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/NCT05965856</url>
    </required_header>
    <id_info>
      <org_study_id>BL-B01D1-SI-B003-201-06</org_study_id>
      <nct_id>NCT05965856</nct_id>
    </id_info>
    <brief_title>A Study of BL-B01D1+SI-B003 in the Treatment of Locally Advanced or Metastatic Urothelial Carcinoma and Other Solid Tumors</brief_title>
    <official_title>A Phase II Clinical Study to Evaluate the Efficacy and Safety of BL-B01D1 Combined With SI-B003 in the Treatment of Patients With Locally Advanced or Metastatic Urothelial Carcinoma and Other Solid 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 BL-B01D1+SI-B003&#xD;
        combination in patients with locally advanced or metastatic urothelial carcinoma and other&#xD;
        solid tumors, and to further explore the optimal dose and mode of combination.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        To explore the efficacy of BL-B01D1+SI-B003 combination therapy in patients with locally&#xD;
        advanced or metastatic urothelial carcinoma and other solid tumors. To explore the safety and&#xD;
        tolerability of BL-B01D1+SI-B003 combination in patients with locally advanced or metastatic&#xD;
        urothelial carcinoma and other solid tumors, and to further explore the optimal dose and mode&#xD;
        of combination.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 2023</start_date>
    <completion_date type="Anticipated">August 2025</completion_date>
    <primary_completion_date type="Anticipated">August 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 of SI-B003.</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">40</enrollment>
    <condition>Urothelial Carcinoma</condition>
    <arm_group>
      <arm_group_label>BL-B01D1 + SI-B003</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants received BL-B01D1 combined with SI-B003 dual 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>BL-B01D1</intervention_name>
      <description>Administration by intravenous infusion</description>
      <arm_group_label>BL-B01D1 + SI-B003</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>SI-B003</intervention_name>
      <description>Administration by intravenous infusion</description>
      <arm_group_label>BL-B01D1 + SI-B003</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. All subjects voluntarily participated in the study and signed informed consent;&#xD;
  &#xD;
            2. Male or female aged ≥18 years and ≤75 years;&#xD;
  &#xD;
            3. Expected survival time ≥3 months;&#xD;
  &#xD;
            4. ECOG 0-1;&#xD;
  &#xD;
            5. Locally advanced or metastatic urothelial carcinoma and other solid tumors confirmed&#xD;
               by histopathology and/or cytology who have failed or cannot tolerate standard&#xD;
               treatment or who currently have no standard treatment or cannot obtain standard&#xD;
               treatment; (including but not limited to urothelial cancer, prostate cancer, kidney&#xD;
               cancer) : ① Urothelial cancer should have received previous failure or intolerance to&#xD;
               standard platinum-based chemotherapy; ② Prostate cancer with pathological type of&#xD;
               adenocarcinoma should have received at least one previous novel hormonal therapy&#xD;
               (abiraterone acetate, enzalutamide, etc.) and at least one failed or intolerant taxane&#xD;
               regimen (docetaxel, cabazitaxel); ③ Clear cell renal cell carcinoma required previous&#xD;
               failure or intolerance to standard first-line tyrosine kinase inhibitor (TKI)&#xD;
               regimens. ④ Locally advanced or metastatic other urological malignancies (non-clear&#xD;
               cell renal cancer, penile cancer, etc.) that failed standard treatment and were not&#xD;
               suitable for surgery or radiotherapy. Treatment failure was defined as disease&#xD;
               progression during or after treatment with systemic antitumor regimens. Intolerance&#xD;
               refers to patients who have received standard treatment and have grade 3-4 adverse&#xD;
               reactions, and refuse to continue the original regimen.&#xD;
  &#xD;
               Note: Recurrence or disease progression within 6 months of the last chemotherapy in&#xD;
               multimodal therapy was considered as first-line treatment.&#xD;
  &#xD;
            6. Consent to provide archival tumor tissue specimens (10 unstained sections (anti-slip)&#xD;
               surgical specimens (thickness 4-5μm)) or fresh tissue samples from primary or&#xD;
               metastatic lesions within 3 years. If participants cannot provide tumor tissue&#xD;
               samples, they can be enrolled if they meet other inclusion and exclusion criteria,&#xD;
               after the evaluation of the investigator;&#xD;
  &#xD;
            7. Must have at least one measurable lesion according to RECIST v1.1 definition; Lesions&#xD;
               that had been previously treated with radiation could be included in a measurable&#xD;
               lesion only if there was definite disease progression after radiation therapy.&#xD;
  &#xD;
            8. Provided that no blood transfusions and no use of any cell growth factors and/or&#xD;
               platelet-raising agents are allowed for 14 days prior to the screening period, organ&#xD;
               function levels must meet the following criteria:&#xD;
  &#xD;
                 1. Blood routine: hemoglobin (HGB) ≥ 90g/L; Absolute neutrophil count (NEUT) ≥1.5×10&#xD;
                    9 /L; Platelet count (PLT) ≥ 100×10 9 /L;&#xD;
