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/NCT06015568</url>
    </required_header>
    <id_info>
      <org_study_id>BTP-21712</org_study_id>
      <nct_id>NCT06015568</nct_id>
    </id_info>
    <brief_title>Study of MCLA-129 Combined With Befotertinib in the Treatment of Advanced Non-small Cell Lung Cancer With EGFR Sensitive Mutation</brief_title>
    <official_title>Phase I Study of Anti-EGFR/c-Met Bispecific Antibody MCLA-129 Combined With Befotertinib in Patients of Advanced Non-small Cell Lung Cancer With EGFR Sensitive Mutation To Evaluate The Safety, Pharmacokinetic Characteristics and Antitumor Activity</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Betta Pharmaceuticals Co., Ltd.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Betta Pharmaceuticals Co., Ltd.</source>
    <oversight_info>
      <has_dmc>Yes</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>
        To evaluate the safety and tolerance of MCLA-129 combined with Befotertinib in patients with&#xD;
        advanced non-small cell lung cancer with EGFR-sensitive mutations.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a phase I study to evaluate the safety, pharmacokinetic characteristics and antitumor&#xD;
        activity of anti-EGFR/c-Met bispecific antibody MCLA-129(1500mg Q2W IV or 2000mg Q2W IV)&#xD;
        combined with Befotertinib (75 mg once daily for first cycle, then increased to 100 mg once&#xD;
        daily, orally) in Patients of advanced non-small cell lung cancer with exon 19 deletion or&#xD;
        exon 21 L858R mutation(either alone or in combination with other EGFR mutations).&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">July 4, 2029</completion_date>
    <primary_completion_date type="Anticipated">November 4, 2028</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>Dose-Limiting Toxicity (DLT)</measure>
      <time_frame>First 28 days of treatment</time_frame>
      <description>To determine the dose-limiting toxicity (DLT) of MCLA-129 combined with Befotertinib in patients of advanced non-small cell lung cancer with EGFR-sensitive mutations in Part 1.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Maximum Tolerable Dose (MTD)</measure>
      <time_frame>First 28 days of treatment</time_frame>
      <description>To determine the maximum tolerated dose (MTD) of MCLA-129 combined with Befotertinib in patients of advanced non-small cell lung cancer with EGFR-sensitive mutations in Part 1.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Treatment-Emergent Adverse Event (TEAE) in Part 1</measure>
      <time_frame>Until 30 days after the last dosing</time_frame>
      <description>To evaluate the safety of MCLA-129 combined with Befotertinib in patients of advanced non-small cell lung cancer with EGFR-sensitive mutations in Part 1 in terms of treatment-emergent adverse event (TEAE).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Overall Response Rate (ORR) in Part 2</measure>
      <time_frame>From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years</time_frame>
      <description>To evaluate the efficacy of MCLA-129 combined with Befotertinib at RP2CD in patients of advanced NSCLC with EGFR-sensitive mutations in each corhort in Part 2 in terms of overall response rate (ORR)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Overall Response Rate (ORR) in Part 1</measure>
      <time_frame>From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years</time_frame>
      <description>To evaluate the efficacy of MCLA-129 combined with Befotertinib at RP2CD in patients of advanced NSCLC with EGFR-sensitive mutations in each corhort in Part 1 in terms of overall response rate (ORR).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease Control Rate (DCR) in Part 1 and 2</measure>
      <time_frame>From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years</time_frame>
      <description>To evaluate the efficacy of MCLA-129 combined with Befotertinib at RP2CD in patients of advanced NSCLC with EGFR-sensitive mutations in patients with advanced NSCLC and other solid tumors in Part 1 and 2 in terms of disease control rate (DCR).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression-Free Survival (PFS) in Part 1 and 2</measure>
      <time_frame>From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years</time_frame>
      <description>To evaluate the efficacy of MCLA-129 combined with Befotertinib at RP2CD in patients of advanced NSCLC with EGFR-sensitive mutations in patients with advanced NSCLC and other solid tumors in Part 1 and 2 in terms of Progression-free survival (PFS).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of Response (DOR) in Part 1 and 2</measure>
      <time_frame>From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years</time_frame>
