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/NCT06008054</url>
    </required_header>
    <id_info>
      <org_study_id>BL-B01D1-SI-B003-201-05</org_study_id>
      <nct_id>NCT06008054</nct_id>
    </id_info>
    <brief_title>A Study of SI-B003 and BL-B01D1+SI-B003 in the Treatment of Patients With Locally Advanced or Metastatic Esophageal Cancer, Gastric Cancer, Colorectal Cancer and Other Gastrointestinal Tumors</brief_title>
    <official_title>A Phase II Clinical Study to Evaluate the Efficacy and Safety of SI-B003 Alone and BL-B01D1+SI-B003 in the Treatment of Patients With Locally Advanced or Metastatic Esophageal Cancer, Gastric Cancer, Colorectal Cancer and Other Gastrointestinal Tumors</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Sichuan Baili Pharmaceutical Co., Ltd.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Sichuan Baili Pharmaceutical 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>
        Objective: To investigate the efficacy, safety and tolerability of SI-B003 monotherapy and&#xD;
        BL-B01D1+SI-B003 dual agents in patients with locally advanced or metastatic esophageal&#xD;
        cancer, gastric cancer, colorectal cancer and other gastrointestinal tumors, and to further&#xD;
        explore the optimal dose and mode of combination.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Objective: To investigate the efficacy of SI-B003 alone or BL-B01D1+SI-B003 in the treatment&#xD;
        of patients with locally advanced or metastatic esophageal cancer, gastric cancer, colorectal&#xD;
        cancer and other gastrointestinal tumors. To explore the safety and tolerability of SI-B003&#xD;
        alone and BL-B01D1+SI-B003 in patients with locally advanced or metastatic esophageal cancer,&#xD;
        gastric cancer, colorectal cancer and other gastrointestinal tumors, and to further explore&#xD;
        the optimal dose and mode of combination. Secondary objective: To explore the&#xD;
        pharmacokinetics of investigational drugs BL-B01D1 and SI-B003. To explore the immunogenicity&#xD;
        of BL-B01D1 and SI-B003. To explore drug-drug interactions (DDI).&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">September 2025</completion_date>
    <primary_completion_date type="Anticipated">September 2025</primary_completion_date>
    <phase>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>Objective response rate (ORR)</measure>
      <time_frame>Up to approximately 24 months</time_frame>
      <description>ORR is defined as the percentage of participants, who has a CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experiences a confirmed CR or PR is according to RECIST 1.1.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Recommended Phase II Dose (RP2D)</measure>
      <time_frame>Up to approximately 24 months</time_frame>
      <description>The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for phase II study, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation study .</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Progression-free survival (PFS)</measure>
      <time_frame>Up to approximately 24 months</time_frame>
      <description>The PFS is defined as the time from the first dose of medication to disease progression or death, whichever occurred first.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease control rate (DCR)</measure>
      <time_frame>Up to approximately 24 months</time_frame>
      <description>The DCR is defined as the percentage of participants who has a CR, PR, or Stable Disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD]).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of response (DOR)</measure>
      <time_frame>Up to approximately 24 months</time_frame>
      <description>The DOR for a responder is defined as the time from the participant's initial objective response to the first date of either disease progression or death, whichever occurs first.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Treatment-Emergent Adverse Event (TEAE)</measure>
      <time_frame>Up to approximately 24 months</time_frame>
      <description>TEAE is defined as any adverse and unexpected change in body structure, function, or chemistry or any exacerbation of an existing condition (i.e., any clinically significant adverse change in frequency and/or intensity) during treatment. The type, frequency, and severity of TEAE will be assessed during treatment.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">190</enrollment>
    <condition>Esophageal Cancer</condition>
    <condition>Gastric Cancer</condition>
    <condition>Colorectal Cancer</condition>
    <arm_group>
      <arm_group_label>SI-B003 or BL-B01D1 + SI-B003</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants received SI-B003 or BL-B01D1 + SI-B003 therapy in the first cycle (3 weeks). Participants who had a clinical benefit could receive additional cycles of additional treatment. Administration will be discontinued because of disease progression or intolerable toxicity or for other reasons.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>SI-B003</intervention_name>
      <description>SI-B003 was administered intravenously every 3 weeks (Q3W).</description>
      <arm_group_label>SI-B003 or BL-B01D1 + SI-B003</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>BL-B01D1</intervention_name>
      <description>BL-B01D1 was administered by intravenous infusion on D1 and D8 in a 3-week cycle.</description>
      <arm_group_label>SI-B003 or BL-B01D1 + SI-B003</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Voluntarily sign the informed consent and follow the requirements of the protocol;&#xD;
  &#xD;
            2. No gender limit;&#xD;
  &#xD;
            3. Age: ≥18 years old and ≤75 years old;&#xD;
