<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/NCT04478279</url>
  </required_header>
  <id_info>
    <org_study_id>ST101-101</org_study_id>
    <nct_id>NCT04478279</nct_id>
  </id_info>
  <brief_title>A Phase 1-2 Study of ST101 in Patients With Advanced Solid Tumors</brief_title>
  <official_title>A Phase 1-2 Dose-escalation and Expansion Study of ST101 in Patients With Advanced Unresectable and Metastatic Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sapience Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sapience Therapeutics</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open-label, two-part, phase 1-2 dose-finding study designed to determine the&#xD;
      safety, tolerability, PK, PD, and proof-of-concept efficacy of ST101 administered IV in&#xD;
      patients with advanced solid tumors. The study consists of two phases: a phase 1 dose&#xD;
      escalation/regimen exploration phase and a phase 2 expansion phase.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Dose escalation / regimen exploration phase During the dose escalation/regimen exploration&#xD;
      phase, only patients diagnosed with locally advanced or metastatic melanoma, carcinoma or&#xD;
      sarcoma of any tumor type who are refractory or intolerant to all available therapies that&#xD;
      would impact survival will be enrolled.&#xD;
&#xD;
      ST101 will be administered intravenously (IV), initially once per week. The dose escalation&#xD;
      cohorts will be recruited using a standard 3+3 design. At each new dosing cohort, there will&#xD;
      be a 1-week observation period after dosing the first patient in order to assess safety prior&#xD;
      to dosing the remainder of the patients in that cohort. The dose cohorts will be 0.5, 1, 2,&#xD;
      4, 8 and 16 mg/kg with once weekly (QW) dosing in all cohorts except for the highest dose&#xD;
      level which will be dosed every other week (Q2W).&#xD;
&#xD;
      The expansion phase consists of 4 specific tumor-type cohorts, which each follow the same&#xD;
      Simon 2-stage design. Fifteen (15) patients will be enrolled in each cohort and treated with&#xD;
      the ST101 RP2D. If one or more responses is observed that cohort will be expanded to a total&#xD;
      of 30 patients to further assess efficacy.&#xD;
&#xD;
      Responses will be graded using response evaluation criteria in solid tumors (RECIST) 1.1&#xD;
      (Eisenhauer 2009) for hormonal receptor positive (HRpos) locally advanced/metastatic breast&#xD;
      cancer (LA/MBC) and melanoma, modified response assessment in neuro-oncology (RANO)&#xD;
      (Ellingson 2017) for GBM and prostate cancer clinical trials working group 3 (PCWG3) (Scher&#xD;
      2016) for castration-resistant prostate cancer (CRPC).During the expansion phase, only&#xD;
      patients diagnosed with the following tumor types will be allowed into this phase of the&#xD;
      study:&#xD;
&#xD;
        -  HRpos LA/MBC that has progressed after prior 1-2 hormone-based therapies. Previous&#xD;
           treatment with cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, mammalian target of&#xD;
           rapamycin (mTOR) inhibitor or chemotherapy is allowed as monotherapy or in combination.&#xD;
&#xD;
        -  Melanoma that has progressed after/or on treatment with an immune checkpoint inhibitor&#xD;
           (CPI) and have received 1-2 prior lines of therapy for their advanced/metastatic&#xD;
           disease. Patients that have BRAF mutated disease should also have received one line of&#xD;
           appropriate targeted therapy.&#xD;
&#xD;
        -  Primary (de novo) GBM that has recurred or progressed (per modified RANO criteria) after&#xD;
           1 standard treatment regimen. Standard therapy is defined as maximal surgical resection,&#xD;
           radiotherapy, and concomitant temozolomide with radiotherapy or adjuvant chemotherapy&#xD;
           with temozolomide. Patients that undergo tumor treating fields as an adjuvant to first&#xD;
           line therapy are allowed.&#xD;
&#xD;
        -  CRPC that has progressed after previous treatment with taxanes, abiraterone and&#xD;
           enzalutamide/apalutamide.&#xD;
&#xD;
      The tumor types in the expansion phase may change based on emerging data from the dose&#xD;
      escalation phase of this study. Additional mini cohorts of 10 patients may be added to the&#xD;
      expansion phase based on efficacy signals during the dose escalation phase.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 1, 2020</start_date>
  <completion_date type="Anticipated">January 2024</completion_date>
