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/NCT06038396</url>
    </required_header>
    <id_info>
      <org_study_id>RC118-C002</org_study_id>
      <nct_id>NCT06038396</nct_id>
    </id_info>
    <brief_title>A Study of RC118 Plus Toripalimab in Patients With Locally Advanced Unresectable or Metastatic Solid Tumors</brief_title>
    <official_title>An Open, Multi-center Phase I/IIa Clinical Study of RC118 in Combination With Toripalimab for Treatment of Patients With Locally Advanced Unresectable or Metastatic Malignant Solid Tumors With Positive Expression of Claudin 18.2</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>
      <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>
        In Phase I, This study will explore the tolerability and safety of RC118 in combination with&#xD;
        toripalimab for treatment of patients with locally advanced unresectable or metastatic&#xD;
        malignant solid tumors with positive Claudin 18.2 expression, and determine the maximum&#xD;
        tolerated dose (MTD) and the recommended dose in phase II clinical trials (RP2D); In Phase&#xD;
        IIa, to explore the clinical effectiveness and safety of long-term use of RC118 in&#xD;
        combination with toripalimab at RP2D doses for patients with different tumor types.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        this study is an open, single arm, multi-center Phase I /IIa clinical study. In the phase I,&#xD;
        patients with locally advanced unresectable or metastatic malignant solid tumors (gastric&#xD;
        cancer, esophageal cancer, gastroesophageal junction cancer, pancreatic cancer, ovarian&#xD;
        cancer, cholangiocarcinoma, etc.) that are positive for Claudin 18.2(positive membrane&#xD;
        staining observed in any tumor cells) will be included. in Phase I dose escalation phase, 4&#xD;
        dose groups of RC118 will be preset：1.0 mg/kg、1.5 mg/kg、2.0 mg/kg and 2.5 mg/kg, and&#xD;
        toripalimab is fixed dose of 3.0mg/mg; In phase IIa cohort expansion phase, with reference to&#xD;
        the results of the phase I study, subjects were grouped according to different tumor types,&#xD;
        there are at least 20 subjects in each group, initially considering the inclusion of Claudin&#xD;
        18.2 positive (a clear cut-off value will be defined based on the results of Phase I) locally&#xD;
        advanced unresectable or metastatic gastric cancer/gastroesophageal junction cancer, and&#xD;
        other solid tumors (The specific tumor types and groups will be further adjusted based on the&#xD;
        results of the phase I study).&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 3, 2023</start_date>
    <completion_date type="Anticipated">August 31, 2026</completion_date>
    <primary_completion_date type="Anticipated">February 28, 2026</primary_completion_date>
    <phase>Phase 1/Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Dose limiting toxicity (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 RC118 + Toripalimab 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 90 days after the day of the last treatment</time_frame>
      <description>The incidence and severity of adverse events (AE)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Objective 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>
    </primary_outcome>
    <secondary_outcome>
      <measure>Disease Control Rate (DCR)</measure>
      <time_frame>15 months</time_frame>
      <description>Disease Control Rate was defined as the percentage of participants with a complete response (CR) or partial response (PR) or stable disease(SD)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression-free survival (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>Duration of Remission (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>Overall survival (OS)</measure>
      <time_frame>15 months</time_frame>
      <description>Overall survival (OS) (median) was determined using the number of months measured from the initial date of treatment to the date of death.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>RC118 pharmacokinetics: Area under the concentration time curve over the dosing interval.</measure>
      <time_frame>15 months</time_frame>
      <description>RC118 pharmacokinetics: Area under the concentration time curve over the dosing interval.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>RC118 pharmacokinetics: Maximum concentration of the drug (Cmax).</measure>
      <time_frame>15 months</time_frame>
      <description>RC118 pharmacokinetics: Maximum concentration of the drug (Cmax).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>RC118 pharmacokinetics: Time to maximum concentration (Tmax).</measure>
      <time_frame>15 months</time_frame>
