<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/NCT04421352</url>
  </required_header>
  <id_info>
    <org_study_id>CS1001-101-13</org_study_id>
    <nct_id>NCT04421352</nct_id>
  </id_info>
  <brief_title>Safety and Tolerability Evaluation of Low-dose Radiation in Combination With CS1001 in Relapsed SCLC Patients</brief_title>
  <official_title>A Phase Ia/Ib, Open-Label, Multiple-Dose, Dose-Escalation and Expansion Study of the Anti-PD-L1 Monoclonal Antibody CS1001 in Subjects With Advanced Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>CStone Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>CStone Pharmaceuticals</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      A Phase Ia/Ib Safety and Tolerability Evaluation of Low-dose Radiation in Combination with&#xD;
      CS1001 in relapsed SCLC patients&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a dose-escalation study of Low-dose Radiation in combination with CS1001 in relapsed&#xD;
      SCLC patients. Patients are assigned to 3 treatment groups received from 3 Gy to 15Gy, to&#xD;
      determine the safety, tolerability and the maximal tolerant dose. Biomarkers and&#xD;
      immunological markers are collected and analyzed as well.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 12, 2021</start_date>
  <completion_date type="Anticipated">October 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</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>To determine the recommended radiation dose and preliminarily evaluate the anti-tumor efficacy of CS1001 in combination with low-dose radiotherapy in subjects with limited or extensive stage SCLC who failed the firstline treatment</measure>
    <time_frame>From date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years.</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of Adverse Events (AE) and Dose-Limiting Toxicity (DLT) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) V4.03</measure>
    <time_frame>From first dose to 30 days after last dose of CS1001, up to 2 years.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax: Peak concentration, the maximum drug concentration measured during one dosing cycle</measure>
    <time_frame>From first dose to 30 days after last dose of CS1001, up to 2 years.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The number and percentage of subjects with detectable Anti-drug Antibody (ADA)</measure>
    <time_frame>From first dose to 30 days after last dose of CS1001, up to 2 years.</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">11</enrollment>
  <condition>Relapsed Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>low-dose radiation+CS1001</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>low-dose radiation+CS1001</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CS1001</intervention_name>
    <description>low-dose radiation+CS1001 1200mg Q3W. In the dose escalation part, the dose levels will be escalated following a modified 3+3 dose escalation scheme.&#xD;
Dose A: 3Gy/1f; Dose B: 9Gy/3f; Dose C: 15Gy/5f;&#xD;
In the dose expansion part, more SCLC patients will be assigned.</description>
    <arm_group_label>low-dose radiation+CS1001</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with histologically or cytologically confirmed LS-SCLC or ES-SCLC and&#xD;
             experienced progression since first-line standard platinum containing dual-drug&#xD;
             chemotherapy.&#xD;
&#xD;
          2. Patients whose initial diagnosis was limited must undergo radical chest radiotherapy&#xD;
             and the time of tumor progression is not less than 3 months from the end of&#xD;
             radiotherapy, or cannot receive radical chest radiotherapy due to specific reasons&#xD;
&#xD;
          3. At least one extracranial measurable lesion (RECIST v1.1), and for a lesion that has&#xD;
             received radiotherapy, progression of the lesion after radiotherapy must be confirmed.&#xD;
&#xD;
          4. Patients with brain metastases are allowed to receive previous radiotherapy and their&#xD;
             condition is stable, but the time to the end of radiotherapy must not be less than 3&#xD;
             months.&#xD;
&#xD;
          5. No radiotherapy contraindications were judged by the radiologist&#xD;
&#xD;
          6. ECOG performance status of 0 or 1.&#xD;
&#xD;
          7. Patients with life expectancy ≥ 3 months.&#xD;
&#xD;
          8. Patients must have adequate organ function.&#xD;
&#xD;
          9. Fertile men and women of childbearing potential must agree to use an effective method&#xD;
             of birth control from providing signed consent and for 6 months after last study drug&#xD;
             administration.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects known to have primary CNS tumors or meningeal metastases or unstable CNS&#xD;