  <primary_completion_date type="Anticipated">October 2023</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>Sequential Assignment</intervention_model>
    <intervention_model_description>The study consists of two phases: a phase 1 dose escalation/regimen exploration phase and a phase 2 expansion phase.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Dose-Limiting Toxicity (DLT)</measure>
    <time_frame>20 months</time_frame>
    <description>Number of Participants with a Dose-Limiting Toxicity (DLT)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Adverse Events</measure>
    <time_frame>20 months</time_frame>
    <description>Number of Participants with at Least One Adverse Event, Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area Under the Curve (AUC)</measure>
    <time_frame>30 Months</time_frame>
    <description>Area under the plasma concentration time curve of ST101</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax</measure>
    <time_frame>20 months</time_frame>
    <description>Peak plasma concentration of ST101</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal Half-Life (t1/2)</measure>
    <time_frame>20 months</time_frame>
    <description>Elimination half-life of ST101</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Response</measure>
    <time_frame>20 months</time_frame>
    <description>Escalation and Expansion Evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DCR</measure>
    <time_frame>20 Months</time_frame>
    <description>Expansion: Disease Control Rate, Assessed According to RECIST v1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response</measure>
    <time_frame>20 months</time_frame>
    <description>Expansion: Duration of Response, Assessed According to RECIST v1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS</measure>
    <time_frame>20 months</time_frame>
    <description>Expansion: Progression Free Survival, Assessed According to RECIST v1.1</description>
  </secondary_outcome>
  <number_of_arms>7</number_of_arms>
  <enrollment type="Anticipated">162</enrollment>
  <condition>Glioblastoma</condition>
  <condition>Melanoma Stage IV</condition>
  <condition>Breast Cancer</condition>
  <condition>Prostate Cancer</condition>
  <condition>Glioblastoma Multiforme</condition>
  <condition>GBM</condition>
  <condition>Brain Cancer</condition>
  <condition>Metastatic Breast Cancer</condition>
  <condition>Metastatic Melanoma</condition>
  <condition>Metastatic Prostate Cancer</condition>
  <condition>Melanoma Recurrent</condition>
  <condition>Prostate Cancer Metastatic</condition>
  <condition>Recurrent Glioblastoma</condition>
  <condition>Newly Diagnosed Glioblastoma</condition>
  <arm_group>
    <arm_group_label>Dose Escalation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This cohort only patients diagnosed with locally advanced or metastatic melanoma, carcinoma or sarcoma of any tumor type who are refractory or intolerant to all available therapies. ST101 will be administered intravenously (IV), initially once per week.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Expansion HR+ Breast</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This cohort must have progressed after 1-2 hormone based therapies. The starting dose of ST101 for Expansion will be derived from the maximum tolerated dose (MTD)/recommended dose for expansion (RDE) and the best dosing schedule determined during Dose Escalation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Expansion Melanoma</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This cohort must have Melanoma that has progressed after/or on treatment with an immune checkpoint inhibitor (CPI) and have received 1-2 prior lines of therapy for their advanced/metastatic disease. The starting dose of ST101 for Expansion will be derived from the maximum tolerated dose (MTD)/recommended dose for expansion (RDE) and the best dosing schedule determined during Dose Escalation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Expansion GBM</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Primary (de novo) GBM that has recurred or progressed (per modified RANO criteria) after 1 standard treatment regimen. Standard therapy is defined as maximal surgical resection, radiotherapy, and concomitant temozolomide with radiotherapy or adjuvant chemotherapy with temozolomide. The starting dose of ST101 for Expansion will be derived from the maximum tolerated dose (MTD)/recommended dose for expansion (RDE) and the best dosing schedule determined during Dose Escalation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Expansion CRPC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>CRPC that has progressed after previous