      <description>RC118 pharmacokinetics: Time to maximum concentration (Tmax).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>RC118 pharmacokinetics: Elimination half-life (t1/2).</measure>
      <time_frame>15 months</time_frame>
      <description>RC118 pharmacokinetics: Elimination half-life (t1/2).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>RC118 pharmacokinetics: Clearance (CL).</measure>
      <time_frame>15 months</time_frame>
      <description>RC118 pharmacokinetics: Clearance (CL).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>RC118 pharmacokinetics: Mean residence time (MRT).</measure>
      <time_frame>15 months</time_frame>
      <description>RC118 pharmacokinetics: Mean residence time (MRT).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>RC118 pharmacokinetics: Apparent volume of distribution (Vd).</measure>
      <time_frame>15 months</time_frame>
      <description>RC118 pharmacokinetics: Apparent volume of distribution (Vd).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>RC118 pharmacokinetics: Elimination rate constant (λz).</measure>
      <time_frame>15 months</time_frame>
      <description>RC118 pharmacokinetics: Elimination rate constant (λz).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>RC118 immunogenicity: Number of participants with anti-drug-antibody (ADA)</measure>
      <time_frame>15 months</time_frame>
      <description>RC118 immunogenicity: Number of participants with anti-drug-antibody (ADA)</description>
    </secondary_outcome>
    <number_of_arms>6</number_of_arms>
    <enrollment type="Anticipated">64</enrollment>
    <condition>Advanced Solid Tumor</condition>
    <arm_group>
      <arm_group_label>Part A-Arm 1</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Part A will follow the standard 3+3 dose escalation design, 3~6 participants will be allocated to the first dose group of RC118, and receive a treatment of RC118-ADC (1.0mg/kg) and Toripalimab (3.0mg/kg) followed by 14 days of dose limited toxicity (DLT) observation period.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Part A-Arm 2</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Part A will follow the standard 3+3 dose escalation design, 3~6 participants will be allocated to the second dose group of RC118, and receive a treatment of RC118-ADC (1.5mg/kg) and Toripalimab (3.0mg/kg) followed by 14 days of dose limited toxicity (DLT) observation period.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Part A-Arm 3</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Part A will follow the standard 3+3 dose escalation design, 3~6 participants will be allocated to the Thrid dose group of RC118, and receive a treatment of RC118-ADC (2.0mg/kg) and Toripalimab (3.0mg/kg) followed by 14 days of dose limited toxicity (DLT) observation period.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Part A-Arm 4</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Part A will follow the standard 3+3 dose escalation design, 3~6 participants will be allocated to the last dose group of RC118, and receive a treatment of RC118-ADC (2.5mg/kg) and Toripalimab (3.0mg/kg) followed by 14 days of dose limited toxicity (DLT) observation period.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Part B-Arm 1</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Part B-Arm 1 will include approximately 20 patients with gastric cancer (including gastric esophageal junction). This subject group will receive RC118-ADC and Toripalimab (3.0mg/kg) Day 1 of every 14-day cycle. The starting dose of RC118-ADC for expansion will be derived from the RP2D determined during Part A.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Part B-Arm 2</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Part B-Arm 1 will include approximately 20 patients with pancreatic cancer and other solid tumors. This subject group will receive RC118-ADC and Toripalimab (3.0mg/kg) Day 1 of every 14-day cycle. The starting dose of RC118-ADC for expansion will be derived from the RP2D determined during Part A.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>RC118</intervention_name>
      <description>RC118 for injection is a novel antibody-drug conjugate, with a Claudin 18.2-targeting antibody and a microtube inhibitor</description>
      <arm_group_label>Part A-Arm 1</arm_group_label>
      <arm_group_label>Part A-Arm 2</arm_group_label>
      <arm_group_label>Part A-Arm 3</arm_group_label>
      <arm_group_label>Part A-Arm 4</arm_group_label>
      <arm_group_label>Part B-Arm 1</arm_group_label>
      <arm_group_label>Part B-Arm 2</arm_group_label>
      <other_name>RC118 for injection</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Toripalimab</intervention_name>
      <description>Toripalimab is a recombinant humanized anti-PD1 monoclonal antibody</description>
      <arm_group_label>Part A-Arm 1</arm_group_label>
