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/NCT06016062</url>
    </required_header>
    <id_info>
      <org_study_id>RC148-C001</org_study_id>
      <nct_id>NCT06016062</nct_id>
    </id_info>
    <brief_title>A Study of RC148 in Patients With Locally Advanced Unresectable or Metastatic Malignant Solid Tumors</brief_title>
    <official_title>Safety, Tolerability, Pharmacokinetics, and Efficacy of RC148 in Patients With Locally Advanced Unresectable or Metastatic Solid Tumors: an Open-Label, Multicenter, Phase I Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>RemeGen Co., Ltd.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>RemeGen Co., Ltd.</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This trial is to evaluate the safety, tolerability, maximum tolerated dose (MTD) / maximum&#xD;
        administered dose (MAD), pharmacokinetics (PK), pharmacodynamics, immunogenicity and&#xD;
        recommended Phase 2 dose (RP2D) of RC148 in participants with locally advanced unresectable&#xD;
        or metastatic solid tumors.In addition, the preliminary anti-tumour efficacy of RC148 as&#xD;
        single agent will be assessed.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">December 31, 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>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>Maximum tolerated dose(MTD)/Maximum administered dose(MAD)</measure>
      <time_frame>Subjects will be treated and observed for DLT through the end of the first cycle (Days 1-28)</time_frame>
      <description>MTD/MAD based on number of Dose limiting toxicity (DLT)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>DLT</measure>
      <time_frame>28 days after first treatment</time_frame>
      <description>In the DLT evaluation window (observation period 1-28 days after the first administration), according to the NCI-CTCAE v5.0 grading standard, the investigator or the sponsor believes that toxic reaction which are reasonably related to RC148 treatment</description>
    </primary_outcome>
    <primary_outcome>
      <measure>The incidence and severity of adverse events (AE)</measure>
      <time_frame>From the day of ICF sign to 28/90 days after the day of the last treatment</time_frame>
      <description>Adverse events was assessed by investigator(s) according to NCI-CTCAE v5.0</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Recommended Phase 2 dose(RP2D)</measure>
      <time_frame>28 days or 1cycle</time_frame>
      <description>The RP2D may be selected as 1 dose level lower than the MTD and will be determined in discussion with the safety monitoring committee based on all available data</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Antitumor Activity of RC148 by Overall Response Rate(ORR)</measure>
      <time_frame>15 months</time_frame>
      <description>Objective Response Rate was defined as the percentage of participants with a complete response (CR) or partial response (PR)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>DCR</measure>
      <time_frame>15 months</time_frame>
      <description>Disease Control Rate was defined as the percentage of participants with a CR or PR or stable disease(SD)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>DOR</measure>
      <time_frame>15 months</time_frame>
      <description>Duration of response is the length of time that a tumor continues to respond to treatment without the cancer growing or spreading</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PFS</measure>
      <time_frame>15 months</time_frame>
      <description>Progression-free Survival (PFS) (median) was determined using the number of months measured from the initial date of treatment to the date of documented progression, or the date of death (in the absence of progression) of participants. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics (PK) parameter: Maximum concentration (Cmax)</measure>
      <time_frame>15 months</time_frame>
      <description>Cmax will be derived from the PK blood samples collected.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PK parameter: Time to maximum concentration (Tmax)</measure>
      <time_frame>15 months</time_frame>
      <description>Tmax will be derived from the PK blood samples collecte</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PK parameter: Terminal or apparent terminal half-life (t1/2)</measure>
      <time_frame>15 months</time_frame>
      <description>t1/2 will be derived from the PK blood samples collected.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PK parameter: Area under the concentration-time curve (AUC)</measure>
      <time_frame>15 months</time_frame>
      <description>AUC will be derived from the PK blood samples collected.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PK parameter:Systemic clearance (CL)</measure>
      <time_frame>15 months</time_frame>
      <description>CL will be derived from the PK blood samples collected.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PK parameter: Mean residence time (MRT)</measure>
      <time_frame>15 months</time_frame>
      <description>MRT will be derived from the PK blood samples collected.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PK parameter: Vz</measure>
      <time_frame>15 months</time_frame>
