      <last_name>Paul Paik, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Columbia University Herbert Irving Comprehensive Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>CPDM Nurse Navigator</last_name>
      <phone>212-342-5162</phone>
      <email>cancerclinicaltrials@cumc.columbia.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <phone>866-223-8100</phone>
      <email>TaussigResearch@ccf.org</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>UPMC Hillman Cancer Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sarah Brodeur</last_name>
      <email>brodeurs@upmc.edu</email>
    </contact>
    <investigator>
      <last_name>Dan Zanberg, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Rhode Island Hospital</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02903</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Medical University of South Carolina, Hollings Cancer Center</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lilli Neal</last_name>
      <phone>843-792-8113</phone>
      <email>nealli@musc.edu</email>
    </contact>
    <contact_backup>
      <last_name>Carly Fecio</last_name>
      <phone>8437923479</phone>
      <email>fecio@musc.edu</email>
    </contact_backup>
    <investigator>
      <last_name>John Kaczmar, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>MD</last_name>
    </contact>
    <investigator>
      <last_name>Mike Gibson, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Beryl Tross</last_name>
      <phone>713-745-0774</phone>
      <email>bmtross@mdanderson.org</email>
    </contact>
    <investigator>
      <last_name>Van Morris, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Princess Margaret Cancer Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <phone>18007110500</phone>
    </contact>
    <investigator>
      <last_name>Phillippe Bedard, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>June 10, 2020</study_first_submitted>
  <study_first_submitted_qc>June 11, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 12, 2020</study_first_posted>
  <last_update_submitted>July 17, 2023</last_update_submitted>
  <last_update_submitted_qc>July 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>TGFβ</keyword>
  <keyword>EGFR</keyword>
  <keyword>pembrolizumab</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
    <mesh_term>Carcinoma, Ovarian Epithelial</mesh_term>
    <mesh_term>Pancreatic Neoplasms</mesh_term>
    <mesh_term>Head and Neck Neoplasms</mesh_term>
    <mesh_term>Lung Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</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/NCT04429542
org study id: BCA101X1101
secondary id: KEYNOTE-E28
nct id: NCT04429542
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The investigational drug to be studied in this protocol, BCA101, is a first-in-class compound
      that targets both EGFR with TGFβ. Based on preclinical data, this bifunctional antibody may
      exert synergistic activity in patients with EGFR-driven tumors.
This is a Phase 1/1b, open-label study, which consists of dose escalation parts (Part A)
      followed by expansion cohorts (Part B) for both single agent BCA101 and combination BCA101
      plus pembrolizumab.

      The study population in dose escalation (Part A) of single agent BCA101 consists of subjects
      with EGFR-driven advanced solid tumors refractory to standard of care or for whom no standard
      of care is available. Dose escalation (Part A) of combination BCA101 and pembrolizumab
      consists of subjects with either Squamous Cell Carcinoma of the Head and Neck (HNSCC) or
      Squamous Cell Carcinoma of the Anal Canal (SCCAC) whose tumors are refractory to standard of
      care or for whom no standard of care is available.

      Once the maximum tolerated dose (MTD) / recommended dose (RD) of single agent BCA101 is
      determined, the study will continue with expansion cohorts (Part B) with select tumor types.
      Expansion cohorts for single agent BCA101 will include cutaneous squamous cell carcinoma.
      Planned expansion cohorts for the combination of BCA101 and pembrolizumab include: 1) HNSCC
      and 2) SCCAC.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety of BCA101 alone and BCA101 in combination with pembrolizumab: Incidence and severity of AEs and SAEs
time frame: 24 months
description: Incidence and severity of AEs and SAEs
measure: Tolerability of BCA101 alone and BCA101 in combination with pembrolizumab: Incidence and severity of AEs and SAEs
time frame: 24 months
description: Incidence and severity of AEs and SAEs
measure: Incidence of Dose Limiting Toxicities (DLTs)
time frame: 21 days
description: Incidence of DLTs during the first cycle of treatment with BCA101 monotherapy or the combination of BCA101 and pembrolizumab.
measure: Objective Response Rate
time frame: 24 months
description: Determine objective response rate in each part of the study, per RECIST v1.1 and iRECIST
measure: Clinical Benefit Rate
time frame: 24 months
description: Determine clinical benefit rate in each part of the study, per RECIST v1.1 and iRECIST
measure: Progression free survival
time frame: 24 months
description: Determine PFS in each part of the study, per RECIST v1.1 and iRECIST
measure: Duration of Response
time frame: 24 months
description: Determine duration of response in each part of the study, per RECIST v1.1 and iRECIST
measure: Overall Survival
time frame: 24 months
description: Determine survival rates in each part of the study.
measure: AUC of BCA101 and pembrolizumab
time frame: 24 months
description: AUC
measure: Cmax of BCA101 and pembrolizumab
time frame: 24 months
description: Cmax
measure: Tmax of BCA101 and pembrolizumab
time frame: 24 months
description: Tmax
measure: Concentration vs time profile of BCA101 and pembrolizumab
time frame: 24 months
description: Ctrough
measure: Half-life of BCA101 and pembrolizumab
time frame: 24 months
description: Half-life
measure: Immunogenicity of BCA101 and pembrolizumab
time frame: 24 months
description: Incidence and titer of anti-drug-antibodies
arm group label: BCA101 Monotherapy
arm group type: Experimental
description: Route: IV Infusion Frequency: QW Current Dose: 1500mg
arm group label: BCA101 + pembrolizumab
arm group type: Experimental
description: Route: IV Infusion Frequency: Q3W Dose: 200mg
intervention type: Drug
intervention name: BCA101
description: EGFR/TGFβ fusion monoclonal antibody
arm group label: BCA101 + pembrolizumab
arm group label: BCA101 Monotherapy
intervention type: Drug
intervention name: Pembrolizumab
description: anti-PD-1
arm group label: BCA101 + pembrolizumab
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: David Bohr
phone: 6178000335
email: info@bicara.com
facility: 
status: Recruiting
contact: 
investigator: 
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
facility: 
status: Recruiting
contact: 
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investigator: 
facility: 
status: Recruiting
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facility: 
status: Recruiting
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status: Recruiting
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country: Canada
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Squamous Cell Carcinoma of Head and Neck
mesh term: Carcinoma, Ovarian Epithelial
mesh term: Pancreatic Neoplasms
mesh term: Head and Neck Neoplasms
mesh term: Lung Neoplasms
mesh term: Pembrolizumab
sharing ipd: No