<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/NCT03758664</url>
  </required_header>
  <id_info>
    <org_study_id>ICP-CL-00301</org_study_id>
    <nct_id>NCT03758664</nct_id>
  </id_info>
  <brief_title>Clinical Study of ICP-192 in Solid Tumors Patients</brief_title>
  <official_title>A Phase I/IIa, Multicenter, Open-Label Study to Assess the Safety, Tolerability, Pharmacokinetics of ICP-192 in Patients With Advanced Solid Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Beijing InnoCare Pharma Tech Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Beijing InnoCare Pharma Tech 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>
      Open-label, non-randomized, Phase I/IIa, dose-escalating, dose-extension, first-in-man study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study consisted of a screening period, a treatment period with 21 days of repeated&#xD;
      treatment per cycle (duration treatment with ICP-192), and a follow-up period (28 days after&#xD;
      last dose). The recruited patients receive a single dose on day 1, then after a 3-day washout&#xD;
      period, repeated dosing will be followed. The starting dose is 2 mg, QD, and dose escalation&#xD;
      will follow accelerated titration and modified 3+3 dose-finding schema. The dose-limiting&#xD;
      toxicity (DLT) assessment period consisted of Cycle 0 (single dose and washout period) and&#xD;
      Cycle 1 (21-day cycle).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 19, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2024</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>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>Adverse events(Phase 1 dose escalation)</measure>
    <time_frame>From the time a signed and dated ICF until 28 days after last dose of study drug</time_frame>
    <description>Adverse events graded by CTCAE V5.0 as a measurement of the safety and tolerability profile of ICP-192</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Objective Response Rate(ORR)(Phase 2a dose expansion)</measure>
    <time_frame>At the end of Cycle 4(each cycle is 21 days)</time_frame>
    <description>Objective response based on assessment of confirmed Complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cmax</measure>
    <time_frame>At the end of Cycle 1(each cycle is 21 days)</time_frame>
    <description>Single dose PK parameters include the peak plasma concentration (Cmax)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC</measure>
    <time_frame>At the end of Cycle 1(each cycle is 21 days)</time_frame>
    <description>Area under the plasma concentration vs. time curve (AUC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent half-life for designated elimination phases (t½)</measure>
    <time_frame>At the end of Cycle 1(each cycle is 21 days)</time_frame>
    <description>will be measured and calculated with noncompartmental analysis using WinNonlin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Food effect</measure>
    <time_frame>Day 1 - 6 after single dose</time_frame>
    <description>ICP-192 concentrations in plasma and urine after dosing in fed and fasted condition</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate(ORR) (Phase 1 dose escalation)</measure>
    <time_frame>At the end of Cycle 4(each cycle is 21 days)</time_frame>
    <description>Objective response based on assessment of confirmed Complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate(DCR)</measure>
    <time_frame>At the end of Cycle 4(each cycle is 21 days)</time_frame>
    <description>DCR based on assessment of confirmed Complete response (CR), partial response (PR) or stable disease(SD) according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Objective Response (DOR)</measure>
    <time_frame>At the end of Cycle 4(each cycle is 21 days)</time_frame>
    <description>Duration of objective response is time interval from the first date that criteria for complete response or partial response are met to the first date of progression of disease</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>At the end of Cycle 4(each cycle is 21 days)</time_frame>
    <description>Progression free survival is the time period from start of study medication till the disease progression or death, whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlationship between FGFR aberrations with efficacy. (Phase 2a dose expansion)</measure>
    <time_frame>At the end of Cycle 4(each cycle is 21 days)</time_frame>
    <description>Correlationship between FGFR mutation/refusion with ORR</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">56</enrollment>
  <condition>Solid Tumor</condition>
  <arm_group>
    <arm_group_label>ICP-192</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The initial dose of ICP-192 is 2 mg, QD, and dose escalation schedule may be modified based on the safety and PK from the previous dose. Tentatively seven dose levels will be evaluated.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ICP-192</intervention_name>
