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/NCT06015048</url>
    </required_header>
    <id_info>
      <org_study_id>SHR-A1811-208</org_study_id>
      <nct_id>NCT06015048</nct_id>
    </id_info>
    <brief_title>A Trial of SHR-A1811 Combined With Other Antitumor Therapies in Advanced Solid Tumors.</brief_title>
    <official_title>A Phase 1b/2 Study to Evaluate the Safety, Tolerability and Efficacy of SHR-A1811 Combined With Other Antitumor Therapies in Advanced Solid Tumors.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Jiangsu HengRui Medicine Co., Ltd.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Jiangsu HengRui Medicine 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>
        The study is being conducted to evaluate the safety, tolerability and efficacy of SHR-A1811&#xD;
        combined with other antitumor therapies in advanced solid tumors. To explore the reasonable&#xD;
        dosage of SHR-A1811 combined with other antitumor therapies for advanced solid tumors.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">December 29, 2026</completion_date>
    <primary_completion_date type="Anticipated">December 17, 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>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Part A: Maximally Tolerated Dose (MTD)(Phase ⅠB).</measure>
      <time_frame>From the first dose to the last dose, about 11 months</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part A: recommended phase 2 dose (RP2D)(Phase ⅠB).</measure>
      <time_frame>From the first dose to the last dose, about 11 months</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part A: Adverse Events(Phase ⅠB).</measure>
      <time_frame>From the first dose to the last dose, about 11 months</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part A: Objective Response Rate (ORR) (Phase Ⅱ).</measure>
      <time_frame>From the first dose to the last dose, about 11 months</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Part A: ORR (Phase ⅠB).</measure>
      <time_frame>From the first dose to the last dose, about 11 months.</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A: Disease Control Rate (DCR) (Phase ⅠB and Phase Ⅱ)).</measure>
      <time_frame>From the first dose to the last dose, about 11 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A: Duration of Response (DoR) (Phase ⅠB and Phase Ⅱ)</measure>
      <time_frame>From the first dose to the last dose, about 11 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A: Progression-free survival (PFS) (Phase ⅠB and Phase Ⅱ)</measure>
      <time_frame>From the first dose to the last dose, about 13 months.</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A: Overall survival (OS) (Phase ⅠB and Phase Ⅱ)</measure>
      <time_frame>From the first dose to the last dose, about 13 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A: Adverse Events (PhaseⅡ).</measure>
      <time_frame>about 11 months.</time_frame>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">280</enrollment>
    <condition>HER2-expressing Advanced Solid Tumors</condition>
    <arm_group>
      <arm_group_label>Part A: Intervention: Drug: SHR-A1811 combined with Pyrotinib</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Part B1: Intervention: Drug: SHR-A1811 combined with other antitumor therapies</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>SHR-A1811 combined with Pyrotinib.</intervention_name>
      <description>SHR-A1811 combined with Pyrotinib</description>
      <arm_group_label>Part A: Intervention: Drug: SHR-A1811 combined with Pyrotinib</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>SHR-A1811 combined with other antitumor therapies</intervention_name>
      <description>SHR-A1811 combined with other antitumor therapies</description>
      <arm_group_label>Part B1: Intervention: Drug: SHR-A1811 combined with other antitumor therapies</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Able and willing to provide a written informed consent. Have good compliance and&#xD;
               cooperated with follow-up visits.&#xD;
  &#xD;
            2. Subjects are older than or equal to 18 years old and younger than or equal to 75 years&#xD;
               old on the day of signing the informed consent. Male or female.&#xD;
  &#xD;
            3. ECOG score 0-1.&#xD;
  &#xD;
            4. Life expectancy is at least 12 weeks.&#xD;
  &#xD;
            5. Histologically or cytologically confirmed metastatic or advanced unresectable&#xD;
               HER2-expression solid tumors.&#xD;
  &#xD;
            6. Provide ≥ 6 sections of formalin-fixed, paraffin-embedded tumor tissue blocks or&#xD;
               unstained tumor specimen sections. Sections should be archived within 1 year before&#xD;
               the first study treatment or freshly obtained (freshly obtained is preferred).&#xD;
  &#xD;
            7. ≥1 Measurable lesions, according to the Response Evaluation Criteria for Solid Tumors&#xD;
               (RECIST) version 1.1.&#xD;
  &#xD;
            8. Organ function met criteria within 7 days prior to initial administration (No blood&#xD;
               component or cell growth factor was used within 14 days before the initial&#xD;
               administration):&#xD;
  &#xD;
            9. Left ventricular ejection fraction (LVEF) ≥ 50% at baseline within 28 days prior to&#xD;
               initial administration.&#xD;
  &#xD;
           10. Males and women of childbearing age must use reliable contraception from the written&#xD;
               informed consent to 7 months after last drug administration (SHR-A1811) or 8 weeks&#xD;
