xml: <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/NCT06032936</url>
    </required_header>
    <id_info>
      <org_study_id>LB1002-102</org_study_id>
      <nct_id>NCT06032936</nct_id>
    </id_info>
    <brief_title>BBP-398 in Combination With Osimertinib in Locally Advanced or Metastatic NSCLC Patients With EGFR Mutations</brief_title>
    <official_title>An Open-label, Non-randomized, Multi-cohort, Multi-center Phase Ia/Ib Study Evaluating the Efficacy and Safety of BBP-398 in Combination With Osimertinib in Locally Advanced or Metastatic NSCLC Patients With EGFR Mutations</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>LianBio LLC</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>LianBio LLC</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This is an open-label, non-randomized, multi-cohort, multi-center Phase Ia/Ib study for&#xD;
        BBP-398 in combination with Osimertinib to evaluate the safety, tolerability,&#xD;
        pharmacokinetics, determine MTD and/or RP2D, and anti-cancer activity in locally advanced or&#xD;
        metastatic NSCLC patients with EGFR mutations and with previously 3rd generation EGFR-TKIs&#xD;
        treated or EGFR-TKI-naive.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">July 27, 2023</start_date>
    <completion_date type="Anticipated">July 2026</completion_date>
    <primary_completion_date type="Anticipated">December 2025</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Treatment-emergent adverse events (TEAEs)</measure>
      <time_frame>From the first study administration to approximately 28 days after the last study administration</time_frame>
      <description>Incidence and severity of treatment-emergent adverse events (TEAEs).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Serious adverse events (SAEs)</measure>
      <time_frame>Administration to approximately 28 days after the last study administration</time_frame>
      <description>Incidence and severity of Serious adverse events (SAEs)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Phase Ib: ORR assessed by the investigator according to RECIST v1.1</measure>
      <time_frame>Every 8 weeks from first dose administration to the date of progression determined by the investigator or death due to any cause, whichever came first, assessed approximately 48 months.</time_frame>
      <description>ORR is defined as number of patients with confirmed responses of CR or PR, divided by the total number of treated patients with measurable disease at baseline assessed by the investigator.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Phase Ia: QT Interval</measure>
      <time_frame>Approximately 6 months</time_frame>
      <description>Evaluated by comparing the changes using electrocardiogram in the post-dose to the pre-dose.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Maximum plasma concentration (Cmax)</measure>
      <time_frame>Approximately 6 months</time_frame>
      <description>To characterize the pharmacokinetic parameter Maximum plasma concentration (Cmax) of BBP-398 and/or Osimertinib and its metabolites</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Area under the plasma concentration versus time curve (AUC)</measure>
      <time_frame>Approximately 6 months</time_frame>
      <description>To characterize the pharmacokinetic parameter Area under the plasma concentration versus time curve (AUC) of BBP-398 and/or Osimertinib and its metabolites</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to Reach Maximum Plasma Concentration (Tmax)</measure>
      <time_frame>Approximately 6 months</time_frame>
      <description>To characterize the pharmacokinetic parameter time to reach maximum plasma concentration (Tmax) of BBP-398 and/or Osimertinib and its metabolites.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Apparent total plasma clearance (CL/F)</measure>
      <time_frame>Approximately 6 months</time_frame>
      <description>To characterize the pharmacokinetic parameter Apparent total plasma clearance (CL/F) of BBP-398 and/or Osimertinib and its metabolites.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Terminal elimination half-life (t1/2)</measure>
      <time_frame>Approximately 6 months</time_frame>
      <description>To characterize the pharmacokinetic parameter Terminal elimination half-life (t1/2) of BBP-398 and/or Osimertinib and its metabolites.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Accumulation ratio (Racc)</measure>
      <time_frame>Approximately 6 months</time_frame>
      <description>To characterize the pharmacokinetic parameter Accumulation ratio (Racc) of BBP-398 and/or Osimertinib and its metabolites.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Phase Ib: DOR</measure>
      <time_frame>Every 8 weeks from first evaluation as CR or PR to the first evaluation as PD or death of any cause, whichever came first, assessed approximately 24 months.</time_frame>