    <description>Drug: ICP-192 Dose levels will be escalated following accelerated titration and modified &quot;3+3&quot; dose escalation scheme,</description>
    <arm_group_label>ICP-192</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. An unresectable or metastatic advanced malignant solid tumor confirmed by&#xD;
             histopathology that has failed to respond to known treatment or has recurred;Subjects&#xD;
             who progress under standard treatment, are intolerant to standard treatment, or do not&#xD;
             have standard treatment (dose escalation phase)&#xD;
&#xD;
          2. Tissue or cell pathology confirmed unresectable, recurrent or metastatic (AJCC version&#xD;
             8 TNM staging IV (2017), biliary tract malignant tumor, or intolerance to first-line&#xD;
             chemotherapy failure (twice (defined as reduction still cannot tolerate) first-line&#xD;
             chemotherapy, neoadjuvant/progress/adjuvant chemotherapy after 6 months recurrence can&#xD;
             be selected (dose extension stage); - At least one evaluable disease according to&#xD;
             RECIST1.1&#xD;
&#xD;
          3. FGFR2 translocation/fusion has been reported or FGFR2 translocation/fusion has been&#xD;
             detected in central laboratory (dose extension phase);&#xD;
&#xD;
          4. Age ≥18 and ≤75&#xD;
&#xD;
          5. There is at least one evaluable lesion according to RECIST1.1 criteria&#xD;
&#xD;
          6. ECOG strength score is 0-1 (dose escalation stage), and ECOG strength score is 0-2&#xD;
             (dose expansion stage).&#xD;
&#xD;
          7. The expected survival time is more than 3 months&#xD;
&#xD;
          8. The organ function level must meet the following requirements (subject to the upper&#xD;
             limit of normal value in the clinical trial center):&#xD;
&#xD;
             A) bone marrow: absolute count of neutrophils (ANC)≥1.5*109/L (1500/mm3), platelet&#xD;
             ≥75*109/L, hemoglobin ≥9g/dL; B) coagulation function: international standardized&#xD;
             ratio of prothrombin time and partial thrombin time &lt;1.5 times the upper limit of&#xD;
             normal value; C) liver: serum bilirubin ≤1.5 times the upper limit of normal value&#xD;
             (tumor involvement in the liver ≤2.5 times the upper limit of normal value), aspartic&#xD;
             aminotransferase (AST) and alanine aminotransferase (ALT)≤3 times the upper limit of&#xD;
             normal value (AST and ALT≤5 times the upper limit of normal value in the case of liver&#xD;
             metastasis); D) serum creatinine ≤1.5 times the upper limit of normal value, or&#xD;
             creatinine clearance ≥70mL/min (calculated according to the Cockroft-gult formula).&#xD;
&#xD;
          9. Volunteer to enroll and sign informed consent to follow the treatment protocol and&#xD;
             visit plan.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous treatment with FGFR small molecule inhibitors or antibody drugs.&#xD;
&#xD;
          -  Anti-cancer therapy, such as chemotherapy (except for oral fluorouracil),&#xD;
             immunotherapy, hormonal, targeted therapy, or investigational agents within four weeks&#xD;
             of the first dose of ICP-192, oral fluorouracil agents within two weeks of the first&#xD;
             dose of ICP-192.&#xD;
&#xD;
          -  Major surgery within 6 weeks of the first dose of ICP-192.&#xD;
&#xD;
          -  Blood phosphate persistently above ULN with intervene therapy within two weeks of the&#xD;
             first dose of ICP-192.&#xD;
&#xD;
          -  Significant GI disorder(s) that could interfere with the absorption, metabolism, or&#xD;
             excretion of ICP-192.&#xD;
&#xD;
          -  Central nervous system (CNS) metastasis&#xD;
&#xD;
          -  Current clinically significant cardiovascular disease including:&#xD;
&#xD;
          -  Any class 3 or 4 cardiac disease such as arrhythmia, congestive heart failure or&#xD;
             myocardial infarction defined by the New York Heart Association Functional&#xD;
             Classification, or left ventricular ejection fraction (LVEF) &lt; 50%, Primary&#xD;
             cardiomyopathy, clinical significant QTc prolong history or QTc&gt;470ms (female)&#xD;
             QTc&gt;450ms (male)&#xD;
&#xD;
          -  Known active bleeding within 2 months of screening or 6 months of bleeding history.&#xD;
&#xD;
          -  According to the investigator's judgement, there are evidences of a serious or&#xD;
             uncontrollable systemic disease (such as unstable or uncompensated respiratory, liver&#xD;
             or kidney disease); or any unstable systemic disease (including active clinically&#xD;
             serious infections, uncontrolled hypertension, liver and kidney or metabolic diseases)&#xD;