      <arm_group_label>Part A-Arm 2</arm_group_label>
      <arm_group_label>Part A-Arm 3</arm_group_label>
      <arm_group_label>Part A-Arm 4</arm_group_label>
      <arm_group_label>Part B-Arm 1</arm_group_label>
      <arm_group_label>Part B-Arm 2</arm_group_label>
      <other_name>Toripalimab for injection</other_name>
      <other_name>JS001</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Volunteer to participate in this study and sign written informed consent&#xD;
  &#xD;
            -  18 years old ≤ age ≤ 75 years old, no gender limit&#xD;
  &#xD;
            -  ECOG physical status score is 0 or 1 point&#xD;
  &#xD;
            -  The expected survival time exceeds 12 weeks&#xD;
  &#xD;
            -  In dose escalation part, Inclusion locally advanced or metastatic malignant solid&#xD;
               cancer who have previously received at least first-line standard treatment&#xD;
  &#xD;
            -  In dose expansion part, inclusion locally advanced or metastatic gastric cancer who&#xD;
               have previously received first-line standard treatment; And other locally advanced or&#xD;
               metastatic malignant solid cancer who have previously received at least first-line&#xD;
               standard treatment&#xD;
  &#xD;
            -  The subject agrees to provide freshly collected tumor tissue specimens or collected&#xD;
               and preserved tumor tissue specimens within 2 years during the screening period for&#xD;
               CLDN 18.2 testing, and must meet the following criteria： A. Phase I dose escalation&#xD;
               stage/dose confirmation stage: patients with gastric cancer, esophageal cancer,&#xD;
               gastroesophageal junction cancer, pancreatic cancer, ovarian cancer, and&#xD;
               cholangiocarcinoma with positive Claudin 18.2 expression (membrane staining is&#xD;
               observed in any tumor cells); B. Phase IIa study stage: Patients with gastric cancer,&#xD;
               esophageal cancer, gastroesophageal junction cancer, pancreatic cancer, etc. with&#xD;
               positive Claudin 18.2 expression (the cut-off value will be clearly defined based on&#xD;
               the phase I results)&#xD;
  &#xD;
            -  According to the RECIST v1.1 standard, based on imaging examination (CT/MRI), there is&#xD;
               at least one measurable or evaluable target lesion&#xD;
  &#xD;
            -  Sufficient bone marrow, liver, and kidney functions (subject to the normal value of&#xD;
               the clinical trial center): absolute neutrophil count (ANC) ≥ 1.5×109/L, platelet ≥&#xD;
               100×109/L, hemoglobin ≥ 90 g/ L, serum total bilirubin ≤ 1.5 times the upper limit of&#xD;
               normal (ULN), ALT, AST or ALP ≤ 3 times ULN without liver metastasis; ALT, AST or ALP&#xD;
               ≤ 5 times ULN with liver metastasis, serum creatinine ≤ 1.5 Times ULN, International&#xD;
               Normalized Ratio (INR) ≤ 1.5 times ULN, APTT ≤ 1.5 times ULN&#xD;
  &#xD;
            -  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&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Women who are pregnant or breastfeeding, or women whose blood pregnancy test results&#xD;
               are positive during the screening period (female subjects who are infertile do not&#xD;
               need to undergo a pregnancy test, such as hysterectomy and/or bilateral ovaries in the&#xD;
               past Women with resection or amenorrhea ≥12 months)&#xD;
  &#xD;
            -  Subjects with positive test results for hepatitis B surface antigen (HBsAg), hepatitis&#xD;
               C antibody (HCV-Ab), and human immunodeficiency virus antibody (HIV-Ab) during the&#xD;
               screening period&#xD;
  &#xD;
            -  Subjects who have a history of other acquired or congenital immunodeficiency diseases&#xD;
               or organ transplantation&#xD;
  &#xD;
            -  Those who have previously received targeted therapy drugs for Claudin 18.2; or&#xD;
               participated in clinical trials of other drugs within 4 weeks before the first&#xD;
               administration and received trial drugs&#xD;
  &#xD;
            -  Have vaccinated within 4 weeks before the first dose or plan to vaccinate any vaccine&#xD;
               during the study period&#xD;
  &#xD;
            -  People with allergies, or allergic to known research drug ingredients or excipients&#xD;
  &#xD;
            -  Combined use of vitamin K antagonist anticoagulant drugs; combined use of therapeutic&#xD;
               doses of heparin (subjects using preventive doses of heparin can be included in the&#xD;
               study)&#xD;
  &#xD;
            -  Received anti-tumor therapy (surgery, chemotherapy, radiotherapy, biological therapy)&#xD;