      <description>To evaluate the efficacy of MCLA-129 combined with Befotertinib at RP2CD in patients of advanced NSCLC with EGFR-sensitive mutations in patients with advanced NSCLC and other solid tumors in Part 1 and 2 in terms of duration of response (DOR).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Anti-Drug Antibody (ADA) in Part 1 and 2</measure>
      <time_frame>Until 30 days after the last dosing</time_frame>
      <description>To assess the Incidence of anti-drug antibodies in serum blood against MCLA-129 following administration of MCLA-129.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall Survival (OS) in Part 2</measure>
      <time_frame>From date of first treatment every 6 weeks until death or withdrawal, whichever came first, approximately 2 years</time_frame>
      <description>To evaluate the efficacy of MCLA-129 combined with Befotertinib at RP2CD in patients of advanced NSCLC with EGFR-sensitive mutations in Part 2 in terms of overall survival (OS).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Treatment-Emergent Adverse Event (TEAE) in and 2</measure>
      <time_frame>Until 30 days after the last dosing</time_frame>
      <description>To evaluate the safety of MCLA-129 combined with Befotertinib in patients of advanced non-small cell lung cancer with EGFR-sensitive mutations in Part 2 in terms of treatment-emergent adverse event (TEAE).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Maximum plasma concentration [Cmax]</measure>
      <time_frame>Until 30 days after the last dosing</time_frame>
      <description>To evaluate the PK profile of MCLA-129 combined with Befotertinib in patients dvanced NSCLC with EGFR-sensitive mutations in Part 1.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to reach maximum concentration [Tmax]</measure>
      <time_frame>Until 30 days after the last dosing</time_frame>
      <description>To evaluate the PK profile of MCLA-129 combined with Befotertinib in patients dvanced NSCLC with EGFR-sensitive mutations in Part 1.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Trough concentration [Ctrough]</measure>
      <time_frame>Until 30 days after the last dosing</time_frame>
      <description>To evaluate the PK profile of MCLA-129 combined with Befotertinib in patients dvanced NSCLC with EGFR-sensitive mutations in Part 1.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Area under the concentration [AUC]</measure>
      <time_frame>Until 30 days after the last dosing</time_frame>
      <description>To evaluate the PK profile of MCLA-129 combined with Befotertinib in patients dvanced NSCLC with EGFR-sensitive mutations in Part 1.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">172</enrollment>
    <condition>Non-Small Cell Lung Cancer、EGFR Sensitive Mutation</condition>
    <arm_group>
      <arm_group_label>MCLA-129+ Befotertinib</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Drug:MCLA-129 1500mg or 2000mg IV Q2W Other name:MCLA-129 Drug:Befotertinib (75 mg or 100 mg orally, once daily) Other name:D-0316</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>MCLA-129: 1500mg or 2000mg IV Q2W</intervention_name>
      <description>Every 28 days is a cycle until disease progression, death, initiation of new anti-tumor treatment, loss of follow-up, or voluntary withdrawal occurs</description>
      <arm_group_label>MCLA-129+ Befotertinib</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Befotertinib: 75 mg or 100 mg Po QD</intervention_name>
      <description>The initial dose of Befotertinib is 75 mg orally once daily (QD) for one cycle, and then increased to 100 mg orally QD in the absence of CTCAE grade ≥ 2 headache or thrombocytopenia during the first cycle, otherwise maintained to 75 mg orally QD.&#xD;
  Every 28 days is a cycle until disease progression, death, initiation of new anti-tumor treatment, loss of follow-up, or voluntary withdrawal occurs.</description>
      <arm_group_label>MCLA-129+ Befotertinib</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Age from 18 to 75 years.&#xD;
  &#xD;
            -  Histologically or cytologically confirmed locally advanced or metastatic NSCLC that is&#xD;
               not suitable for radical surgery or radiotherapy, and harbored EGFR exon 19 deletion&#xD;
               or exon 21 L858R mutation( either alone or in combination with other EGFR mutations)&#xD;
               in NSCLC assessed by genetic testing.&#xD;
  &#xD;
            -  For Part 1: patients with advanced NSCLC must be progression, or intolerance, or&#xD;
               rejected to standard therapy(subjects treated with Befotertinib must be progression of&#xD;
               the disease).&#xD;
  &#xD;
            -  For Part 2, each cohort is defined as follows:&#xD;
  &#xD;
                 -  Cohort A: Previously diagnosed EGFR-sensitive mutations and no systemic antitumor&#xD;
                    therapy for locally advanced or metastatic NSCLC.&#xD;
  &#xD;