&#xD;
          -  History of interstitial pneumonia, deep vein thrombosis, pulmonary embolism. Stroke or&#xD;
             intracranial hemorrhage within 6 months before the first dose of ICP-192.&#xD;
&#xD;
          -  History of organ transplantation and allogeneic hematopoietic stem cell&#xD;
             transplantation.&#xD;
&#xD;
          -  Any corneal or retinal abnormalities that may increase ocular toxicity, including but&#xD;
             not limited to:&#xD;
&#xD;
          -  History of central serous retinopathy (CSR) or retinal vein occlusion (RVO) disease or&#xD;
             has related diseases;&#xD;
&#xD;
          -  Active age-related macular degeneration (AMD);&#xD;
&#xD;
          -  Diabetic retinopathy with macular edema;&#xD;
&#xD;
          -  Uncontrollable glaucoma;&#xD;
&#xD;
          -  Keratonosus, such as Keratitis, keratoconjunctivitis, keratopathy, corneal wear,&#xD;
             inflammation or ulceration.&#xD;
&#xD;
          -  Known active infection with HBV, HCV or HIV or any uncontrolled active systemic&#xD;
             infection&#xD;
&#xD;
          -  Any toxicities must recover to ≤ Grade 1 from prior anti-cancer therapy (excluding&#xD;
             alopecia, nausea and vomiting).&#xD;
&#xD;
          -  Lactating or pregnant women, or women who will not use contraception during the study&#xD;
             and for 180 days after the last dose of study drug if sexually active and able to bear&#xD;
             children.&#xD;
&#xD;
          -  Investigators believe that the patients are not eligible for enrollment for the other&#xD;
             reasons.&#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>Jin Li, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Shanghai East Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jin Li, PhD</last_name>
    <phone>8621-38804518</phone>
    <phone_ext>22132</phone_ext>
    <email>lijin@csco.org.cn</email>
  </overall_contact>
  <location>
    <facility>
      <name>ZhuJiang Hospital of Southern Medical University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510000</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Min Wei Ding</last_name>
      <phone>020-62782364</phone>
      <email>DWM-2001@163.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Henan cancer hospital &amp; Affiliated Tumor Hospital of Zhengzhou University</name>
      <address>
        <city>Zhengzhou</city>
        <state>Henan</state>
        <zip>450008</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Fang Xin Hou</last_name>
      <phone>15136130286</phone>
      <email>zlyyhouxinfang1465@zzu.edu.cn</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hunan cancer hospital &amp; the affiliated cancer hospital of xiangya school of medicine ,central south university</name>
      <address>
        <city>Changsha</city>
        <state>Hunan</state>
        <zip>410006</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Shan Zhi Gu</last_name>
      <phone>0731-89762041</phone>
      <email>gushanzhi@hnszlyy.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>The Second Affiliated Hospital of Soochow University</name>
      <address>
        <city>Suzhou</city>
        <state>Jiangsu</state>
        <zip>215004</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Xiang Zhi Zhuang</last_name>
      <phone>68282030</phone>
      <email>13951106391@139.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>The First Bethune Hospital of Jilin University</name>
      <address>
        <city>Changchun</city>
        <state>Jilin</state>
        <zip>130021</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Wei Li</last_name>
      <phone>0431-88782291</phone>
      <email>jdyylw@163.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Shanghai East Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200120</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jin Li, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Cancer hospital of the university of Chinese academy of sciences</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <zip>310022</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Er Jie Ying</last_name>
      <phone>88122502</phone>
      <email>jieerying01@163.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>November 22, 2018</study_first_submitted>
  <study_first_submitted_qc>November 28, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 29, 2018</study_first_posted>
  <last_update_submitted>July 5, 2022</last_update_submitted>
  <last_update_submitted_qc>July 5, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 6, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>FGFR gene abnormalities</keyword>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03758664
org study id: ICP-CL-00301
nct id: NCT03758664
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Open-label, non-randomized, Phase I/IIa, dose-escalating, dose-extension, first-in-man study.