  &#xD;
                 2. Renal function: creatinine (Cr) ≤1.5 ULN, or creatinine clearance (Ccr) ≥40&#xD;
                    mL/min (according to Cockcroft and Gault formula).&#xD;
  &#xD;
                 3. Liver function: total bilirubin (TBIL≤1.5 ULN), alanine aminotransferase (ALT)&#xD;
                    and aspartate aminotransferase (AST) were all ≤2.5 ULN, and AST and ALT were both&#xD;
                    ≤5.0 ULN when liver metastasis was present;&#xD;
  &#xD;
                 4. Coagulation function: international normalized ratio (INR) ≤1.5 and activated&#xD;
                    partial thromboplastin time (APTT) ≤1.5ULN;&#xD;
  &#xD;
                 5. no severe cardiac dysfunction with left ventricular ejection fraction ≥50%;&#xD;
  &#xD;
            9. Toxicity from previous antineoplastic therapy has returned to grade 1 or less as&#xD;
               defined by NCI-CTCAE v5.0 (asymptomatic laboratory abnormalities such as ALP&#xD;
               elevation, hyperuricemia, and hyperglycemia were considered by the investigator, and&#xD;
               toxicity with no safety risk was judged by the investigator; Except for alopecia,&#xD;
               grade 2 peripheral neurotoxicity, or decreased hemoglobin ≥90g/L).&#xD;
  &#xD;
           10. For premenopausal women with childbearing potential, a pregnancy test must be&#xD;
               performed within 7 days before the start of treatment, the serum or urine pregnancy&#xD;
               test must be negative, and the patient must not be lactating; All enrolled patients&#xD;
               should take adequate barrier contraception during the entire treatment cycle and for 6&#xD;
               months after the end of treatment.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Previous use of an ADC drug with a topoisomerase I inhibitor as a toxin;&#xD;
  &#xD;
            2. Administration of chemotherapy or chemotherapy within 4 weeks or 5 half-lives,&#xD;
               whichever is shorter, before the first dose Physical therapy, immunotherapy,&#xD;
               definitive radiotherapy, major surgery (investigator's definition), targeted therapy&#xD;
               (including Small molecule tyrosine kinase inhibitors) and other anti-tumor therapy;&#xD;
               Mitomycin and nitrosoureas were given for the first time Within 6 weeks before&#xD;
               treatment; Oral fluorouracil drugs such as S-1, capecitabine, or palliative&#xD;
               radiotherapy for Within 2 weeks before the first dose; No exposure to wide-field&#xD;
               radiotherapy within 4 weeks before study treatment for prostate cancer (tired) And&#xD;
               ≥30% bone marrow), samarium must be completed 4 weeks prior to the first dose of&#xD;
               treatment, and strontium and Lu 177 treatment This must be completed at least 12 weeks&#xD;
               before the first administration of treatment, and radium-233 must precede the first&#xD;
               administration of treatment At least 6 weeks to complete. Prostate cancer bone&#xD;
               metastasis therapy such as bisphosphonates or denosumab should be administered before&#xD;
               the first dose It was initiated at 4 weeks and was administered at a stable dose.&#xD;
  &#xD;
            3. Patients with a history of immunotherapy and grade ≥3 irAE or grade ≥2 immune-related&#xD;
               myocarditis must be excluded;&#xD;
  &#xD;
            4. Use of immunomodulatory drugs within 14 days before the first use of the study drug,&#xD;
               including but not limited to thymosin, Interleukin-2, interferon, etc. must be&#xD;
               excluded;&#xD;
  &#xD;
            5. A history of severe cardiovascular and cerebrovascular diseases, including but not&#xD;
               limited to:&#xD;
  &#xD;
                 1. severe cardiac rhythm or conduction abnormalities, such as ventricular&#xD;
                    arrhythmias or grade III atria requiring clinical intervention Ventricular block;&#xD;
  &#xD;
                 2. prolonged QT interval at rest (QTc &gt; 450 msec in men or QTc &gt; 470 msec in women);&#xD;
  &#xD;
                 3. cerebrovascular accident or transient ischemic attack within 6 months before the&#xD;
                    first dose; Symptomatic congestive History of heart failure (CHF) ≥ grade 2&#xD;
                    (CTCAE 5.0) and New York Heart Association (NYHA) ≥ Grade 2 heart failure,&#xD;
                    transmural myocardial infarction history, unstable angina, etc.&#xD;
  &#xD;
            6. Active autoimmune diseases and inflammatory diseases, such as systemic lupus&#xD;
               erythematosus, requiring systemic treatment Psoriasis, rheumatoid arthritis,&#xD;
               inflammatory bowel disease and Hashimoto's thyroiditis, etc., excluding type I sugar&#xD;
               Urinary disorders, hypothyroidism that can be controlled with replacement therapy&#xD;
               alone, skin disorders that do not require systemic treatment (e.g Vitiligo and&#xD;
               psoriasis).&#xD;
  &#xD;
            7. Systemic corticosteroids (&gt; 10mg/ day prednisone, or equivalent) are required within 2&#xD;
               weeks before the study dose Doses of other corticosteroids) or immunosuppressive&#xD;
               agents; Inhaled or topical administration of hormones, or due to adrenal The exception&#xD;
               is those who were treated with physiological replacement doses of hormone for&#xD;
               insufficiency;&#xD;
  &#xD;
            8. Other malignancies that progressed or required treatment within 5 years before the&#xD;