treatment with taxanes, abiraterone and enzalutamide/apalutamide. The starting dose of ST101 for Expansion will be derived from the maximum tolerated dose (MTD)/recommended dose for expansion (RDE) and the best dosing schedule determined during Dose Escalation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Expansion Recurrent Glioblastoma</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Recurrent GBM patients must have completed radiation at least 3 months prior to minimize the inclusion of patients with pseudoprogression. Recurrent GBM patients must have unequivocal radiographic evidence of tumor progression by contrast-enhanced magnetic resonance imaging (MRI) scan within 21 days prior to registration. Patients must be able to delay surgery for 2 - 4 weeks per investigator decision</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Newly Diagnosed Glioblastoma</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Newly diagnosed patients with a suboptimal resection or biopsy must be candidates for another surgical resection as determined by neurosurgical evaluation or multidisciplinary team based on the current standard of care that suggests that maximal safe resection is beneficial. Recurrent GBM patients must be candidates for tumor resection</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ST101</intervention_name>
    <description>ST101 will be administered intravenously (IV), initially once per week with a flat dose on the schedule described for each study arm</description>
    <arm_group_label>Dose Escalation</arm_group_label>
    <arm_group_label>Dose Expansion CRPC</arm_group_label>
    <arm_group_label>Dose Expansion GBM</arm_group_label>
    <arm_group_label>Dose Expansion HR+ Breast</arm_group_label>
    <arm_group_label>Dose Expansion Melanoma</arm_group_label>
    <arm_group_label>Dose Expansion Recurrent Glioblastoma</arm_group_label>
    <arm_group_label>Newly Diagnosed Glioblastoma</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Temozolomide</intervention_name>
    <description>Temozolomide</description>
    <arm_group_label>Newly Diagnosed Glioblastoma</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Radiation</intervention_name>
    <description>Radiation</description>
    <arm_group_label>Newly Diagnosed Glioblastoma</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Inclusion Criteria&#xD;
&#xD;
               1. Able and willing to sign informed consent form (ICF) and comply with the protocol&#xD;
                  and the restrictions and assessments therein.&#xD;
&#xD;
               2. Male or female ≥18 years of age.&#xD;
&#xD;
               3. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.&#xD;
&#xD;
               4. Must have a locally advanced or metastatic inoperable tumor as follows:&#xD;
&#xD;
                    1. For the dose escalation/regimen exploration phase: melanoma, carcinoma, or&#xD;
                       sarcoma&#xD;
&#xD;
                    2. For the expansion phase: HR positive LA/MBC, melanoma, GBM, CRPC&#xD;
&#xD;
               5. Agrees to provide a newly obtained biopsy of an accessible lesion (if they can be&#xD;
                  biopsied based on the investigator's assessment) prior to the start of study&#xD;
                  treatment, and to repeat biopsy once during study treatment. Tissue obtained for&#xD;
                  the biopsy must not be previously irradiated (unless progressing following&#xD;
                  irradiation), but a new or progressing lesion in the radiation field is&#xD;
                  acceptable. Archived biopsies are acceptable for GBM patients.&#xD;
&#xD;
               6. In the investigator's opinion, the patient may not derive clinical benefit from,&#xD;
                  or is ineligible for, a particular form of standard therapy on medical grounds,&#xD;
                  or the patient failed or did not tolerate one or more of other anti-cancer&#xD;
                  therapies:&#xD;
&#xD;
                  a. For the dose escalation/regimen exploration phase up to 3 previous lines of&#xD;
                  systemic anticancer therapies are allowed. Since this is a FIH study, it's&#xD;
                  important that patients are not refractory to therapeutic intervention due to&#xD;
                  multiple lines of prior therapies.&#xD;
&#xD;
                  a. For the expansion phase: i. HRpos LA/MBC must have progressed after prior 1-2&#xD;
                  hormone-based therapies. Previous treatment with cyclin-dependent kinase 4/6&#xD;
                  (CDK4/6) inhibitor, mammalian target of rapamycin (mTOR) inhibitor or&#xD;