The study consisted of a screening period, a treatment period with 21 days of repeated
      treatment per cycle (duration treatment with ICP-192), and a follow-up period (28 days after
      last dose). The recruited patients receive a single dose on day 1, then after a 3-day washout
      period, repeated dosing will be followed. The starting dose is 2 mg, QD, and dose escalation
      will follow accelerated titration and modified 3+3 dose-finding schema. The dose-limiting
      toxicity (DLT) assessment period consisted of Cycle 0 (single dose and washout period) and
      Cycle 1 (21-day cycle).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Adverse events(Phase 1 dose escalation)
time frame: From the time a signed and dated ICF until 28 days after last dose of study drug
description: Adverse events graded by CTCAE V5.0 as a measurement of the safety and tolerability profile of ICP-192
measure: Objective Response Rate(ORR)(Phase 2a dose expansion)
time frame: At the end of Cycle 4(each cycle is 21 days)
description: Objective response based on assessment of confirmed Complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST).
measure: Cmax
time frame: At the end of Cycle 1(each cycle is 21 days)
description: Single dose PK parameters include the peak plasma concentration (Cmax)
measure: AUC
time frame: At the end of Cycle 1(each cycle is 21 days)
description: Area under the plasma concentration vs. time curve (AUC)
measure: Apparent half-life for designated elimination phases (t½)
time frame: At the end of Cycle 1(each cycle is 21 days)
description: will be measured and calculated with noncompartmental analysis using WinNonlin
measure: Food effect
time frame: Day 1 - 6 after single dose
description: ICP-192 concentrations in plasma and urine after dosing in fed and fasted condition
measure: Objective Response Rate(ORR) (Phase 1 dose escalation)
time frame: At the end of Cycle 4(each cycle is 21 days)
description: Objective response based on assessment of confirmed Complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST).
measure: Disease control rate(DCR)
time frame: At the end of Cycle 4(each cycle is 21 days)
description: DCR based on assessment of confirmed Complete response (CR), partial response (PR) or stable disease(SD) according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST).
measure: Duration of Objective Response (DOR)
time frame: At the end of Cycle 4(each cycle is 21 days)
description: Duration of objective response is time interval from the first date that criteria for complete response or partial response are met to the first date of progression of disease
measure: Progression Free Survival (PFS)
time frame: At the end of Cycle 4(each cycle is 21 days)
description: Progression free survival is the time period from start of study medication till the disease progression or death, whichever occurs first.
measure: Correlationship between FGFR aberrations with efficacy. (Phase 2a dose expansion)
time frame: At the end of Cycle 4(each cycle is 21 days)
description: Correlationship between FGFR mutation/refusion with ORR
arm group label: ICP-192
arm group type: Experimental
description: The initial dose of ICP-192 is 2 mg, QD, and dose escalation schedule may be modified based on the safety and PK from the previous dose. Tentatively seven dose levels will be evaluated.
intervention type: Drug
intervention name: ICP-192
description: Drug: ICP-192 Dose levels will be escalated following accelerated titration and modified "3+3" dose escalation scheme,
arm group label: ICP-192
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Jin Li, PhD
role: Principal Investigator
affiliation: Shanghai East Hospital
last name: Jin Li, PhD
phone: 8621-38804518
phone ext: 22132
email: lijin@csco.org.cn
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
country: China
responsible party type: Sponsor