      <description>Vz will be derived from the PK blood samples collected.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PK parameter: λz</measure>
      <time_frame>15 months</time_frame>
      <description>λz will be derived from the PK blood samples collected.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Immunogenicity assessment</measure>
      <time_frame>15 months</time_frame>
      <description>blood samples will be collected to test the presence anti-RC148 antibodies</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">25</enrollment>
    <condition>Solid Tumor</condition>
    <arm_group>
      <arm_group_label>RC148</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will be allocated to one of the following dose groups:1.0, 3.0, 10.0, 20.0, and 30.0mg/kg, and receive a treatment of RC148 followed by 28 days of dose limited toxicity (DLT) observation period.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>RC148</intervention_name>
      <description>RC148 is a bispecific antibody, targeting programmed death-1(PD-1) and Vascular endothelial growth factor(VEGF).</description>
      <arm_group_label>RC148</arm_group_label>
      <other_name>RC148 for injection</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Participant must be able to provide documented voluntary informed consent.&#xD;
  &#xD;
            2. Male or female participants ≥ 18 years.&#xD;
  &#xD;
            3. Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1.&#xD;
  &#xD;
            4. The expected survival period exceeds 12 weeks.&#xD;
  &#xD;
            5. At least one target lesion that can be measured per Response Evaluation Criteria in&#xD;
               Solid Tumours (RECIST) v1.1.&#xD;
  &#xD;
            6. Histologically or cytologically documented advanced or metastatic solid tumor that is&#xD;
               refractory/relapsed to standard therapies, or for which no effective standard therapy&#xD;
               is available, or the subject refuses standard therapy.&#xD;
  &#xD;
            7. Participants agree to provide pre-treatment archived /biopsy tumour samples (8-10&#xD;
               tissue slides) for retrospective programmed cell death protein 1 (PD-1) related tests.&#xD;
               Archival tumour tissue should be from the most recent timepoint before entering the&#xD;
               trial. Only when archived samples cannot be obtained, the biopsy will be considered at&#xD;
               screening. Fresh tumour biopsies will NOT be considered if significant risk procedures&#xD;
               are required per the discretion of the Investigator.&#xD;
  &#xD;
            8. Adequate bone marrow, liver, and renal function defined as:&#xD;
  &#xD;
                 -  absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L,&#xD;
  &#xD;
                 -  platelet ≥ 100 × 10^9/L,&#xD;
  &#xD;
                 -  haemoglobin ≥ 90 g/L,&#xD;
  &#xD;
                 -  serum total bilirubin ≤ 1.5 × upper limit of normal (ULN),&#xD;
  &#xD;
                 -  ALT, AST ≤ 2.5 × ULN (≤ 5 × ULN when there is known liver metastasis),&#xD;
  &#xD;
                 -  serum creatinine ≤ 1.5 × ULN,&#xD;
  &#xD;
                 -  International normalized ratio (INR) ≤ 1.5 × ULN,&#xD;
  &#xD;
                 -  Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.&#xD;
  &#xD;
            9. Male or female subjects with fertility must agree to take effective contraceptive&#xD;
               measures during the study period and within 6 months after the end of the last&#xD;
               medication, such as double-barrier contraceptive methods, condoms, oral or injectable&#xD;
               contraceptives, intrauterine contraceptive device.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Pregnant or lactating.&#xD;
  &#xD;
            2. Diagnosed active hepatitis B infection (defined as positive of hepatitis B surface&#xD;
               antigen (HBsAg) and hepatitis B deoxyribonucleic acid [DNA]≥500IU/ml), active&#xD;
               hepatitis C infection (defined as presence of hepatitis C ribonucleic acid [RNA]), and&#xD;
               human immunodeficiency virus (HIV) infection (defined as positive HIV test) during the&#xD;
               screening period.&#xD;
  &#xD;
            3. Received live attenuated vaccination within 30 days prior to the first dose of RC148&#xD;
  &#xD;
            4. Participant with a history of other acquired/congenital immunodeficiency diseases or&#xD;
               organ transplantation.&#xD;
  &#xD;
            5. Participant who received prior anti-PD-1, anti- programmed cell death protein ligand 1&#xD;
               (anti-PD-L1), anti-cytotoxic T lymphocyte-associated (CTLA)-4 or any other&#xD;
               immunotherapy or immune-oncology agent within 28 days of commencing treatment with&#xD;
               RC148 or experienced a toxicity that led to permanent discontinuation of prior&#xD;
               immunotherapy.&#xD;
  &#xD;
            6. Participant who had participated in other clinical trials and received study drug&#xD;
               within 4 weeks before the first administration of IP.&#xD;
  &#xD;
            7. Allergic constitution or allergic to known research drug active ingredients or&#xD;
               excipient.&#xD;
  &#xD;