                  chemotherapy is allowed as monotherapy or in combination ii. Melanoma that has&#xD;
                  progressed after or on treatment with a CPI and have received 1-2 prior lines of&#xD;
                  therapy for their advanced/metastatic disease. Patients that have BRAF mutated&#xD;
                  disease should also have received one line of appropriate targeted therapy iii.&#xD;
                  Primary (de novo) GBM that has recurred or progressed (per modified RANO&#xD;
                  criteria) after 1 standard treatment regimen (surgery, radiotherapy, and&#xD;
                  temozolomide therapy). Patients that undergo tumor treating fields as an adjuvant&#xD;
                  to first line therapy are allowed.&#xD;
&#xD;
                  iv. CRPC that has progressed after previous treatment with taxanes, abiraterone&#xD;
                  and enzalutamide/apalutamide or that are intolerant to these treatments.&#xD;
&#xD;
               7. Evaluable disease per RECIST 1.1, modified RANO or PCWG3 with at least one target&#xD;
                  lesion&#xD;
&#xD;
               8. Disease that progressed on, or is non-responsive to, the previous line of therapy&#xD;
                  per RECIST 1.1, modified RANO or PCWG3.&#xD;
&#xD;
               9. If not menopausal or surgically sterile, willing to practice at least one of the&#xD;
                  following highly effective methods of birth control for at least a (partner's)&#xD;
                  menstrual cycle before and for four months after ST101 administration: (1) total&#xD;
                  abstinence from sexual intercourse with a member of the opposite sex; (2) sexual&#xD;
                  intercourse with vasectomized male/sterilized female partner; (3) combined&#xD;
                  (estrogen and progestogen containing) or progestogen-only hormonal contraception&#xD;
                  associated with inhibition of ovulation (oral, parenteral, transvaginal or&#xD;
                  transdermal) for at least 3 consecutive months prior to investigational product&#xD;
                  administration; (4) other acceptable forms of birth control (condoms,&#xD;
                  contraceptive sponge, diaphragm or vaginal ring with spermicide or cream); (5)&#xD;
                  use of an intrauterine contraceptive device.&#xD;
&#xD;
              10. All previous anti-cancer therapy-related adverse events should have resolved to&#xD;
                  grade 1 or baseline value with the exception of alopecia. Levothyroxine is&#xD;
                  allowed for patients that previously received a CPI and experienced thyroid&#xD;
                  dysfunction.&#xD;
&#xD;
                  Exclusion Criteria&#xD;
&#xD;
               1. Use of small molecule or tyrosine kinase inhibitor within 2 weeks or 5 half-lives&#xD;
                  (whichever is shorter) prior to the first dose of study drug; chemotherapy,&#xD;
                  investigational drug or biological cancer therapy within 3 weeks prior to the&#xD;
                  first dose of study therapy; nitrosourea or radioisotope within 6 weeks prior to&#xD;
                  first dose.&#xD;
&#xD;
               2. Known hypersensitivity to ST101 or any of its excipients.&#xD;
&#xD;
               3. Baseline corrected interval between q and t wave on electrocardiogram (ECG) (QTc)&#xD;
                  &gt; 480 msec using Fredericia's formula.&#xD;
&#xD;
               4. Symptomatic ascites or pleural effusion. A patient who is clinically stable&#xD;
                  following treatment for these conditions (including therapeutic thoraco- or&#xD;
                  paracentesis) is eligible.&#xD;
&#xD;
               5. Known active central nervous system (CNS) metastases and/or carcinomatous&#xD;
                  meningitis. Patients with previously treated brain metastases may participate&#xD;
                  provided they are clinically stable for at least 4 weeks prior to study entry,&#xD;
                  have no evidence of new or enlarging brain metastases, and are off steroids for&#xD;
                  at least 14 days prior to first dose of study drug. This criterion does not apply&#xD;
                  to patients on the GBM cohort.&#xD;
&#xD;
               6. Presence of any other active malignancy requiring systemic therapy other than the&#xD;
                  disease under study.&#xD;
&#xD;
               7. Active infection with human immunodeficiency virus (HIV) and CD4+ T-cell count&#xD;
                  &lt;350/μL. Patients not on established ART for at least four weeks and having a&#xD;
                  detectable HIV viral load. Testing is not required for eligibility.&#xD;