               within 4 weeks before the first administration, and received palliative radiotherapy&#xD;
               for bone metastases within 2 weeks&#xD;
  &#xD;
            -  The toxicity of previous anti-tumor treatments has not returned to the level 0 or 1 of&#xD;
               NCI-CTCAE v5.0 (except for hair loss)&#xD;
  &#xD;
            -  There are clinical symptoms of the third space effusion (large amounts of pleural&#xD;
               fluid or ascites) that cannot be controlled by drainage or other methods&#xD;
  &#xD;
            -  According to the judgment of the investigator, an active infection with clinical&#xD;
               significance&#xD;
  &#xD;
            -  Combined with other diseases that seriously endanger the safety of the subject or&#xD;
               affect the completion of the test, such as gastrointestinal bleeding (within 4 weeks&#xD;
               before the first dose), peptic ulcer, intestinal obstruction, intestinal paralysis,&#xD;
               interstitial pneumonia, lung Fibrosis, kidney failure, and uncontrolled diabetes&#xD;
  &#xD;
            -  QTc interval during the screening period&gt;480 ms (based on the average of 3 screening&#xD;
               electrocardiograms); previous family or personal history of long/short QT interval&#xD;
               syndrome; ventricular arrhythmia deemed clinically significant by the investigator&#xD;
               Medical history, or currently receiving antiarrhythmic drug treatment, or implantation&#xD;
               of arrhythmia defibrillation device&#xD;
  &#xD;
            -  Past myocardial infarction (within 6 months before the first administration), severe&#xD;
               or unstable angina, coronary or peripheral artery bypass grafting, New York Heart&#xD;
               Association (NYHA) grade 3~4 heart failure, no Controlled hypertension&#xD;
  &#xD;
            -  People who have had alcohol dependence or drug abuse in the past&#xD;
  &#xD;
            -  Those who have received systemic steroid therapy for a long period of time (Note:&#xD;
               Short-term use (≤ 7 days) and withdrawal&gt; 2 weeks can be selected)&#xD;
  &#xD;
            -  Patients who have previously or currently suffered from uncontrolled primary or&#xD;
               metastatic brain tumors, and the investigator believes that patients who have been&#xD;
               stabilized or whose local treatment has ended may be considered for inclusion in the&#xD;
               group&#xD;
  &#xD;
            -  Past or current peripheral neuropathy ≥ Grade 2&#xD;
  &#xD;
            -  Past or current mental illness that is difficult to control&#xD;
  &#xD;
            -  Past or current mental illness that is difficult to control&#xD;
  &#xD;
            -  Other subjects deemed unsuitable to participate in clinical research by the&#xD;
               investigator&#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>liu.tianshu@zs-hospital.sh.cn Liu, ph.D</last_name>
      <role>Principal Investigator</role>
      <affiliation>Shanghai Zhongshan Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Jianming Fang, ph.D</last_name>
      <phone>+8610-58075763</phone>
      <email>jianmin.fang@remegen.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Tianshu Liu, ph.D</last_name>
      <phone>+86-21-31587871</phone>
      <email>liu.tianshu@zs-hospital.sh.cn</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>hongshan Hospital Affiliated to Fudan University</name>
        <address>
          <city>Shanghai</city>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Tianshu Liu, ph.D</last_name>
        <phone>+86-21-31587871</phone>
        <email>liu.tianshu@zs-hospital.sh.cn</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 1, 2023</study_first_submitted>
    <study_first_submitted_qc>September 7, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 14, 2023</study_first_posted>
    <last_update_submitted>September 14, 2023</last_update_submitted>
    <last_update_submitted_qc>September 14, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 18, 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/NCT06038396
  org study id: RC118-C002
  nct id: NCT06038396
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  In Phase I, This study will explore the tolerability and safety of RC118 in combination with
        toripalimab for treatment of patients with locally advanced unresectable or metastatic
        malignant solid tumors with positive Claudin 18.2 expression, and determine the maximum
        tolerated dose (MTD) and the recommended dose in phase II clinical trials (RP2D); In Phase
        IIa, to explore the clinical effectiveness and safety of long-term use of RC118 in
        combination with toripalimab at RP2D doses for patients with different tumor types.