               after last drug administration (Pyrotinib) or 6 months after last drug administration&#xD;
               (BP102 or Oxaliplatin or Capecitabine), the latest time should be taken as final.&#xD;
               Women of childbearing age must have had a pregnancy test (serum or urine) with&#xD;
               negative results within 7 days prior to initial administration and must not in&#xD;
               lactation period.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Subjects with untreated or known active CNS metastasis. Subjects with a history of&#xD;
               meningeal metastasis or known active meningeal metastasis.&#xD;
  &#xD;
            2. Have a history of antibody drug conjugate with following characteristics:&#xD;
               topoisomerase I inhibitors, including Enhertu (DS-8201a), U3-1402, etc. Part A: Have a&#xD;
               history of Her-2 targeted tyrosine-kinase inhibitor (TKI). Have used strong inhibitor,&#xD;
               moderate inhibitor, strong inducer, or moderate inducer of CYP3A4 within less than 3&#xD;
               half-lives or less than 14 days before the first administration of Pyrotinib (take the&#xD;
               shorter time).&#xD;
  &#xD;
            3. Palliative radiotherapy within 14 days prior to initial administration. Subjects who&#xD;
               had received systemic anti-tumor therapy within 4 weeks prior to initial&#xD;
               administration will not permitted. The interval between the end of small-molecule&#xD;
               targeted drugs administration and initial test drug administration must be ≥ 5&#xD;
               half-lives or 7 days (take the longer time). The interval between the end of Chinese&#xD;
               patent anti-tumor drug administration and initial test drug administration must be ≥ 2&#xD;
               weeks. Participating in another clinical study of other drugs. The interval between&#xD;
               the previous clinical study drug use and this study initial administration is less&#xD;
               than 4 weeks or 5 half-lives of previous clinical study drug (take the shorter time).&#xD;
  &#xD;
            4. Toxicity and/or complications of previous interventions were not recovered to&#xD;
               NCI-CTCAE ≤ grade 1 or didn't meet this inclusion criteria and exclusion criteria. If&#xD;
               investigator determines that the toxicity and/or complications are NCI-CTCAE ≤ grade 2&#xD;
               and there is no safety risk, this subject can be enrolled. For example, patients with&#xD;
               type 1 diabetes or hypothyroidism who have been treated with immune checkpoint&#xD;
               inhibitors and are stable after hormone replacement therapy.&#xD;
  &#xD;
            5. Have a history of (non-infectious) interstitial lung disease (ILD). Suspected ILD.&#xD;
               Other moderate and severe lung diseases that may interfere the detection or management&#xD;
               of drug-related pulmonary toxicity and severely affect respiratory function within 3&#xD;
               months before the first test drug administration. Any autoimmune disease, connective&#xD;
               tissue disease, or inflammatory disease with lung involvement.&#xD;
  &#xD;
            6. Patients unable to swallow orally administered medication and other disorders likely&#xD;
               to interfere the absorption of the study drugs within 28 days before the first test&#xD;
               drug administration.&#xD;
  &#xD;
            7. Patients with moderate and severe ascites of clinical symptoms Refractory or moderate&#xD;
               to severe pleural effusion or pericardial effusion.&#xD;
  &#xD;
            8. Patients with intestinal obstruction within 6 months prior to the first test drug&#xD;
               administration (patients can be enrolled if surgical treatment had been performed and&#xD;
               the obstruction had been completely resolved).&#xD;
  &#xD;
            9. Have clinically significant cardiovascular disease.&#xD;
  &#xD;
           10. Previous or combined with other malignancies except those have achieved complete&#xD;
               remission and do not require or are not expected to require other treatment during the&#xD;
               study period within at least 5 years prior to screening, including basal cell&#xD;
               carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the&#xD;
               skin, cervical carcinoma in situ, local prostate cancer, ductal carcinoma in situ&#xD;
               after radical surgery, etc (hormone therapy for non-metastatic prostate cancer or&#xD;
               breast cancer is allowed) .&#xD;
  &#xD;
           11. Serious infections within 28 days prior to the first test drug administration. Active&#xD;
               infections that had received therapeutic intravenous antibiotics within 2 weeks prior&#xD;
               to the first test drug administration. Prophylactic antibiotic therapy can be&#xD;
               enrolled.&#xD;
  &#xD;
           12. Active hepatitis B or active hepatitis C infection. Active hepatitis B is defined as&#xD;
               hepatitis B surface antigen (HBsAg) positive and HBV-DNA ≥10000 copies/ml [2000 IU/ml]&#xD;
               during screening. Active hepatitis C is defined as hepatitis C virus antibody positive&#xD;
               and HCV-RNA positive during screening. Patients with active pulmonary tuberculosis&#xD;
               infection within 1 year before enrolment, or with a history of active pulmonary&#xD;
               tuberculosis infection but without regular treatment more than 1 year before&#xD;