            8. Participant who are under the treatment of anticoagulant drugs (e.g., warfarin,&#xD;
               apixaban, and heparin). Participants using prophylactic doses of heparin (e.g.,&#xD;
               low-molecular-weight heparins [LMWH]) are eligible in the study.&#xD;
  &#xD;
            9. Participant undergo any anti-tumour therapy, including surgery, chemotherapy,&#xD;
               radiotherapy and biological therapy within 4 weeks prior to the first administration&#xD;
               of IP, or palliative radiotherapy for bone/other solitary metastases within 2 weeks&#xD;
               prior to the first administration of IP.&#xD;
  &#xD;
           10. Previous adverse reactions resulting from previous anti-tumour therapies, which have&#xD;
               not returned to Grade 0 or 1 according to NCI-CTCAE v5.0 (except alopecia) at&#xD;
               screening.&#xD;
  &#xD;
           11. There are clinical symptoms of fluid in the third space (e.g., large amounts of&#xD;
               pleural fluid or ascites) that cannot be controlled by drainage or other therapies.&#xD;
  &#xD;
           12. A clinically significant active infection judged by the investigator.&#xD;
  &#xD;
           13. Comorbidities that may seriously endanger the participant's safety or affect the&#xD;
               completion of the study, such as gastrointestinal bleeding (within 4 weeks prior to&#xD;
               the screening period), peptic ulcer (within 4 weeks prior to the screening period),&#xD;
               intestinal obstruction, intestinal paralysis, interstitial pneumonia, pulmonary&#xD;
               fibrosis, kidney failure, and uncontrolled diabetes.&#xD;
  &#xD;
           14. QT interval corrected by Fridericia's formula (QTcF) interval &gt; 480 ms in both male&#xD;
               and female (based on the mean value of the triplicate screening electrocardiogram&#xD;
               [ECG]); family or personal history of long/short QT syndrome; history of ventricular&#xD;
               arrhythmia deemed clinically significant by the investigator, or currently receiving&#xD;
               antiarrhythmic drug treatment, or implantation of arrhythmia defibrillation device.&#xD;
  &#xD;
           15. Have experienced arterial/venous thromboembolic events, such as cerebrovascular&#xD;
               accident (including transient ischemic attack), deep vein thrombosis and pulmonary&#xD;
               embolism within 1 year prior to the initiation of study treatment;&#xD;
  &#xD;
           16. History of myocardial infarction within 6 months prior to the screening period, severe&#xD;
               or unstable angina pectoris, coronary or peripheral artery bypass grafting, heart&#xD;
               failure ≥ 3 (New York Heart Association), or uncontrolled hypertension.&#xD;
  &#xD;
           17. Participants with a condition requiring systemic treatment with either corticosteroid&#xD;
               (&gt; 10 mg daily) or other immunosuppressive medications within 2 weeks of first IP&#xD;
               administration.&#xD;
  &#xD;
           18. Participants with active central nervous system (CNS) metastases. Participants with&#xD;
               treated CNS metastases are permitted on study if the CNS metastases have been&#xD;
               clinically stable for at least 4 weeks prior to treatment initiation and baseline&#xD;
               scans show no evidence of new or enlarged lesions and meanwhile participant does not&#xD;
               have leptomeningeal disease.&#xD;
  &#xD;
           19. Have undergone major surgeries within 4 weeks prior to study treatment and have not&#xD;
               recovered yet;&#xD;
  &#xD;
           20. History or presence of uncontrolled mental illness at the discretion of the&#xD;
               Investigator, which may place the participant at increased risk of safety/tolerability&#xD;
               issues.&#xD;
  &#xD;
           21. The participant is, in the opinion of the investigator, expected to be non-compliant&#xD;
               with critical trial procedures and is not willing or able to adhere to the trial&#xD;
               requirements in the future.&#xD;
  &#xD;
           22. Participants who are not appropriate for this clinical trial at the discretion of the&#xD;
               investigator.&#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>Jianming Fang, ph.D</last_name>
      <phone>+8610-58075763</phone>
      <email>jianmingfang@hotmail.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Henan Cancer Hospital</name>
        <address>
          <city>Zhengzhou</city>
          <state>Henan</state>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Suxia Luo</last_name>
      </contact>
      <investigator>
        <last_name>Suxia Luo</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Shandong Tumor Hospital</name>
        <address>
          <city>Jinan</city>
          <state>Shandong</state>
          <zip>250117</zip>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Jinming Yu, ph.D</last_name>
        <phone>0531-67626971</phone>
      </contact>
      <investigator>
        <last_name>Jinming Yu, ph.D</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Jinan Central Hospital</name>
        <address>
          <city>Jinan</city>