&#xD;
               8. Active infection with hepatitis B or hepatitis C, defined by a detectable viral&#xD;
                  load. Testing is not required for eligibility.&#xD;
&#xD;
               9. Active autoimmune disease or a documented history of autoimmune disease or&#xD;
                  syndrome that requires systemic steroids or immunosuppressive agents. Vitiligo or&#xD;
                  resolved childhood asthma/atopy are exceptions to this rule. Patients requiring&#xD;
                  intermittent use of bronchodilators or topical steroids would not be excluded&#xD;
                  from the study. Patients with hypothyroidism that is stable on hormone&#xD;
                  replacement or controlled type 1 diabetes will not be excluded from the study.&#xD;
&#xD;
              10. Use of systemic corticosteroids to treat inflammatory or autoimmune symptoms&#xD;
                  within 15 days or other immunosuppressive drugs within 30 days prior to the start&#xD;
                  of the study. Inhaled and topical corticosteroids are permitted. Up to 10 mg/day&#xD;
                  prednisone or equivalent is permitted as replacement therapy for adrenal&#xD;
                  insufficiency only.&#xD;
&#xD;
              11. Active infection requiring systemic therapy.&#xD;
&#xD;
              12. Active immune thrombocytopenic purpura or other chronic thrombocytopenic&#xD;
                  condition.&#xD;
&#xD;
              13. Therapeutic anticoagulation that cannot be interrupted for a biopsy or had a&#xD;
                  thromboembolic event within the last 6 months.&#xD;
&#xD;
              14. History or clinical evidence of any surgical or medical condition which the&#xD;
                  investigator judges as likely to interfere with the results of the study or pose&#xD;
                  an additional risk in participating, or makes the patient unlikely to comply with&#xD;
                  the study related visits and assessments particularly any pre-existing condition&#xD;
                  that would put the patient at additional risk should they experience an&#xD;
                  infusion-related reaction, e.g., rapidly progressive or uncontrolled disease&#xD;
                  involving a major organ system - vascular, cardiac, pulmonary, gastrointestinal,&#xD;
                  gynecologic, hematologic, neurologic, neoplastic, renal, endocrine, or an&#xD;
                  immunodeficiency&#xD;
&#xD;
              15. Unable to comply with the visits and requirements of the protocol due to&#xD;
                  psychiatric condition or substance abuse. Pregnant or breastfeeding or planning&#xD;
                  to conceive or father children within the projected duration of the study.&#xD;
&#xD;
              16. Exclusion Criteria for GBM Cohort:&#xD;
&#xD;
                  a) Any prior therapy for GBM other than that which is considered SOC for primary&#xD;
                  GBM, including but not limited to the following: i. more than one line of&#xD;
                  adjuvant temozolomide ii. prior treatment with another investigational drug iii.&#xD;
                  prior treatment with bevacizumab (Avastin) or other vascular-endothelial growth&#xD;
                  factor (VEGF) inhibitors or VEGF-receptor signaling inhibitors iv. prior&#xD;
                  treatment with nitrosoureas v. prior therapy that included interstitial&#xD;
                  brachytherapy or Gliadel® Wafers (carmustine implants) b) secondary GBM (i.e.,&#xD;
                  GBM that progressed from low-grade diffuse astrocytoma or AA) c) tumor with a&#xD;
                  clinically significant mass effect (&gt;5 mm midline shift) while on a stable&#xD;
                  corticosteroid dose d) prednisone or equivalent dose of &gt;10mg per day e) known&#xD;
                  history of allergy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Abi Vainstein-Haras, MD</last_name>
    <role>Study Chair</role>
    <affiliation>CMO</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Steve Kaesshaefer</last_name>
    <phone>+1 973-715-2917</phone>
    <email>steve.kaesshaefer@bexonclinical.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Rob Michel</last_name>
    <phone>832-713-7198</phone>
    <email>rob.michel@bexonclinical.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of California, San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Stephanie Lewis</last_name>
    </contact>
    <contact_backup>