                 -  Cohort B: Advanced NSCLC patients with previously diagnosed EGFR-sensitive&#xD;
                    mutations and third generation EGFR-TKI resistance.&#xD;
  &#xD;
                 -  Cohort C: Advanced NSCLC patients who had previously been diagnosed with&#xD;
                    EGFR-sensitive mutations and first or second EGFR-TKI resistance.&#xD;
  &#xD;
          Patients in cohorts B and C must also resistance, or intolerance, or rejection of&#xD;
          platinum-containing chemotherapy.&#xD;
  &#xD;
          •Patients of the dose escalation phase in Part 1 must have evaluable diseases, and others&#xD;
          must have measurable diseases as defined in RECIST V1.1 definition.&#xD;
  &#xD;
          Note: The selected target lesions must meet one of two criteria: 1) no previous local&#xD;
          treatment or 2) subsequent progression within the previous local treatment area as&#xD;
          determined by RECIST V1.1.&#xD;
  &#xD;
            -  Eastern Cooperative Oncology Group (ECOG) performance status scores are 0-1.&#xD;
  &#xD;
            -  Expected survival is ≥3 months.&#xD;
  &#xD;
            -  With certain organ system functions (without transfusion, use of blood components, or&#xD;
               G-CSF support within 14 days before testing), as defined below:&#xD;
  &#xD;
          oAbsolute neutrophil count (ANC)≥1.5×10^9/L oPlatelet count (PLT)≥100×10^9/L oHemoglobin&#xD;
          (HB)≥10 g/dL oSerum albumin≥30 g/L oTotal bilirubin≤1.5 times the upper limit of normal&#xD;
          (ULN) oAlanine amino transferase ( ALT) and aspartate amino transferase (AST) ≤3×ULN&#xD;
          oCreatinine≤1.5×ULN.If creatinine is&gt;1.5×ULN, creatinine clearance is≥50 mL/min as&#xD;
          calculated by Cockcroft-Gault formula, or urinary creatinine clearance≥50 mL/min within 24&#xD;
          hours as measured, the patients can still be enrolled.&#xD;
  &#xD;
            -  Willing and able to follow the trial and follow-up procedures.&#xD;
  &#xD;
            -  Capable of understanding the trial nature and voluntarily signing the written informed&#xD;
               consent form.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Use of certain investigational drug or antineoplastic agent within 14 days or 5 half&#xD;
               lives (whichever is longer) before first administration of investigational drug (For&#xD;
               drugs with a longer half-life, a maximum of 4 weeks is required from the last&#xD;
               administration; 6 weeks for chemotherapy with delayed toxicity, such as Nitroso urea&#xD;
               or Mitomycin C).&#xD;
  &#xD;
            -  Execution of large surgery and radiotherapy (except focal palliative radiotherapy at&#xD;
               least 2 weeks before first administration) within 4 weeks before first administration.&#xD;
  &#xD;
            -  For the dose extension stage of part 2 and part 2: having previously received systemic&#xD;
               anti-tumor therapy exceeding three lines (excluding maintenance therapy).&#xD;
  &#xD;
            -  Previously received EGFR/c-Met bispecific antibody drugs (such as JNJ-61186372,&#xD;
               EMB-01, or GB263T) for treatment.&#xD;
  &#xD;
            -  Prior to the first administration of the study drug, previous treatment-related toxic&#xD;
               reactions did not alleviate to level 1 or below (CTCAE 5.0 standard), except for hair&#xD;
               loss.&#xD;
  &#xD;
            -  With other malignant tumors in the past 3 years, except cancers that have been cured&#xD;
               significantly or can be focally cured, e.g. basosquamous carcinoma of skin, carcinoma&#xD;
               cervix in situ, or in situ breast carcinoma.&#xD;
  &#xD;
            -  Primary malignant tumor of the central nervous system, meningeal metastasis, or brain&#xD;
               metastasis with spinal cord compression, or risk of cerebral hemorrhage, or&#xD;
               symptomatic brain metastasis, or unstable brain metastasis requiring steroid and/or&#xD;
               dehydration to reduce intracranial pressure 2 weeks before enrollment (subjects with&#xD;
               brain metastases who are Asymptomatic or stable for more than 2 weeks after treatment&#xD;
               and do not need steroids and/or dehydration to reduce intracranial pressure can be&#xD;
               included in the group).&#xD;
  &#xD;
            -  With clinically significant cardiovascular disorder, including but not limited to:&#xD;
  &#xD;
                 -  Arterial thromboembolism, deep vein thrombosis or lung embolism diagnosed within&#xD;
                    3 month before first administration of the investigational drug. Non- obstructive&#xD;
                    catheter related clot and other clinically irrelevant thrombosis are not included&#xD;
                    in the exclusion criteria. Patients with a history of related thrombosis&#xD;