          <state>Shandong</state>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Meili Sun</last_name>
      </contact>
      <investigator>
        <last_name>Meili Sun</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 18, 2023</study_first_submitted>
    <study_first_submitted_qc>August 24, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 29, 2023</study_first_posted>
    <last_update_submitted>August 24, 2023</last_update_submitted>
    <last_update_submitted_qc>August 24, 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>Neoplasms</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/NCT06016062
  org study id: RC148-C001
  nct id: NCT06016062
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  This trial is to evaluate the safety, tolerability, maximum tolerated dose (MTD) / maximum
        administered dose (MAD), pharmacokinetics (PK), pharmacodynamics, immunogenicity and
        recommended Phase 2 dose (RP2D) of RC148 in participants with locally advanced unresectable
        or metastatic solid tumors.In addition, the preliminary anti-tumour efficacy of RC148 as
        single agent will be assessed.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Maximum tolerated dose(MTD)/Maximum administered dose(MAD)
  time frame: Subjects will be treated and observed for DLT through the end of the first cycle (Days 1-28)
  description: MTD/MAD based on number of Dose limiting toxicity (DLT)
  measure: DLT
  time frame: 28 days after first treatment
  description: In the DLT evaluation window (observation period 1-28 days after the first administration), according to the NCI-CTCAE v5.0 grading standard, the investigator or the sponsor believes that toxic reaction which are reasonably related to RC148 treatment
  measure: The incidence and severity of adverse events (AE)
  time frame: From the day of ICF sign to 28/90 days after the day of the last treatment
  description: Adverse events was assessed by investigator(s) according to NCI-CTCAE v5.0
  measure: Recommended Phase 2 dose(RP2D)
  time frame: 28 days or 1cycle
  description: The RP2D may be selected as 1 dose level lower than the MTD and will be determined in discussion with the safety monitoring committee based on all available data
  measure: Antitumor Activity of RC148 by Overall Response Rate(ORR)
  time frame: 15 months
  description: Objective Response Rate was defined as the percentage of participants with a complete response (CR) or partial response (PR)
  measure: DCR
  time frame: 15 months
  description: Disease Control Rate was defined as the percentage of participants with a CR or PR or stable disease(SD)
  measure: DOR
  time frame: 15 months
  description: Duration of response is the length of time that a tumor continues to respond to treatment without the cancer growing or spreading
  measure: PFS
  time frame: 15 months
  description: Progression-free Survival (PFS) (median) was determined using the number of months measured from the initial date of treatment to the date of documented progression, or the date of death (in the absence of progression) of participants. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
  measure: Pharmacokinetics (PK) parameter: Maximum concentration (Cmax)
  time frame: 15 months
  description: Cmax will be derived from the PK blood samples collected.
  measure: PK parameter: Time to maximum concentration (Tmax)
  time frame: 15 months
  description: Tmax will be derived from the PK blood samples collecte
  measure: PK parameter: Terminal or apparent terminal half-life (t1/2)
  time frame: 15 months
  description: t1/2 will be derived from the PK blood samples collected.
  measure: PK parameter: Area under the concentration-time curve (AUC)
  time frame: 15 months
  description: AUC will be derived from the PK blood samples collected.
  measure: PK parameter:Systemic clearance (CL)
  time frame: 15 months
  description: CL will be derived from the PK blood samples collected.
  measure: PK parameter: Mean residence time (MRT)
  time frame: 15 months
  description: MRT will be derived from the PK blood samples collected.
  measure: PK parameter: Vz
  time frame: 15 months
  description: Vz will be derived from the PK blood samples collected.
  measure: PK parameter: λz
  time frame: 15 months
  description: λz will be derived from the PK blood samples collected.
  measure: Immunogenicity assessment
  time frame: 15 months
  description: blood samples will be collected to test the presence anti-RC148 antibodies
  arm group label: RC148
  arm group type: Experimental
  description: Participants will be allocated to one of the following dose groups:1.0, 3.0, 10.0, 20.0, and 30.0mg/kg, and receive a treatment of RC148 followed by 28 days of dose limited toxicity (DLT) observation period.
  intervention type: Drug
  intervention name: RC148
  description: RC148 is a bispecific antibody, targeting programmed death-1(PD-1) and Vascular endothelial growth factor(VEGF).
  arm group label: RC148
  other name: RC148 for injection
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Jianming Fang, ph.D
  phone: +8610-58075763
  email: jianmingfang@hotmail.com
  facility: 
  contact: 
  investigator: 
  facility: 
  contact: 
  investigator: 
  facility: 
  contact: 
  investigator: 
  country: China
  responsible party type: Sponsor
  mesh term: Neoplasms
  sharing ipd: No