  &#xD;
            4. expected survival time ≥3 months;&#xD;
  &#xD;
            5. Patients with locally advanced or metastatic esophageal cancer, gastric cancer,&#xD;
               colorectal cancer and other gastrointestinal tumors confirmed by histopathology and/or&#xD;
               cytology; Note: Gastric cancer requires definitive HER2 positivity (IHC 3+ or IHC 2+&#xD;
               /ISH +) or HER2 negativity (IHC 2+ /ISH- or IHC 1+). RAS genotype should be determined&#xD;
               in colorectal cancer.&#xD;
  &#xD;
            6. Consent to provide archival tumor tissue samples or fresh tissue samples from primary&#xD;
               or metastatic lesions within 2 years; Participants who were unable to provide tumor&#xD;
               tissue samples could be enrolled if they met other inclusion and exclusion criteria&#xD;
               after evaluation by investigators;&#xD;
  &#xD;
            7. Must have at least one measurable lesion according to RECIST v1.1 definition;&#xD;
  &#xD;
            8. ECOG 0 or 1;&#xD;
  &#xD;
            9. Toxicity of previous antineoplastic therapy has returned to grade 1 or less as defined&#xD;
               by NCI-CTCAE v5.0 (except for asymptomatic laboratory abnormalities considered by&#xD;
               investigators, such as elevated alkaline phosphatase, hyperuricemia, and elevated&#xD;
               blood glucose; Toxicities that were judged by the investigators to be no safety risk,&#xD;
               such as alopecia and grade 2 peripheral neurotoxicity, were excluded. Or decreased&#xD;
               hemoglobin (≥90 g/L);&#xD;
  &#xD;
           10. No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;&#xD;
  &#xD;
           11. Organ function levels must meet the following criteria if blood transfusions, cell&#xD;
               growth factors, and/or platelet-raising agents are not allowed within 14 days prior to&#xD;
               screening:&#xD;
  &#xD;
                 1. Bone marrow function: absolute neutrophil count (ANC) ≥1.5×109/L, platelet count&#xD;
                    ≥90×109/L, hemoglobin ≥90 g/L;&#xD;
  &#xD;
                 2. Liver function: total bilirubin (TBIL≤1.5 ULN), AST and ALT ≤2.5 ULN in patients&#xD;
                    without liver metastasis, AST and ALT ≤5.0 ULN in patients with liver metastasis;&#xD;
  &#xD;
                 3. Renal function: creatinine (Cr) ≤1.5 ULN, or creatinine clearance (Ccr) ≥50&#xD;
                    mL/min (according to Cockcroft and Gault formula).&#xD;
  &#xD;
           12. Coagulation function: international normalized ratio (INR) ≤1.5, and activated partial&#xD;
               thromboplastin time (APTT) ≤1.5 ULN;&#xD;
  &#xD;
           13. Urine protein ≤2+ or ≤1000mg/24h;&#xD;
  &#xD;
           14. For premenopausal women with childbearing potential, a pregnancy test must be&#xD;
               performed within 7 days before the start of treatment, serum or urine must be negative&#xD;
               for pregnancy, and must be non-lactating; All enrolled patients (male or female) were&#xD;
               advised to use adequate barrier contraception throughout the treatment cycle and for 6&#xD;
               months after the end of treatment.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Anti-tumor therapy such as chemotherapy, biological therapy, immunotherapy, radical&#xD;
               radiotherapy, major surgery, and targeted therapy (including small-molecule tyrosine&#xD;
               kinase inhibitors) have been used within 4 weeks or 5 half-life periods (whichever is&#xD;
               shorter) before the first dose in this study; Mitomycin and nitrosoureas were&#xD;
               administered within 6 weeks before the first dose; Oral fluorouracil drugs such as&#xD;
               S-1, capecitabine, or palliative radiotherapy within 2 weeks before the first dose;&#xD;
  &#xD;
            2. The use of immunomodulatory drugs within 2 weeks before the first dose of this study,&#xD;
               including but not limited to thymosin, interleukin-2, interferon, etc., must be&#xD;
               excluded;&#xD;
  &#xD;
            3. Systemic corticosteroid therapy (&gt; 10mg/ day prednisone, or other corticosteroid&#xD;
               equivalent) within 2 weeks before the first dose of the study; Exceptions were inhaled&#xD;
               or topical corticosteroids or physiological replacement doses of corticosteroids for&#xD;
               adrenal insufficiency;&#xD;
  &#xD;
            4. Patients with prior immunotherapy and grade ≥3 irAE or grade ≥2 immune-related&#xD;
               myocarditis defined according to the CSCO guidelines must be excluded;&#xD;
  &#xD;
            5. History of severe heart disease, such as symptomatic congestive heart failure (CHF) ≥&#xD;
               grade 2 (CTCAE 5.0), New York Heart Association (NYHA) ≥ grade 2 heart failure,&#xD;
               transmural myocardial infarction, unstable angina, etc;&#xD;
  &#xD;
            6. Prolonged QT interval (QTc &gt; 450 msec in men or QTc &gt; 470 msec in women), complete&#xD;
               left bundle branch block, and III degree atrioventricular block;&#xD;
  &#xD;
            7. Active autoimmune and inflammatory diseases, such as systemic lupus erythematosus,&#xD;
               psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory bowel&#xD;
               disease, and Hashimoto's thyroiditis; Type I diabetes mellitus, hypothyroidism that&#xD;
               can be controlled only by replacement therapy, and skin diseases (such as vitiligo and&#xD;
               psoriasis) that do not require systemic treatment were excluded;&#xD;
  &#xD;
            8. Other malignant tumors diagnosed within 5 years before the first drug administration&#xD;