      <email>stephanie.lewis2@ucsf.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Nicholas Butowski, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80218</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sarah Cannon Nurse Navigators</last_name>
      <phone>615-329-6888</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>Northwestern Medicine Cancer Centers</name>
      <address>
        <city>Warrenville</city>
        <state>Illinois</state>
        <zip>60555</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Neuro Oncology Research Coordinator</last_name>
      <phone>630-938-2085</phone>
      <email>anastasia.papaioannou@nm.org</email>
    </contact>
    <investigator>
      <last_name>Vinai Gondi, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>START Midwest</name>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <zip>49503</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Katie L Robinson, BSN</last_name>
      <phone>616-954-5554</phone>
      <email>katie.robinson@startmidwest.com</email>
    </contact>
    <investigator>
      <last_name>Nehal Lakhani, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Columbia University</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alyssa Schumpp</last_name>
      <phone>212-342-0139</phone>
      <email>as6498@cumc.columbia.edu</email>
    </contact>
    <investigator>
      <last_name>Fabio Iwamoto, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Duke University School of Medicine</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27708</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Katy Peters, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sarah Cannon Nurse Navigators</last_name>
      <phone>615-329-6888</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>Texas Oncology - Baylor Charles A. Sammons Cancer Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Edinburgh Cancer Centre</name>
      <address>
        <city>Edinburgh</city>
        <zip>EH4 2SP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jim MacPherson</last_name>
      <phone>(+44) 013.537.2202</phone>
      <email>Jim.MacPherson@ed.ac.uk</email>
    </contact>
    <investigator>
      <last_name>Stefan Symeonides, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The Beaston West of Scotland Cancer Centre</name>
      <address>
        <city>Glasgow</city>
        <zip>G12 0YN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Thomas Evans, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Leeds</name>
      <address>
        <city>Leeds</city>
        <zip>LS9 7TF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>leedsth-tr.earlyphaseoncology@nhs.net</last_name>
      <email>leedsth-tr.earlyphaseoncology@nhs.net</email>
    </contact>
    <investigator>
      <last_name>Alan Anthoney, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute UK</name>
      <address>
        <city>London</city>
        <zip>W1G 6AD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Anja Williams, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://aacrjournals.org/mct/article/21/11/1632/710057/Anticancer-Activity-of-ST101-A-Novel-Antagonist-of</url>
    <description>Anticancer Activity of ST101, A Novel Antagonist of CCAAT/Enhancer Binding Protein β</description>
  </link>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>July 2, 2020</study_first_submitted>
  <study_first_submitted_qc>July 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 20, 2020</study_first_posted>
  <last_update_submitted>May 26, 2023</last_update_submitted>
  <last_update_submitted_qc>May 26, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 30, 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>Breast Neoplasms</mesh_term>
    <mesh_term>Prostatic Neoplasms</mesh_term>
    <mesh_term>Melanoma</mesh_term>
    <mesh_term>Glioblastoma</mesh_term>
    <mesh_term>Brain Neoplasms</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Temozolomide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04478279
org study id: ST101-101
nct id: NCT04478279
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is an open-label, two-part, phase 1-2 dose-finding study designed to determine the
      safety, tolerability, PK, PD, and proof-of-concept efficacy of ST101 administered IV in
      patients with advanced solid tumors. The study consists of two phases: a phase 1 dose
      escalation/regimen exploration phase and a phase 2 expansion phase.
Dose escalation / regimen exploration phase During the dose escalation/regimen exploration
      phase, only patients diagnosed with locally advanced or metastatic melanoma, carcinoma or
      sarcoma of any tumor type who are refractory or intolerant to all available therapies that
      would impact survival will be enrolled.

