<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/NCT04479241</url>
  </required_header>
  <id_info>
    <org_study_id>LUMINOS-101</org_study_id>
    <nct_id>NCT04479241</nct_id>
  </id_info>
  <brief_title>LUMINOS-101: Lerapolturev (PVSRIPO) and Pembrolizumab in Patients With Recurrent Glioblastoma</brief_title>
  <official_title>A Phase 2, Open-label, Single-arm Study Evaluating the Efficacy, Safety and Tolerability of Lerapolturev (PVSRIPO) and the Immune Checkpoint Inhibitor Pembrolizumab in the Treatment of Patients With Recurrent Glioblastoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Istari Oncology, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Istari Oncology, Inc.</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 Phase 2 single arm trial in patients with rGBM will characterize the efficacy, safety,&#xD;
      tolerability and initial efficacy of lerapolturev intratumoral infusion followed by&#xD;
      intravenous pembrolizumab 14 to 28 days later, and every 3 weeks, thereafter.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 21, 2020</start_date>
  <completion_date type="Anticipated">March 2023</completion_date>
  <primary_completion_date type="Anticipated">March 2023</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), Duration of response (DOR) and Durable Radiographic Response (DRR)</measure>
    <time_frame>24 months</time_frame>
    <description>Objective response rate (comprised of patients meeting an objective radiographic response or ORR): Patients achieving a CR or PR.&#xD;
DOR: Time from first ORR observed (once confirmed) until PD first observed (once confirmed) or death; whichever comes first.&#xD;
DRR: An ORR that persists for ≥ 6 months.&#xD;
All response must be confirmed via two consecutive MRI assessments at least 4 weeks apart. If on bevacizumab therapy when response first noted, response will be confirmed ≥ 8 weeks off bevacizumab, via MRI.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Frequency and severity of treatment-emergent adverse events</measure>
    <time_frame>24 months</time_frame>
    <description>Assess safety and tolerability of lerapolturev followed by pembrolizumab via frequency and severity of treatment-emergent adverse events (TEAE) via Common Terminology Criteria for Adverse Events (CTCAE, v5.0)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease control rate (DCR)</measure>
    <time_frame>24 months</time_frame>
    <description>Proportion of patients achieving stable disease (SD), CR or PR via protocol-specified response criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of disease control (DDC)</measure>
    <time_frame>24 months</time_frame>
    <description>DDC ≥ 6 months for those meeting DCR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival time</measure>
    <time_frame>24 months</time_frame>
    <description>If calculable, progression free survival (PFS) will be estimated based on the time from lerapolturev infusion to death or confirmed progression</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival assessed by Kaplan-Meier methods</measure>
    <time_frame>24 months</time_frame>
    <description>Overall and landmark survival assessed by the proportion of patients alive at ≥ 6, ≥ 12 and at 24 months post-lerapolturev infusion estimated by Kaplan-Meier methods.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Biomarker identification</measure>
    <time_frame>24 months</time_frame>
    <description>Assessment of tumor tissue and blood samples for identification of genetic, cytologic, histologic and/or other markers that correlate with anti-tumor response.</description>
  </other_outcome>
  <other_outcome>
    <measure>Radiographic response/progression/PFS via iRANO</measure>
    <time_frame>24 months</time_frame>
    <description>Alternative assessment of radiographic response/progression/PFS via iRANO</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Glioblastoma</condition>
  <condition>Recurrent Glioblastoma</condition>
  <condition>Supratentorial Glioblastoma</condition>
  <condition>Brain Tumor</condition>
  <arm_group>
    <arm_group_label>Lerapolturev</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>lerapolturev</intervention_name>
    <description>Lerapolturev (5x10^7 TCID50) delivered intratumorally via convection enhanced delivery (CED).</description>
    <arm_group_label>Lerapolturev</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>pembrolizumab</intervention_name>
    <description>Pembrolizumab (200 mg IV) given every 3 weeks.</description>
    <arm_group_label>Lerapolturev</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. ≥ 18 years of age.&#xD;
&#xD;
          2. Recurrent supratentorial glioblastoma confirmed via prior histology by the site's&#xD;
             neuropathologist or designate.&#xD;
&#xD;
               -  Histologically confirmed recurrent glioblastoma within 6 weeks of Lerapolturev&#xD;
                  infusion will not require a biopsy to confirm active tumor prior to catheter&#xD;
                  placement&#xD;
&#xD;
               -  Progression of primary glioblastoma or transformation from a lower grade to a&#xD;
                  higher grade is acceptable for recurrence and as for primary glioblastoma, must&#xD;
                  be confirmed via prior histology by site pathologist&#xD;
&#xD;