               enrolment. Has known immunodeficiency disorders, including human immunodeficiency&#xD;
               virus (HIV) infection, etc. Received attenuated live vaccines within 28 days of&#xD;
               initial administration. Expected use of attenuated live vaccines during the study&#xD;
               period.&#xD;
  &#xD;
           13. Major surgery history other than diagnostic or biopsy surgery within 28 days prior to&#xD;
               initial administration. Minor traumatic surgery within 7 days prior to initial&#xD;
               administration. Non-healing wounds. Untreated bone fractures.&#xD;
  &#xD;
           14. Known allergy to any component of SHR-A1811. History of severe allergic reactions to&#xD;
               other monoclonal antibody/fusion protein drugs. Part A: known allergy to any component&#xD;
               of Pyrotinib.&#xD;
  &#xD;
           15. Female subjects who are pregnant, in lactation period, or planning pregnancy during&#xD;
               the study period.&#xD;
  &#xD;
           16. Uncontrolled mental illness and other conditions which will affect the completion of&#xD;
               the study, such as alcohol abuse, drug or substance abuse, criminal detention, etc.&#xD;
  &#xD;
           17. Any other conditions that may not eligible to participate in this study according to&#xD;
               researchers' judgment.&#xD;
  &#xD;
          For Part B1, subjects must not meet any of the following supplementary criteria at the same&#xD;
          time, otherwise they will not be enrolled in the study:&#xD;
  &#xD;
            1. Bleeding tendency, coagulation dysfunction, or high risk of thrombosis.&#xD;
  &#xD;
            2. Poorly controlled hypertension after medication (systolic blood pressure ≥ 140 mmHg&#xD;
               and/or diastolic blood pressure ≥ 90 mmHg in the case of regular anti-hypertensive&#xD;
               therapy) and prior hypertensive crisis or hypertensive encephalopathy. Severe&#xD;
               cerebrovascular diseases and clinically significant vascular diseases.&#xD;
  &#xD;
            3. Known contraindication or allergy to any component of BP102, Oxaliplatin, and&#xD;
               Capecitabine.&#xD;
  &#xD;
            4. Previous treatment with antiangiogenic drug.&#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_contact>
      <last_name>Zhengjin Zhang</last_name>
      <phone>+0518-82342973</phone>
      <email>zhengjin.zhang.zz79@hengrui.com</email>
    </overall_contact>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>August 1, 2023</study_first_submitted>
    <study_first_submitted_qc>August 28, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 29, 2023</study_first_posted>
    <last_update_submitted>August 28, 2023</last_update_submitted>
    <last_update_submitted_qc>August 28, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 29, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Neoplasms</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Undecided</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/NCT06015048
  org study id: SHR-A1811-208
  nct id: NCT06015048
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  The study is being conducted to evaluate the safety, tolerability and efficacy of SHR-A1811
        combined with other antitumor therapies in advanced solid tumors. To explore the reasonable
        dosage of SHR-A1811 combined with other antitumor therapies for advanced solid tumors.
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Part A: Maximally Tolerated Dose (MTD)(Phase ⅠB).
  time frame: From the first dose to the last dose, about 11 months
  measure: Part A: recommended phase 2 dose (RP2D)(Phase ⅠB).
  time frame: From the first dose to the last dose, about 11 months
  measure: Part A: Adverse Events(Phase ⅠB).
  time frame: From the first dose to the last dose, about 11 months
  measure: Part A: Objective Response Rate (ORR) (Phase Ⅱ).
  time frame: From the first dose to the last dose, about 11 months
  measure: Part A: ORR (Phase ⅠB).
  time frame: From the first dose to the last dose, about 11 months.
  measure: Part A: Disease Control Rate (DCR) (Phase ⅠB and Phase Ⅱ)).
  time frame: From the first dose to the last dose, about 11 months
  measure: Part A: Duration of Response (DoR) (Phase ⅠB and Phase Ⅱ)
  time frame: From the first dose to the last dose, about 11 months
  measure: Part A: Progression-free survival (PFS) (Phase ⅠB and Phase Ⅱ)
  time frame: From the first dose to the last dose, about 13 months.
  measure: Part A: Overall survival (OS) (Phase ⅠB and Phase Ⅱ)
  time frame: From the first dose to the last dose, about 13 months
  measure: Part A: Adverse Events (PhaseⅡ).
  time frame: about 11 months.
  arm group label: Part A: Intervention: Drug: SHR-A1811 combined with Pyrotinib
  arm group type: Experimental
  arm group label: Part B1: Intervention: Drug: SHR-A1811 combined with other antitumor therapies
  arm group type: Experimental
  intervention type: Drug
  intervention name: SHR-A1811 combined with Pyrotinib.
  description: SHR-A1811 combined with Pyrotinib
  arm group label: Part A: Intervention: Drug: SHR-A1811 combined with Pyrotinib
  intervention type: Drug
  intervention name: SHR-A1811 combined with other antitumor therapies
  description: SHR-A1811 combined with other antitumor therapies
  arm group label: Part B1: Intervention: Drug: SHR-A1811 combined with other antitumor therapies
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Zhengjin Zhang
  phone: +0518-82342973
  email: zhengjin.zhang.zz79@hengrui.com
  responsible party type: Sponsor
  mesh term: Neoplasms
  sharing ipd: Undecided