               in this study, except for radical skin basal cell carcinoma, skin squamous cell&#xD;
               carcinoma, superficial bladder cancer, radical resection of carcinoma in situ, such as&#xD;
               breast carcinoma in situ;&#xD;
  &#xD;
            9. Prior to the initiation of study treatment, present:&#xD;
  &#xD;
                 1. Poorly controlled diabetes (fasting blood glucose ≥ 13.3 mmol/L)&#xD;
  &#xD;
                 2. Poorly controlled hypertension (systolic blood pressure ≥ 140 mmHg and/or&#xD;
                    diastolic blood pressure ≥ 90 mmHg)&#xD;
  &#xD;
                 3. History of hypertensive crisis or hypertensive encephalopathy.&#xD;
  &#xD;
           10. Pulmonary disease defined as grade ≥3 according to CTCAE v5.0; The patient was&#xD;
               diagnosed with grade ≥1 radiation pneumonitis according to the RTOG/EORTC definition.&#xD;
               Patients with existing or a history of interstitial lung disease (ILD);&#xD;
  &#xD;
           11. Unstable deep vein thrombosis, arterial thrombosis, and pulmonary embolism requiring&#xD;
               medical intervention within 6 months before screening; Infusion-related thrombosis was&#xD;
               excluded;&#xD;
  &#xD;
           12. Unstable (poorly controlled clinical symptoms or requiring drainage) patients with&#xD;
               serous effusion such as pericardial effusion, pleural effusion, and peritoneal&#xD;
               effusion;&#xD;
  &#xD;
           13. Patients with central nervous system (CNS) metastases and/or carcinomatous meningitis&#xD;
               (meningeal metastases). Patients who had received treatment for brain metastases&#xD;
               (radiotherapy or surgery; Patients with stable brain metastases who had stopped&#xD;
               radiotherapy or surgery 28 days before the first dose were eligible. Patients with&#xD;
               cancerous meningitis (meningeal metastasis) were excluded even if they were treated&#xD;
               and judged to be stable. Stability is defined as meeting the following four criteria:&#xD;
  &#xD;
                 1. seizure-free status for &gt; 12 weeks with or without antiepileptic medication;&#xD;
  &#xD;
                 2. no need for corticosteroids;&#xD;
  &#xD;
                 3. stable on two consecutive MRI scans (at least 4 weeks apart);&#xD;
  &#xD;
                 4. stable and asymptomatic for more than one month after treatment.&#xD;
  &#xD;
           14. Patients with a history of allergy to recombinant humanized antibody or human-mouse&#xD;
               chimeric antibody or any of the ingredients of BL-B01D1 or SI-B003;&#xD;
  &#xD;
           15. Prior organ transplantation or allogeneic hematopoietic stem cell transplantation&#xD;
               (Allo-HSCT);&#xD;
  &#xD;
           16. Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active&#xD;
               hepatitis B virus infection (HBV-DNA copy number &gt; 103 IU/ml) or hepatitis C virus&#xD;
               infection (HCV antibody positive and HCV-RNA &gt; detection limit);&#xD;
  &#xD;
           17. Active infection requiring systemic treatment, such as severe pneumonia, bacteremia,&#xD;
               sepsis, etc;&#xD;
  &#xD;
           18. Enrollment in another clinical trial within 4 weeks before the first dose of this&#xD;
               study (calculated from the time of the last dose);&#xD;
  &#xD;
           19. Patients who received live vaccine within 4 weeks before the first dose in the study;&#xD;
  &#xD;
           20. Patients with a history of mental illness or drug abuse who are unable to comply with&#xD;
               clinical trial requirements;&#xD;
  &#xD;
           21. Other conditions for participation in the trial were not considered appropriate 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>Lin Shen</last_name>
      <role>Principal Investigator</role>
      <affiliation>Peking University Cancer Hospital &amp; Institute</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Hai Zhu, PHD</last_name>
      <phone>+8613980051002</phone>
      <email>zhuhai@baili-pharm.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Sa Xiao, PHD</last_name>
      <phone>+8615013238943</phone>
      <email>xiaosa@baili-pharm.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Beijing Cancer Hospital</name>
        <address>
          <city>Beijing</city>
          <state>Beijing</state>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Lin Shen</last_name>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 16, 2023</study_first_submitted>
    <study_first_submitted_qc>August 16, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 23, 2023</study_first_posted>
    <last_update_submitted>August 22, 2023</last_update_submitted>
    <last_update_submitted_qc>August 22, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 24, 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>Colorectal Neoplasms</mesh_term>
      <mesh_term>Stomach Neoplasms</mesh_term>
      <mesh_term>Esophageal Neoplasms</mesh_term>
      <mesh_term>Digestive System Neoplasms</mesh_term>
      <mesh_term>Gastrointestinal Neoplasms</mesh_term>
    </condition_browse>
    <!-- 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/NCT06008054
  org study id: BL-B01D1-SI-B003-201-05
  nct id: NCT06008054
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Objective: To investigate the efficacy, safety and tolerability of SI-B003 monotherapy and
        BL-B01D1+SI-B003 dual agents in patients with locally advanced or metastatic esophageal
        cancer, gastric cancer, colorectal cancer and other gastrointestinal tumors, and to further
        explore the optimal dose and mode of combination.