               first dose, such as the following External: radical resection of skin basal cell&#xD;
               carcinoma, skin squamous cell carcinoma, superficial bladder cancer, radical resection&#xD;
               of carcinoma in situ, such as breast carcinoma in situ, prostate cancer; Remarks:&#xD;
               Localized low-risk prostate cancer (Defined as stage ≤T2a, Gleason score ≤6, and PSA &lt;&#xD;
               10ng/mL at prostate cancer diagnosis (e.g Measured) had received curative treatment&#xD;
               and had no PSA biochemical recurrence Were eligible to participate in this study);&#xD;
  &#xD;
            9. History of (noninfectious) interstitial lung disease (ILD)/pulmonary inflammation&#xD;
               requiring steroid therapy, or when Patients with previous ILD/ pulmonary inflammation,&#xD;
               or suspected ILD/ pulmonary inflammation that could not be excluded by imaging at the&#xD;
               time of screening Syndrome;&#xD;
  &#xD;
           10. Prior to starting the study treatment, there are:&#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;
           11. Unstable deep vein thrombosis, arterial thrombosis, and pulmonary embolism requiring&#xD;
               medical intervention within 6 months before screening Thrombotic events such as plug;&#xD;
               Infusion-related thrombosis was excluded.&#xD;
  &#xD;
           12. Patients with central nervous system (CNS) metastases and/or carcinomatous meningitis&#xD;
               (meningeal metastases). But he had a brain turn Metastatic therapy (radiotherapy or&#xD;
               surgery; And the subjects had stopped radiotherapy and surgery 2 weeks before the&#xD;
               first dose.) Patients with stable brain metastases less than 10mm in diameter were&#xD;
               eligible for enrollment Patients (with leptomeningeal metastases) were excluded even&#xD;
               if they were treated and judged to be stable.&#xD;
  &#xD;
           13. Patients with large amount of serous cavity effusion, or serous cavity effusion with&#xD;
               symptoms, or before signing informed consent Patients who underwent drainage within 4&#xD;
               weeks;&#xD;
  &#xD;
           14. Allergic history to recombinant humanized antibody or human-mouse chimeric antibody or&#xD;
               to BL-B01D1, SI-B003 Patients who are allergic to excipients;&#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 active hepatitis C&#xD;
               virus infection (anti-HCV Body 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. Participated in another clinical trial within 4 weeks before the first dose&#xD;
               (calculated from the time of the last dose);&#xD;
  &#xD;
           19. Persons who have a history of psychotropic drug abuse and cannot be abstinent or have&#xD;
               mental disorders;&#xD;
  &#xD;
           20. Any other circumstances that the investigator deemed inappropriate for participation&#xD;
               in the trial.&#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>Dingwei Ye, PHD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Fudan University</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>Fudan University Shanghai Cancer Center</name>
        <address>
          <city>Shanghai</city>
          <state>Shanghai</state>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Dingwei Ye</last_name>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 20, 2023</study_first_submitted>
    <study_first_submitted_qc>July 20, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">July 28, 2023</study_first_posted>
    <last_update_submitted>July 27, 2023</last_update_submitted>
    <last_update_submitted_qc>July 27, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 1, 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>Carcinoma</mesh_term>
      <mesh_term>Carcinoma, Transitional Cell</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/NCT05965856
  org study id: BL-B01D1-SI-B003-201-06
  nct id: NCT05965856
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Objective: To investigate the efficacy, safety and tolerability of BL-B01D1+SI-B003
        combination in patients with locally advanced or metastatic urothelial carcinoma and other
        solid tumors, and to further explore the optimal dose and mode of combination.
  To explore the efficacy of BL-B01D1+SI-B003 combination therapy in patients with locally
        advanced or metastatic urothelial carcinoma and other solid tumors. To explore the safety and
        tolerability of BL-B01D1+SI-B003 combination in patients with locally advanced or metastatic
        urothelial carcinoma and other solid tumors, and to further explore the optimal dose and mode
        of combination.
  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 of SI-B003.
  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: BL-B01D1 + SI-B003
  arm group type: Experimental
  description: Participants received BL-B01D1 combined with SI-B003 dual 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: BL-B01D1
  description: Administration by intravenous infusion
  arm group label: BL-B01D1 + SI-B003
  intervention type: Drug
  intervention name: SI-B003
  description: Administration by intravenous infusion
  arm group label: BL-B01D1 + SI-B003
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Dingwei Ye, PHD
  role: Principal Investigator
  affiliation: Fudan University
  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: Carcinoma
  mesh term: Carcinoma, Transitional Cell