      <description>DOR assessed by the investigator according to RECIST v1.1. DoR is defined as time interval from the first evaluation as CR or PR to the first evaluation as PD or death of any cause assessed by the investigator (percent of patients with ≥6 months, ≥9 months, and ≥12 months DoR will be reported).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Phase Ib: PFS</measure>
      <time_frame>Every 8 weeks from first evaluation as CR or PR to the first evaluation as PD or death of any cause, whichever came first, assessed approximately 24 months.</time_frame>
      <description>PFS assessed by the investigator according to RECIST v1.1. PFS is defined from the first date of treatment to the date of progression determined by the investigator or death due to any cause (only for dose expansion).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Phase Ib: OS</measure>
      <time_frame>From the first date of treatment until date of death, assessed approximately 48 months.</time_frame>
      <description>including 1-year and 2-years survival rate. OS is defined from the first date of treatment until date of death (only for dose expansion).</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">52</enrollment>
    <condition>NSCLC</condition>
    <arm_group>
      <arm_group_label>BBP-398 + Osimertinib</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Phase Ia (Dose Escalation):&#xD;
  Dose level 1: (starting dose level) The one lower dose level than RP2D of BBP-398 monotherapy in Chinese patients (RP2D -1) with Osimertinib 80 mg Dose level 2: RP2D The same dose level to RP2D of BBP-398 monotherapy in Chinese patients with Osimertinib 80 mg Note: The dosing interval and regimen might be changed based on emerging data of Study NAV-1001, LB1002-101 and this study. The proposed new dosing regimen will be submitted in a memo to EC for approval before execution.&#xD;
  Phase Ib (Efficacy Expansion):&#xD;
  Osimertinib 80mg QD + BBP-398 RP2D QD</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>BBP-398</intervention_name>
      <description>BBP-398 (formerly known as IACS-15509) is a potent, selective, orally active allosteric inhibitor of SHP2, a tyrosine phosphatase that plays a key role in the RTK -MAPK signal transduction pathway. Key components of the MAPK pathway include the small GTPase RAS, the serine/threonine-protein kinase RAF, mitogen-activated protein kinase (MEK) and ERK. In cells, SHP2 binds to phosphorylated tyrosine residues in the intracellular domain of RTKs such as the EGFR, leading to activation of the downstream MAPK signaling pathway.</description>
      <arm_group_label>BBP-398 + Osimertinib</arm_group_label>
      <other_name>IACS-15509</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>osimertinib</intervention_name>
      <description>Osimertinib is a mutant-selective, third-generation EGFR inhibitor that targets both EGFR-activating mutations (e.g., exon 19 deletion and L858R) and EGFR-dependent on-target resistance mutation toward the 1st generation EGFR inhibitor (i.e., T790M). It is currently a first-line therapy for EGFR-mutant (EGFRmut) NSCLC, with average progression-free survival of approximately 19 months in previously untreated subjects.</description>
      <arm_group_label>BBP-398 + Osimertinib</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Patients must have the ability to understand and the willingness to sign a written&#xD;
               informed consent document.&#xD;
  &#xD;
            -  Patients must be willing and able to comply with the scheduled visits, treatment plan,&#xD;
               laboratory tests and other specified study procedures.&#xD;
  &#xD;
            -  Age ≥18, male or female.&#xD;
  &#xD;
            -  Patients are not suitable for surgical resection and must have histologically or&#xD;
               cytologically confirmed advanced or metastatic NSCLC with documented EGFR sensitivity&#xD;
               mutation (at any time since the initial diagnosis of NSCLC) to confirm susceptibility&#xD;
               to EGFR-TKI therapy.&#xD;
  &#xD;
            -  Patients must have measurable disease by RECIST v1.1.&#xD;
  &#xD;
            -  ECOG performance status ≤2.&#xD;
  &#xD;
            -  Patients must have a life expectancy of ≥12 weeks as estimated at the time of&#xD;
               screening.&#xD;
  &#xD;
            -  Patients must have adequate organ function.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patients with a known additional malignancy that is progressing or requires active&#xD;
               treatment.&#xD;
  &#xD;
            -  Patients who have previously received a SHP-2 inhibitor.&#xD;
  &#xD;
            -  Patients who are hypersensitivity to BBP-398/ Osimertinib or active or inactive&#xD;
               excipients.&#xD;
  &#xD;
            -  Treatment with any of the following anti-cancer therapies prior to the first dose&#xD;
               within the stated timeframes.&#xD;
  &#xD;
            -  Pregnant or breastfeeding female patients.&#xD;
  &#xD;