             metastases.&#xD;
&#xD;
          2. Patients with active autoimmune diseases or history of autoimmune diseases should be&#xD;
             excluded.&#xD;
&#xD;
          3. Patients who have received immune checkpoint proteins/antibody/medicine (including&#xD;
             PD-1, PD-L1, etc) for treatment.&#xD;
&#xD;
          4. Known history of HIV infection.&#xD;
&#xD;
          5. Subjects with active chronic hepatitis B or active hepatitis C .&#xD;
&#xD;
          6. Patients who have serious hypersensitive reaction to monoclonal antibodies, and have&#xD;
             history of uncontrolled allergic asthma.&#xD;
&#xD;
          7. Known history of alcoholism or drugs abuse.&#xD;
&#xD;
          8. Subjects with history of radiation pneumonitis of grade 3 or above, regardless of&#xD;
             recovered or not.&#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>You Lu, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>West China Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>West China Hospital, Sichuan University</name>
      <address>
        <city>Chendu</city>
        <state>Sichuan</state>
        <zip>610041</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <results_reference>
    <citation>Horn L, Mansfield AS, Szczesna A, Havel L, Krzakowski M, Hochmair MJ, Huemer F, Losonczy G, Johnson ML, Nishio M, Reck M, Mok T, Lam S, Shames DS, Liu J, Ding B, Lopez-Chavez A, Kabbinavar F, Lin W, Sandler A, Liu SV; IMpower133 Study Group. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N Engl J Med. 2018 Dec 6;379(23):2220-2229. doi: 10.1056/NEJMoa1809064. Epub 2018 Sep 25.</citation>
    <PMID>30280641</PMID>
  </results_reference>
  <results_reference>
    <citation>Ready N, Farago AF, de Braud F, Atmaca A, Hellmann MD, Schneider JG, Spigel DR, Moreno V, Chau I, Hann CL, Eder JP, Steele NL, Pieters A, Fairchild J, Antonia SJ. Third-Line Nivolumab Monotherapy in Recurrent SCLC: CheckMate 032. J Thorac Oncol. 2019 Feb;14(2):237-244. doi: 10.1016/j.jtho.2018.10.003. Epub 2018 Oct 10.</citation>
    <PMID>30316010</PMID>
  </results_reference>
  <results_reference>
    <citation>Li LY, Wang H, Chen X, Li WQ, Cui JW. First-line atezolizumab plus chemotherapy in treatment of extensive small cell lung cancer: a cost-effectiveness analysis from China. Chin Med J (Engl). 2019 Dec 5;132(23):2790-2794. doi: 10.1097/CM9.0000000000000536.</citation>
    <PMID>31856049</PMID>
  </results_reference>
  <results_reference>
    <citation>Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Ozguroglu M, Ji JH, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Kazarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Shire N, Jiang H, Goldman JW; CASPIAN investigators. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1929-1939. doi: 10.1016/S0140-6736(19)32222-6. Epub 2019 Oct 4.</citation>
    <PMID>31590988</PMID>
  </results_reference>
  <results_reference>
    <citation>Yin L, Xue J, Li R, Zhou L, Deng L, Chen L, Zhang Y, Li Y, Zhang X, Xiu W, Tong R, Gong Y, Huang M, Xu Y, Zhu J, Yu M, Li M, Lan J, Wang J, Mo X, Wei Y, Niedermann G, Lu Y. Effect of Low-Dose Radiation Therapy on Abscopal Responses to Hypofractionated Radiation Therapy and Anti-PD1 in Mice and Patients With Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys. 2020 Sep 1;108(1):212-224. doi: 10.1016/j.ijrobp.2020.05.002. Epub 2020 May 15.</citation>
    <PMID>32417411</PMID>
  </results_reference>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>May 29, 2020</study_first_submitted>
  <study_first_submitted_qc>June 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>December 30, 2022</last_update_submitted>
  <last_update_submitted_qc>December 30, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 5, 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>Small Cell Lung Carcinoma</mesh_term>
  </condition_browse>
  <!-- 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/NCT04421352
org study id: CS1001-101-13
nct id: NCT04421352
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: Yes
A Phase Ia/Ib Safety and Tolerability Evaluation of Low-dose Radiation in Combination with
      CS1001 in relapsed SCLC patients
This is a dose-escalation study of Low-dose Radiation in combination with CS1001 in relapsed
      SCLC patients. Patients are assigned to 3 treatment groups received from 3 Gy to 15Gy, to
      determine the safety, tolerability and the maximal tolerant dose. Biomarkers and
      immunological markers are collected and analyzed as well.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: To determine the recommended radiation dose and preliminarily evaluate the anti-tumor efficacy of CS1001 in combination with low-dose radiotherapy in subjects with limited or extensive stage SCLC who failed the firstline treatment
time frame: From date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years.