  this study is an open, single arm, multi-center Phase I /IIa clinical study. In the phase I,
        patients with locally advanced unresectable or metastatic malignant solid tumors (gastric
        cancer, esophageal cancer, gastroesophageal junction cancer, pancreatic cancer, ovarian
        cancer, cholangiocarcinoma, etc.) that are positive for Claudin 18.2(positive membrane
        staining observed in any tumor cells) will be included. in Phase I dose escalation phase, 4
        dose groups of RC118 will be preset：1.0 mg/kg、1.5 mg/kg、2.0 mg/kg and 2.5 mg/kg, and
        toripalimab is fixed dose of 3.0mg/mg; In phase IIa cohort expansion phase, with reference to
        the results of the phase I study, subjects were grouped according to different tumor types,
        there are at least 20 subjects in each group, initially considering the inclusion of Claudin
        18.2 positive (a clear cut-off value will be defined based on the results of Phase I) locally
        advanced unresectable or metastatic gastric cancer/gastroesophageal junction cancer, and
        other solid tumors (The specific tumor types and groups will be further adjusted based on the
        results of the phase I study).
  allocation: Non-Randomized
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Dose limiting toxicity (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 RC118 + Toripalimab treatment
  measure: The incidence and severity of adverse events (AE)
  time frame: From the day of ICF sign to 90 days after the day of the last treatment
  description: The incidence and severity of adverse events (AE)
  measure: Objective 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: Disease Control Rate (DCR)
  time frame: 15 months
  description: Disease Control Rate was defined as the percentage of participants with a complete response (CR) or partial response (PR) or stable disease(SD)
  measure: Progression-free survival (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: Duration of Remission (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: Overall survival (OS)
  time frame: 15 months
  description: Overall survival (OS) (median) was determined using the number of months measured from the initial date of treatment to the date of death.
  measure: RC118 pharmacokinetics: Area under the concentration time curve over the dosing interval.
  time frame: 15 months
  description: RC118 pharmacokinetics: Area under the concentration time curve over the dosing interval.
  measure: RC118 pharmacokinetics: Maximum concentration of the drug (Cmax).
  time frame: 15 months
  description: RC118 pharmacokinetics: Maximum concentration of the drug (Cmax).
  measure: RC118 pharmacokinetics: Time to maximum concentration (Tmax).
  time frame: 15 months
  description: RC118 pharmacokinetics: Time to maximum concentration (Tmax).
  measure: RC118 pharmacokinetics: Elimination half-life (t1/2).
  time frame: 15 months
  description: RC118 pharmacokinetics: Elimination half-life (t1/2).
  measure: RC118 pharmacokinetics: Clearance (CL).
  time frame: 15 months
  description: RC118 pharmacokinetics: Clearance (CL).
  measure: RC118 pharmacokinetics: Mean residence time (MRT).
  time frame: 15 months
  description: RC118 pharmacokinetics: Mean residence time (MRT).
  measure: RC118 pharmacokinetics: Apparent volume of distribution (Vd).