                    diagnosed 3 months ago must be clinically stable for at least 4 weeks before&#xD;
                    initial administration.&#xD;
  &#xD;
                 -  With any of the following medical history within 6 months before first&#xD;
                    administration of the investigational drug: myocardial infarction, unstable&#xD;
                    angina, stroke, transient ischemic attack, coronary or peripheral artery bypass,&#xD;
                    or any acute coronary syndrome.&#xD;
  &#xD;
                 -  With abnormal ECG corrected QT interval (QTcF) at rest in the screening period.&#xD;
                    Remeasurement is made twice at intervals of more than 5 minutes. For average QTcF&#xD;
                    of 3 times ECG inspections: male: ≥ 450 msec, and female: ≥ 470 msec. With&#xD;
                    clinically significant abnormal heart rate, conduction, and ECG form at rest,&#xD;
                    e.g. complete left bundle branch block, third-degree conduction block,&#xD;
                    second-degree conduction block, and PR interval &gt; 250 msec, double law, triple&#xD;
                    law, preexcitation syndrome, etc.&#xD;
  &#xD;
                 -  Poorly controlled hypertension in the investigator's opinion (systolic blood&#xD;
                    pressure &gt; 180 mmHg, or diastolic blood pressure &gt; 100 mmHg).&#xD;
  &#xD;
                 -  New York Heart Association Grade III-IV congestive heart failure, or&#xD;
                    hospitalization due to congestive heart failure within 6 months before first&#xD;
                    administration of the investigational drug.&#xD;
  &#xD;
                 -  Pericarditis/clinically significant pericardial effusion.&#xD;
  &#xD;
                 -  Cardiomyopathy.&#xD;
  &#xD;
                 -  ther clinically significant cardiovascular disordesr as believed by&#xD;
                    investigators.&#xD;
  &#xD;
            -  Active hepatitis B (hepatitis B surface antigen (HBsAg) positive and serum HBV DNA&#xD;
               quantitative results higher than or equal to the detection limit), hepatitis C virus&#xD;
               antibody, HIV antibody and treponema pallidum antibody positive (subjects who have a&#xD;
               history of HCV and have completed antiviral treatment, and whose laboratory test&#xD;
               results show that HCV-RNA is below the lower limit of quantification, can be selected&#xD;
               for the study; those who test negative for syphilis titer can be selected).&#xD;
  &#xD;
            -  Patients with Interstitial lung disease, including drug-induced Interstitial lung&#xD;
               disease or radiation pneumonia requiring long-term use of steroids or other&#xD;
               Immunosuppressive drug in the past 1 year.&#xD;
  &#xD;
            -  Subjects with active gastrointestinal (GI) disease, or with a risk of GI perforation,&#xD;
               or with other diseases that significantly interfere with the absorption, distribution,&#xD;
               metabolism, or excretion of investigational drugs. Including but not limited to:&#xD;
               unable to take oral medicine, uncontrollable nausea or vomiting, Bowel obstruction,&#xD;
               inflammatory bowel disease or extensive intestinal resection, etc.&#xD;
  &#xD;
            -  Current severe disease or medical condition, including but not limited to uncontrolled&#xD;
               active infection, uncontrollable pleural or abdominal effusion, and clinically&#xD;
               significant lung, metabolic or psychiatric disorders.&#xD;
  &#xD;
            -  Women with child bearing potential, pregnant women or lactating women with pregnancy&#xD;
               test positive 7 days before treatment, and male and female unwilling to take effective&#xD;
               contraception measures or having a birth plan during the treatment and within 3 months&#xD;
               after end of treatment.&#xD;
  &#xD;
            -  Subjects with a history of allergies or suspected allergic symptoms to the study drug&#xD;
               MCLA-129, Befotertinib, or any component of both study drugs (see the investigator's&#xD;
               brochure).&#xD;
  &#xD;
            -  Within one week before the first administration of the investigational drug, it is&#xD;
               currently in use or needs to be combined with CYP3A strong inhibitors or inducers&#xD;
               during the study period.&#xD;
  &#xD;
            -  Subjects still using Warfarin within 7 days before the first administration (low&#xD;
               molecular weight heparin sodium is allowed).&#xD;
  &#xD;
            -  Patients poorly compliant, unable or unwilling to follow the study and/or follow-up&#xD;
               procedures listed in the protocol, or unsuitable to participate in this trial in the&#xD;