measure: Incidence of Adverse Events (AE) and Dose-Limiting Toxicity (DLT) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) V4.03
time frame: From first dose to 30 days after last dose of CS1001, up to 2 years.
measure: Cmax: Peak concentration, the maximum drug concentration measured during one dosing cycle
time frame: From first dose to 30 days after last dose of CS1001, up to 2 years.
measure: The number and percentage of subjects with detectable Anti-drug Antibody (ADA)
time frame: From first dose to 30 days after last dose of CS1001, up to 2 years.
arm group label: low-dose radiation+CS1001
arm group type: Experimental
description: low-dose radiation+CS1001
intervention type: Drug
intervention name: CS1001
description: low-dose radiation+CS1001 1200mg Q3W. In the dose escalation part, the dose levels will be escalated following a modified 3+3 dose escalation scheme.
Dose A: 3Gy/1f; Dose B: 9Gy/3f; Dose C: 15Gy/5f;
In the dose expansion part, more SCLC patients will be assigned.
arm group label: low-dose radiation+CS1001
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: You Lu, MD
role: Principal Investigator
affiliation: West China Hospital
facility: 
country: China
citation: Horn L, Mansfield AS, Szczesna A, Havel L, Krzakowski M, Hochmair MJ, Huemer F, Losonczy G, Johnson ML, Nishio M, Reck M, Mok T, Lam S, Shames DS, Liu J, Ding B, Lopez-Chavez A, Kabbinavar F, Lin W, Sandler A, Liu SV; IMpower133 Study Group. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N Engl J Med. 2018 Dec 6;379(23):2220-2229. doi: 10.1056/NEJMoa1809064. Epub 2018 Sep 25.
PMID: 30280641
citation: Ready N, Farago AF, de Braud F, Atmaca A, Hellmann MD, Schneider JG, Spigel DR, Moreno V, Chau I, Hann CL, Eder JP, Steele NL, Pieters A, Fairchild J, Antonia SJ. Third-Line Nivolumab Monotherapy in Recurrent SCLC: CheckMate 032. J Thorac Oncol. 2019 Feb;14(2):237-244. doi: 10.1016/j.jtho.2018.10.003. Epub 2018 Oct 10.
PMID: 30316010
citation: Li LY, Wang H, Chen X, Li WQ, Cui JW. First-line atezolizumab plus chemotherapy in treatment of extensive small cell lung cancer: a cost-effectiveness analysis from China. Chin Med J (Engl). 2019 Dec 5;132(23):2790-2794. doi: 10.1097/CM9.0000000000000536.
PMID: 31856049
citation: Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Ozguroglu M, Ji JH, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Kazarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Shire N, Jiang H, Goldman JW; CASPIAN investigators. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1929-1939. doi: 10.1016/S0140-6736(19)32222-6. Epub 2019 Oct 4.
PMID: 31590988
citation: Yin L, Xue J, Li R, Zhou L, Deng L, Chen L, Zhang Y, Li Y, Zhang X, Xiu W, Tong R, Gong Y, Huang M, Xu Y, Zhu J, Yu M, Li M, Lan J, Wang J, Mo X, Wei Y, Niedermann G, Lu Y. Effect of Low-Dose Radiation Therapy on Abscopal Responses to Hypofractionated Radiation Therapy and Anti-PD1 in Mice and Patients With Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys. 2020 Sep 1;108(1):212-224. doi: 10.1016/j.ijrobp.2020.05.002. Epub 2020 May 15.
PMID: 32417411
responsible party type: Sponsor
mesh term: Small Cell Lung Carcinoma