      ST101 will be administered intravenously (IV), initially once per week. The dose escalation
      cohorts will be recruited using a standard 3+3 design. At each new dosing cohort, there will
      be a 1-week observation period after dosing the first patient in order to assess safety prior
      to dosing the remainder of the patients in that cohort. The dose cohorts will be 0.5, 1, 2,
      4, 8 and 16 mg/kg with once weekly (QW) dosing in all cohorts except for the highest dose
      level which will be dosed every other week (Q2W).

      The expansion phase consists of 4 specific tumor-type cohorts, which each follow the same
      Simon 2-stage design. Fifteen (15) patients will be enrolled in each cohort and treated with
      the ST101 RP2D. If one or more responses is observed that cohort will be expanded to a total
      of 30 patients to further assess efficacy.

      Responses will be graded using response evaluation criteria in solid tumors (RECIST) 1.1
      (Eisenhauer 2009) for hormonal receptor positive (HRpos) locally advanced/metastatic breast
      cancer (LA/MBC) and melanoma, modified response assessment in neuro-oncology (RANO)
      (Ellingson 2017) for GBM and prostate cancer clinical trials working group 3 (PCWG3) (Scher
      2016) for castration-resistant prostate cancer (CRPC).During the expansion phase, only
      patients diagnosed with the following tumor types will be allowed into this phase of the
      study:

        -  HRpos LA/MBC that has progressed after prior 1-2 hormone-based therapies. Previous
           treatment with cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, mammalian target of
           rapamycin (mTOR) inhibitor or chemotherapy is allowed as monotherapy or in combination.

        -  Melanoma that has progressed after/or on treatment with an immune checkpoint inhibitor
           (CPI) and have received 1-2 prior lines of therapy for their advanced/metastatic
           disease. Patients that have BRAF mutated disease should also have received one line of
           appropriate targeted therapy.

        -  Primary (de novo) GBM that has recurred or progressed (per modified RANO criteria) after
           1 standard treatment regimen. Standard therapy is defined as maximal surgical resection,
           radiotherapy, and concomitant temozolomide with radiotherapy or adjuvant chemotherapy
           with temozolomide. Patients that undergo tumor treating fields as an adjuvant to first
           line therapy are allowed.

        -  CRPC that has progressed after previous treatment with taxanes, abiraterone and
           enzalutamide/apalutamide.

      The tumor types in the expansion phase may change based on emerging data from the dose
      escalation phase of this study. Additional mini cohorts of 10 patients may be added to the
      expansion phase based on efficacy signals during the dose escalation phase.
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: The study consists of two phases: a phase 1 dose escalation/regimen exploration phase and a phase 2 expansion phase.
primary purpose: Treatment
masking: None (Open Label)
measure: Dose-Limiting Toxicity (DLT)
time frame: 20 months
description: Number of Participants with a Dose-Limiting Toxicity (DLT)
measure: Adverse Events
time frame: 20 months
description: Number of Participants with at Least One Adverse Event, Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
measure: Area Under the Curve (AUC)
time frame: 30 Months
description: Area under the plasma concentration time curve of ST101
measure: Cmax
time frame: 20 months
description: Peak plasma concentration of ST101
measure: Terminal Half-Life (t1/2)
time frame: 20 months
description: Elimination half-life of ST101
measure: Overall Response
time frame: 20 months
description: Escalation and Expansion Evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
measure: DCR
time frame: 20 Months
description: Expansion: Disease Control Rate, Assessed According to RECIST v1.1
measure: Duration of Response
time frame: 20 months
description: Expansion: Duration of Response, Assessed According to RECIST v1.1
measure: PFS
time frame: 20 months
description: Expansion: Progression Free Survival, Assessed According to RECIST v1.1
arm group label: Dose Escalation
arm group type: Experimental
description: This cohort only patients diagnosed with locally advanced or metastatic melanoma, carcinoma or sarcoma of any tumor type who are refractory or intolerant to all available therapies. ST101 will be administered intravenously (IV), initially once per week.