               investigator's opinion.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Shun Lu, M.D.</last_name>
      <role>Study Chair</role>
      <affiliation>Shanghai Chest Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Dandan Zhang, Master</last_name>
      <phone>+86 18626898205</phone>
      <email>dandan.zhang@bettapharma.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>The first affiliated hospital of bengbu medical college</name>
        <address>
          <city>Bengbu</city>
          <state>Anhui</state>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Wei Li, M.D.</last_name>
        <phone>+86 13965282263</phone>
        <email>bbmcliwei@126.com</email>
      </contact>
      <contact_backup>
        <last_name>Yuanyuan Liu, Bachelor</last_name>
        <phone>+86 18955225050</phone>
        <email>120952297@qq.com</email>
      </contact_backup>
    </location>
    <location>
      <facility>
        <name>Hunan cancer hospital</name>
        <address>
          <city>Changsha</city>
          <state>Hunan</state>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Lin Wu, M.D.</last_name>
        <phone>+86 13170419973</phone>
        <email>wulin-calf@vip.163.com</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Shanghai chest hospital</name>
        <address>
          <city>Shanghai</city>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Shun Lu, M.D.</last_name>
        <phone>00-021-22200000-2153</phone>
        <email>Shun_lu@hotmail.com</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 21, 2023</study_first_submitted>
    <study_first_submitted_qc>August 28, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 29, 2023</study_first_posted>
    <last_update_submitted>August 28, 2023</last_update_submitted>
    <last_update_submitted_qc>August 28, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 29, 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>Lung Neoplasms</mesh_term>
      <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
      <mesh_term>Hypersensitivity</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- 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/NCT06015568
  org study id: BTP-21712
  nct id: NCT06015568
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  To evaluate the safety and tolerance of MCLA-129 combined with Befotertinib in patients with
        advanced non-small cell lung cancer with EGFR-sensitive mutations.
  This is a phase I study to evaluate the safety, pharmacokinetic characteristics and antitumor
        activity of anti-EGFR/c-Met bispecific antibody MCLA-129(1500mg Q2W IV or 2000mg Q2W IV)
        combined with Befotertinib (75 mg once daily for first cycle, then increased to 100 mg once
        daily, orally) in Patients of advanced non-small cell lung cancer with exon 19 deletion or
        exon 21 L858R mutation(either alone or in combination with other EGFR mutations).
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Dose-Limiting Toxicity (DLT)
  time frame: First 28 days of treatment
  description: To determine the dose-limiting toxicity (DLT) of MCLA-129 combined with Befotertinib in patients of advanced non-small cell lung cancer with EGFR-sensitive mutations in Part 1.
  measure: Maximum Tolerable Dose (MTD)
  time frame: First 28 days of treatment
  description: To determine the maximum tolerated dose (MTD) of MCLA-129 combined with Befotertinib in patients of advanced non-small cell lung cancer with EGFR-sensitive mutations in Part 1.
  measure: Treatment-Emergent Adverse Event (TEAE) in Part 1
  time frame: Until 30 days after the last dosing
  description: To evaluate the safety of MCLA-129 combined with Befotertinib in patients of advanced non-small cell lung cancer with EGFR-sensitive mutations in Part 1 in terms of treatment-emergent adverse event (TEAE).
  measure: Overall Response Rate (ORR) in Part 2
  time frame: From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years
  description: To evaluate the efficacy of MCLA-129 combined with Befotertinib at RP2CD in patients of advanced NSCLC with EGFR-sensitive mutations in each corhort in Part 2 in terms of overall response rate (ORR)
  measure: Overall Response Rate (ORR) in Part 1
  time frame: From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years
  description: To evaluate the efficacy of MCLA-129 combined with Befotertinib at RP2CD in patients of advanced NSCLC with EGFR-sensitive mutations in each corhort in Part 1 in terms of overall response rate (ORR).
  measure: Disease Control Rate (DCR) in Part 1 and 2
  time frame: From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years
  description: To evaluate the efficacy of MCLA-129 combined with Befotertinib at RP2CD in patients of advanced NSCLC with EGFR-sensitive mutations in patients with advanced NSCLC and other solid tumors in Part 1 and 2 in terms of disease control rate (DCR).