  Objective: To investigate the efficacy of SI-B003 alone or BL-B01D1+SI-B003 in the treatment
        of patients with locally advanced or metastatic esophageal cancer, gastric cancer, colorectal
        cancer and other gastrointestinal tumors. To explore the safety and tolerability of SI-B003
        alone and BL-B01D1+SI-B003 in patients with locally advanced or metastatic esophageal cancer,
        gastric cancer, colorectal cancer and other gastrointestinal tumors, and to further explore
        the optimal dose and mode of combination. Secondary objective: To explore the
        pharmacokinetics of investigational drugs BL-B01D1 and SI-B003. To explore the immunogenicity
        of BL-B01D1 and SI-B003. To explore drug-drug interactions (DDI).
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Objective response rate (ORR)
  time frame: Up to approximately 24 months
  description: ORR is defined as the percentage of participants, who has a CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experiences a confirmed CR or PR is according to RECIST 1.1.
  measure: Recommended Phase II Dose (RP2D)
  time frame: Up to approximately 24 months
  description: The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for phase II study, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation study .
  measure: Progression-free survival (PFS)
  time frame: Up to approximately 24 months
  description: The PFS is defined as the time from the first dose of medication to disease progression or death, whichever occurred first.
  measure: Disease control rate (DCR)
  time frame: Up to approximately 24 months
  description: The DCR is defined as the percentage of participants who has a CR, PR, or Stable Disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD]).
  measure: Duration of response (DOR)
  time frame: Up to approximately 24 months
  description: The DOR for a responder is defined as the time from the participant's initial objective response to the first date of either disease progression or death, whichever occurs first.
  measure: Treatment-Emergent Adverse Event (TEAE)
  time frame: Up to approximately 24 months
  description: TEAE is defined as any adverse and unexpected change in body structure, function, or chemistry or any exacerbation of an existing condition (i.e., any clinically significant adverse change in frequency and/or intensity) during treatment. The type, frequency, and severity of TEAE will be assessed during treatment.
  arm group label: SI-B003 or BL-B01D1 + SI-B003
  arm group type: Experimental
  description: Participants received SI-B003 or BL-B01D1 + SI-B003 therapy in the first cycle (3 weeks). Participants who had a clinical benefit could receive additional cycles of additional treatment. Administration will be discontinued because of disease progression or intolerable toxicity or for other reasons.
  intervention type: Drug
  intervention name: SI-B003
  description: SI-B003 was administered intravenously every 3 weeks (Q3W).
  arm group label: SI-B003 or BL-B01D1 + SI-B003
  intervention type: Drug
  intervention name: BL-B01D1
  description: BL-B01D1 was administered by intravenous infusion on D1 and D8 in a 3-week cycle.
  arm group label: SI-B003 or BL-B01D1 + SI-B003
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Lin Shen
  role: Principal Investigator
  affiliation: Peking University Cancer Hospital & Institute
  last name: Hai Zhu, PHD
  phone: +8613980051002
  email: zhuhai@baili-pharm.com
  last name: Sa Xiao, PHD
  phone: +8615013238943
  email: xiaosa@baili-pharm.com
  facility: 
  contact: 
  country: China
  responsible party type: Sponsor
  mesh term: Colorectal Neoplasms
  mesh term: Stomach Neoplasms
  mesh term: Esophageal Neoplasms
  mesh term: Digestive System Neoplasms
  mesh term: Gastrointestinal Neoplasms