arm group label: Dose Expansion HR+ Breast
arm group type: Experimental
description: This cohort must have progressed after 1-2 hormone based therapies. The starting dose of ST101 for Expansion will be derived from the maximum tolerated dose (MTD)/recommended dose for expansion (RDE) and the best dosing schedule determined during Dose Escalation.
arm group label: Dose Expansion Melanoma
arm group type: Experimental
description: This cohort must have Melanoma that has progressed after/or on treatment with an immune checkpoint inhibitor (CPI) and have received 1-2 prior lines of therapy for their advanced/metastatic disease. The starting dose of ST101 for Expansion will be derived from the maximum tolerated dose (MTD)/recommended dose for expansion (RDE) and the best dosing schedule determined during Dose Escalation.
arm group label: Dose Expansion GBM
arm group type: Experimental
description: Primary (de novo) GBM that has recurred or progressed (per modified RANO criteria) after 1 standard treatment regimen. Standard therapy is defined as maximal surgical resection, radiotherapy, and concomitant temozolomide with radiotherapy or adjuvant chemotherapy with temozolomide. The starting dose of ST101 for Expansion will be derived from the maximum tolerated dose (MTD)/recommended dose for expansion (RDE) and the best dosing schedule determined during Dose Escalation.
arm group label: Dose Expansion CRPC
arm group type: Experimental
description: CRPC that has progressed after previous treatment with taxanes, abiraterone and enzalutamide/apalutamide. The starting dose of ST101 for Expansion will be derived from the maximum tolerated dose (MTD)/recommended dose for expansion (RDE) and the best dosing schedule determined during Dose Escalation.
arm group label: Dose Expansion Recurrent Glioblastoma
arm group type: Experimental
description: Recurrent GBM patients must have completed radiation at least 3 months prior to minimize the inclusion of patients with pseudoprogression. Recurrent GBM patients must have unequivocal radiographic evidence of tumor progression by contrast-enhanced magnetic resonance imaging (MRI) scan within 21 days prior to registration. Patients must be able to delay surgery for 2 - 4 weeks per investigator decision
arm group label: Newly Diagnosed Glioblastoma
arm group type: Experimental
description: Newly diagnosed patients with a suboptimal resection or biopsy must be candidates for another surgical resection as determined by neurosurgical evaluation or multidisciplinary team based on the current standard of care that suggests that maximal safe resection is beneficial. Recurrent GBM patients must be candidates for tumor resection
intervention type: Drug
intervention name: ST101
description: ST101 will be administered intravenously (IV), initially once per week with a flat dose on the schedule described for each study arm
arm group label: Dose Escalation
arm group label: Dose Expansion CRPC
arm group label: Dose Expansion GBM
arm group label: Dose Expansion HR+ Breast
arm group label: Dose Expansion Melanoma
arm group label: Dose Expansion Recurrent Glioblastoma
arm group label: Newly Diagnosed Glioblastoma
intervention type: Drug
intervention name: Temozolomide
description: Temozolomide
arm group label: Newly Diagnosed Glioblastoma
intervention type: Radiation
intervention name: Radiation
description: Radiation
arm group label: Newly Diagnosed Glioblastoma
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Abi Vainstein-Haras, MD
role: Study Chair
affiliation: CMO
last name: Steve Kaesshaefer
phone: +1 973-715-2917
email: steve.kaesshaefer@bexonclinical.com
last name: Rob Michel
phone: 832-713-7198
email: rob.michel@bexonclinical.com
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
contact: 
facility: 
status: Withdrawn
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
investigator: 
country: United Kingdom
country: United States
url: https://aacrjournals.org/mct/article/21/11/1632/710057/Anticancer-Activity-of-ST101-A-Novel-Antagonist-of
description: Anticancer Activity of ST101, A Novel Antagonist of CCAAT/Enhancer Binding Protein β
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Prostatic Neoplasms
mesh term: Melanoma
mesh term: Glioblastoma
mesh term: Brain Neoplasms
mesh term: Recurrence
mesh term: Temozolomide
sharing ipd: No