  measure: Progression-Free Survival (PFS) in Part 1 and 2
  time frame: From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years
  description: To evaluate the efficacy of MCLA-129 combined with Befotertinib at RP2CD in patients of advanced NSCLC with EGFR-sensitive mutations in patients with advanced NSCLC and other solid tumors in Part 1 and 2 in terms of Progression-free survival (PFS).
  measure: Duration of Response (DOR) in Part 1 and 2
  time frame: From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years
  description: To evaluate the efficacy of MCLA-129 combined with Befotertinib at RP2CD in patients of advanced NSCLC with EGFR-sensitive mutations in patients with advanced NSCLC and other solid tumors in Part 1 and 2 in terms of duration of response (DOR).
  measure: Anti-Drug Antibody (ADA) in Part 1 and 2
  time frame: Until 30 days after the last dosing
  description: To assess the Incidence of anti-drug antibodies in serum blood against MCLA-129 following administration of MCLA-129.
  measure: Overall Survival (OS) in Part 2
  time frame: From date of first treatment every 6 weeks until death or withdrawal, whichever came first, approximately 2 years
  description: To evaluate the efficacy of MCLA-129 combined with Befotertinib at RP2CD in patients of advanced NSCLC with EGFR-sensitive mutations in Part 2 in terms of overall survival (OS).
  measure: Treatment-Emergent Adverse Event (TEAE) in and 2
  time frame: Until 30 days after the last dosing
  description: To evaluate the safety of MCLA-129 combined with Befotertinib in patients of advanced non-small cell lung cancer with EGFR-sensitive mutations in Part 2 in terms of treatment-emergent adverse event (TEAE).
  measure: Maximum plasma concentration [Cmax]
  time frame: Until 30 days after the last dosing
  description: To evaluate the PK profile of MCLA-129 combined with Befotertinib in patients dvanced NSCLC with EGFR-sensitive mutations in Part 1.
  measure: Time to reach maximum concentration [Tmax]
  time frame: Until 30 days after the last dosing
  description: To evaluate the PK profile of MCLA-129 combined with Befotertinib in patients dvanced NSCLC with EGFR-sensitive mutations in Part 1.
  measure: Trough concentration [Ctrough]
  time frame: Until 30 days after the last dosing
  description: To evaluate the PK profile of MCLA-129 combined with Befotertinib in patients dvanced NSCLC with EGFR-sensitive mutations in Part 1.
  measure: Area under the concentration [AUC]
  time frame: Until 30 days after the last dosing
  description: To evaluate the PK profile of MCLA-129 combined with Befotertinib in patients dvanced NSCLC with EGFR-sensitive mutations in Part 1.
  arm group label: MCLA-129+ Befotertinib
  arm group type: Experimental
  description: Drug:MCLA-129 1500mg or 2000mg IV Q2W Other name:MCLA-129 Drug:Befotertinib (75 mg or 100 mg orally, once daily) Other name:D-0316
  intervention type: Drug
  intervention name: MCLA-129: 1500mg or 2000mg IV Q2W
  description: Every 28 days is a cycle until disease progression, death, initiation of new anti-tumor treatment, loss of follow-up, or voluntary withdrawal occurs
  arm group label: MCLA-129+ Befotertinib
  intervention type: Drug
  intervention name: Befotertinib: 75 mg or 100 mg Po QD
  description: The initial dose of Befotertinib is 75 mg orally once daily (QD) for one cycle, and then increased to 100 mg orally QD in the absence of CTCAE grade ≥ 2 headache or thrombocytopenia during the first cycle, otherwise maintained to 75 mg orally QD.
  Every 28 days is a cycle until disease progression, death, initiation of new anti-tumor treatment, loss of follow-up, or voluntary withdrawal occurs.
  arm group label: MCLA-129+ Befotertinib
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Shun Lu, M.D.
  role: Study Chair
  affiliation: Shanghai Chest Hospital
  last name: Dandan Zhang, Master
  phone: +86 18626898205
  email: dandan.zhang@bettapharma.com
  facility: 
  contact: 
  contact backup: 
  facility: 
  contact: 
  facility: 
  contact: 
  country: China
  responsible party type: Sponsor
  mesh term: Lung Neoplasms
  mesh term: Carcinoma, Non-Small-Cell Lung
  mesh term: Hypersensitivity
  sharing ipd: No