            -  Patients with untreated symptomatic brain metastases and/or meningeal metastases.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>99 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Li Zhang, Master</last_name>
      <role>Principal Investigator</role>
      <affiliation>Sun Yat-sen University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Lei Mu, Master</last_name>
      <phone>+86-021-23081188</phone>
      <email>lei.mu@lianbio.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Beijing Cancer Hospital</name>
        <address>
          <city>Beijing</city>
          <state>Beijing</state>
          <zip>100142</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Jun Zhao</last_name>
        <phone>+8613521469355</phone>
        <email>ohjerry@163.com</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Sun Yat-sen University Cancer Center</name>
        <address>
          <city>Guanzhou</city>
          <state>Guangdong</state>
          <zip>510060</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Li Zhang, Master</last_name>
        <phone>+86-020-87343458</phone>
        <email>zhangli@sysucc.org.cn</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Jilin Cancer Hospital</name>
        <address>
          <city>Changchun</city>
          <state>Jilin</state>
          <zip>130012</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Ying Cheng</last_name>
        <phone>+8613943012851</phone>
        <email>jl.cheng@163.com</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Shandong Cancer Hospital</name>
        <address>
          <city>Jinan</city>
          <state>Shandong</state>
          <zip>250117</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Yintao Li</last_name>
        <phone>+8615169045166</phone>
        <email>liyintaosky@gmail.com</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>West China Hospital Sichuan University</name>
        <address>
          <city>Chengdu</city>
          <state>Sichuan</state>
          <zip>610041</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Yongsheng Wang, Doctor</last_name>
        <phone>+8618980602258</phone>
        <email>wangy756@163.com</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>July 31, 2023</study_first_submitted>
    <study_first_submitted_qc>September 4, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 13, 2023</study_first_posted>
    <last_update_submitted>September 4, 2023</last_update_submitted>
    <last_update_submitted_qc>September 4, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 13, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Osimertinib</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06032936
  org study id: LB1002-102
  nct id: NCT06032936
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This is an open-label, non-randomized, multi-cohort, multi-center Phase Ia/Ib study for
        BBP-398 in combination with Osimertinib to evaluate the safety, tolerability,
        pharmacokinetics, determine MTD and/or RP2D, and anti-cancer activity in locally advanced or
        metastatic NSCLC patients with EGFR mutations and with previously 3rd generation EGFR-TKIs
        treated or EGFR-TKI-naive.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Treatment-emergent adverse events (TEAEs)
  time frame: From the first study administration to approximately 28 days after the last study administration
  description: Incidence and severity of treatment-emergent adverse events (TEAEs).
  measure: Serious adverse events (SAEs)
  time frame: Administration to approximately 28 days after the last study administration
  description: Incidence and severity of Serious adverse events (SAEs)
  measure: Phase Ib: ORR assessed by the investigator according to RECIST v1.1
  time frame: Every 8 weeks from first dose administration to the date of progression determined by the investigator or death due to any cause, whichever came first, assessed approximately 48 months.
  description: ORR is defined as number of patients with confirmed responses of CR or PR, divided by the total number of treated patients with measurable disease at baseline assessed by the investigator.
  measure: Phase Ia: QT Interval
  time frame: Approximately 6 months
  description: Evaluated by comparing the changes using electrocardiogram in the post-dose to the pre-dose.
  measure: Maximum plasma concentration (Cmax)
  time frame: Approximately 6 months
  description: To characterize the pharmacokinetic parameter Maximum plasma concentration (Cmax) of BBP-398 and/or Osimertinib and its metabolites
  measure: Area under the plasma concentration versus time curve (AUC)
  time frame: Approximately 6 months
  description: To characterize the pharmacokinetic parameter Area under the plasma concentration versus time curve (AUC) of BBP-398 and/or Osimertinib and its metabolites
  measure: Time to Reach Maximum Plasma Concentration (Tmax)
  time frame: Approximately 6 months
  description: To characterize the pharmacokinetic parameter time to reach maximum plasma concentration (Tmax) of BBP-398 and/or Osimertinib and its metabolites.