  time frame: 15 months
  description: RC118 pharmacokinetics: Apparent volume of distribution (Vd).
  measure: RC118 pharmacokinetics: Elimination rate constant (λz).
  time frame: 15 months
  description: RC118 pharmacokinetics: Elimination rate constant (λz).
  measure: RC118 immunogenicity: Number of participants with anti-drug-antibody (ADA)
  time frame: 15 months
  description: RC118 immunogenicity: Number of participants with anti-drug-antibody (ADA)
  arm group label: Part A-Arm 1
  arm group type: Experimental
  description: Part A will follow the standard 3+3 dose escalation design, 3~6 participants will be allocated to the first dose group of RC118, and receive a treatment of RC118-ADC (1.0mg/kg) and Toripalimab (3.0mg/kg) followed by 14 days of dose limited toxicity (DLT) observation period.
  arm group label: Part A-Arm 2
  arm group type: Experimental
  description: Part A will follow the standard 3+3 dose escalation design, 3~6 participants will be allocated to the second dose group of RC118, and receive a treatment of RC118-ADC (1.5mg/kg) and Toripalimab (3.0mg/kg) followed by 14 days of dose limited toxicity (DLT) observation period.
  arm group label: Part A-Arm 3
  arm group type: Experimental
  description: Part A will follow the standard 3+3 dose escalation design, 3~6 participants will be allocated to the Thrid dose group of RC118, and receive a treatment of RC118-ADC (2.0mg/kg) and Toripalimab (3.0mg/kg) followed by 14 days of dose limited toxicity (DLT) observation period.
  arm group label: Part A-Arm 4
  arm group type: Experimental
  description: Part A will follow the standard 3+3 dose escalation design, 3~6 participants will be allocated to the last dose group of RC118, and receive a treatment of RC118-ADC (2.5mg/kg) and Toripalimab (3.0mg/kg) followed by 14 days of dose limited toxicity (DLT) observation period.
  arm group label: Part B-Arm 1
  arm group type: Experimental
  description: Part B-Arm 1 will include approximately 20 patients with gastric cancer (including gastric esophageal junction). This subject group will receive RC118-ADC and Toripalimab (3.0mg/kg) Day 1 of every 14-day cycle. The starting dose of RC118-ADC for expansion will be derived from the RP2D determined during Part A.
  arm group label: Part B-Arm 2
  arm group type: Experimental
  description: Part B-Arm 1 will include approximately 20 patients with pancreatic cancer and other solid tumors. This subject group will receive RC118-ADC and Toripalimab (3.0mg/kg) Day 1 of every 14-day cycle. The starting dose of RC118-ADC for expansion will be derived from the RP2D determined during Part A.
  intervention type: Drug
  intervention name: RC118
  description: RC118 for injection is a novel antibody-drug conjugate, with a Claudin 18.2-targeting antibody and a microtube inhibitor
  arm group label: Part A-Arm 1
  arm group label: Part A-Arm 2
  arm group label: Part A-Arm 3
  arm group label: Part A-Arm 4
  arm group label: Part B-Arm 1
  arm group label: Part B-Arm 2
  other name: RC118 for injection
  intervention type: Drug
  intervention name: Toripalimab
  description: Toripalimab is a recombinant humanized anti-PD1 monoclonal antibody
  arm group label: Part A-Arm 1
  arm group label: Part A-Arm 2
  arm group label: Part A-Arm 3
  arm group label: Part A-Arm 4
  arm group label: Part B-Arm 1
  arm group label: Part B-Arm 2
  other name: Toripalimab for injection
  other name: JS001
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: liu.tianshu@zs-hospital.sh.cn Liu, ph.D
  role: Principal Investigator
  affiliation: Shanghai Zhongshan Hospital
  last name: Jianming Fang, ph.D
  phone: +8610-58075763
  email: jianmin.fang@remegen.com
  last name: Tianshu Liu, ph.D
  phone: +86-21-31587871
  email: liu.tianshu@zs-hospital.sh.cn
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Sponsor
  mesh term: Neoplasms
  sharing ipd: No