  measure: Apparent total plasma clearance (CL/F)
  time frame: Approximately 6 months
  description: To characterize the pharmacokinetic parameter Apparent total plasma clearance (CL/F) of BBP-398 and/or Osimertinib and its metabolites.
  measure: Terminal elimination half-life (t1/2)
  time frame: Approximately 6 months
  description: To characterize the pharmacokinetic parameter Terminal elimination half-life (t1/2) of BBP-398 and/or Osimertinib and its metabolites.
  measure: Accumulation ratio (Racc)
  time frame: Approximately 6 months
  description: To characterize the pharmacokinetic parameter Accumulation ratio (Racc) of BBP-398 and/or Osimertinib and its metabolites.
  measure: Phase Ib: DOR
  time frame: Every 8 weeks from first evaluation as CR or PR to the first evaluation as PD or death of any cause, whichever came first, assessed approximately 24 months.
  description: DOR assessed by the investigator according to RECIST v1.1. DoR is defined as time interval from the first evaluation as CR or PR to the first evaluation as PD or death of any cause assessed by the investigator (percent of patients with ≥6 months, ≥9 months, and ≥12 months DoR will be reported).
  measure: Phase Ib: PFS
  time frame: Every 8 weeks from first evaluation as CR or PR to the first evaluation as PD or death of any cause, whichever came first, assessed approximately 24 months.
  description: PFS assessed by the investigator according to RECIST v1.1. PFS is defined from the first date of treatment to the date of progression determined by the investigator or death due to any cause (only for dose expansion).
  measure: Phase Ib: OS
  time frame: From the first date of treatment until date of death, assessed approximately 48 months.
  description: including 1-year and 2-years survival rate. OS is defined from the first date of treatment until date of death (only for dose expansion).
  arm group label: BBP-398 + Osimertinib
  arm group type: Experimental
  description: Phase Ia (Dose Escalation):
  Dose level 1: (starting dose level) The one lower dose level than RP2D of BBP-398 monotherapy in Chinese patients (RP2D -1) with Osimertinib 80 mg Dose level 2: RP2D The same dose level to RP2D of BBP-398 monotherapy in Chinese patients with Osimertinib 80 mg Note: The dosing interval and regimen might be changed based on emerging data of Study NAV-1001, LB1002-101 and this study. The proposed new dosing regimen will be submitted in a memo to EC for approval before execution.
  Phase Ib (Efficacy Expansion):
  Osimertinib 80mg QD + BBP-398 RP2D QD
  intervention type: Drug
  intervention name: BBP-398
  description: BBP-398 (formerly known as IACS-15509) is a potent, selective, orally active allosteric inhibitor of SHP2, a tyrosine phosphatase that plays a key role in the RTK -MAPK signal transduction pathway. Key components of the MAPK pathway include the small GTPase RAS, the serine/threonine-protein kinase RAF, mitogen-activated protein kinase (MEK) and ERK. In cells, SHP2 binds to phosphorylated tyrosine residues in the intracellular domain of RTKs such as the EGFR, leading to activation of the downstream MAPK signaling pathway.
  arm group label: BBP-398 + Osimertinib
  other name: IACS-15509
  intervention type: Drug
  intervention name: osimertinib
  description: Osimertinib is a mutant-selective, third-generation EGFR inhibitor that targets both EGFR-activating mutations (e.g., exon 19 deletion and L858R) and EGFR-dependent on-target resistance mutation toward the 1st generation EGFR inhibitor (i.e., T790M). It is currently a first-line therapy for EGFR-mutant (EGFRmut) NSCLC, with average progression-free survival of approximately 19 months in previously untreated subjects.
  arm group label: BBP-398 + Osimertinib
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 99 Years
  healthy volunteers: No
  last name: Li Zhang, Master
  role: Principal Investigator
  affiliation: Sun Yat-sen University
  last name: Lei Mu, Master
  phone: +86-021-23081188
  email: lei.mu@lianbio.com
  facility: 
  status: Not yet recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Not yet recruiting
  contact: 
  facility: 
  status: Not yet recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Sponsor
  mesh term: Carcinoma, Non-Small-Cell Lung
  mesh term: Osimertinib