          3. Enhancing lesion ≥1 cm shortest diameter to ≤ 5.5 cm longest diameter in all planes.&#xD;
&#xD;
          4. Before catheter placement based on screening MRI and at the time of catheter placement&#xD;
             via CT prior to infusion, neurosurgical investigator must confirm placement of&#xD;
             infusion catheter within or through the progressive enhancing tumor is feasible and at&#xD;
             a safe distance relative to eloquent brain function, with the tip of the catheter&#xD;
             being placed:&#xD;
&#xD;
               1. Within the enhancing portion or in the vicinity of enhancement of target lesion&#xD;
                  (ie, infiltrative disease).&#xD;
&#xD;
               2. ≥ 0.5 cm from ventricles.&#xD;
&#xD;
               3. ≥ 1 cm deep into the brain.&#xD;
&#xD;
               4. ≥ 0.5 cm from corpus callosum.&#xD;
&#xD;
          5. First or second relapse supported by MRI or CT scan; relapse is defined as progression&#xD;
             following initial/prior therapy(ies).&#xD;
&#xD;
          6. Failed previous first line therapy: maximum surgical resection and radiotherapy (RT)&#xD;
             (plus concomitant chemotherapy followed by maintenance chemotherapy if unknown or&#xD;
             methylated O6-methylguanine-DNA methyltransferase (MGMT) promoter). Patients who begin&#xD;
             but do not complete chemotherapy/RT may still be considered for eligibility at the&#xD;
             discretion of Sponsor.&#xD;
&#xD;
          7. Karnofsky Performance Status ≥ 70 at screening and baseline.&#xD;
&#xD;
          8. Undergone prior vaccination against PV and received a boost immunization with&#xD;
             trivalent inactivated poliovirus vaccine (IPOL®) at least 1 week, but less than 6&#xD;
             weeks, prior to administration of Lerapolturev. Note: Patients who are unsure of their&#xD;
             prior vaccination status/who have not been vaccinated must provide proof of&#xD;
             vaccination and/or evidence of anti-PV immunity prior to enrollment, as applicable.&#xD;
&#xD;
          9. Ability to safely discontinue anti-coagulant therapy(ies) prior to biopsy/catheter&#xD;
             placement, as required per site/surgical guidelines.&#xD;
&#xD;
         10. Hemoglobin ≥ 9 g/dL prior to biopsy/catheter placement.&#xD;
&#xD;
         11. Platelet count ≥ 100,000/μL (unsupported); ≥ 125,000/ μL (can be supported via&#xD;
             platelet transfusion) at biopsy/catheter placement.&#xD;
&#xD;
         12. ANC ≥ 1000/μL prior to biopsy/catheter placement.&#xD;
&#xD;
         13. Creatinine ≤ 1.2 x ULN prior to biopsy/catheter placement.&#xD;
&#xD;
         14. Total bilirubin, ALT, AST, ALP ≤ 2.5 x ULN prior to biopsy/catheter placement.&#xD;
&#xD;
         15. PT and aPTT ≤ 1.2 x ULN prior to biopsy/catheter placement.&#xD;
&#xD;
         16. If undetectable ATT IgG at screen, Tdap booster vaccine ≥ 1 week prior to&#xD;
             biopsy/catheter placement.&#xD;
&#xD;
         17. Patients must be willing and able to understand and provide written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-&#xD;
             CTLA-4 antibody (including ipilimumab or any other antibody or drug specifically&#xD;
             targeting T-cell co-stimulation or checkpoint pathways) ≤ 12 weeks prior to&#xD;
             lerapolturev infusion (Note: does not apply for patients treated with pembrolizumab&#xD;
             under this protocol who are eligible for lerapolturev retreatment). Note: patients who&#xD;
             had previously permanently discontinued any anti-PD-1 or PD-L1 therapy due to severe&#xD;
             or life-threatening immune-related AE are excluded.&#xD;
&#xD;
          2. Excluded are:&#xD;
&#xD;
               1. Neoplastic lesions in the brainstem, cerebellum, or spinal cord.&#xD;
&#xD;
               2. Radiological evidence of active/growing multifocal disease: no size increase &gt;&#xD;
                  0.5 cm in any direction of any other enhancing non-target lesions present at&#xD;
                  baseline confirmed via most recent, prior, consecutive MRIs at least 3 months&#xD;
                  apart.&#xD;
&#xD;
               3. Tumors with ≥ 1cm of contrast-enhancing tumor component crossing the midline&#xD;
                  (crossing the corpus callosum).&#xD;
&#xD;
               4. Extensive subependymal disease: multiple lesions or lesions covering &gt; 50% of&#xD;
                  subependymal space. Tumor touching subependymal space allowed.&#xD;
&#xD;
               5. Extensive leptomeningeal disease: multiple lesions or lesions covering &gt; 50% of&#xD;
                  leptomeninges. Tumor touching leptomeninges allowed.&#xD;
&#xD;
          3. Has received systemic immunosuppressive treatments other than systemic corticosteroids&#xD;
             (eg, methotrexate, chloroquine, azathioprine) within six months of Lerapolturev&#xD;
             infusion.&#xD;
&#xD;
          4. Requires treatment with high dose systemic corticosteroids, defined as dexamethasone &gt;&#xD;
             4 mg/day or equivalent, within 2 weeks of Lerapolturev infusion.&#xD;
&#xD;
          5. Prior interstitial brachytherapy, implanted chemotherapy, stereotactic radiosurgery or&#xD;
             therapeutics delivered by local injection or CED, including Lerapolturev (except for&#xD;
             qualifying patients being retreated with Lerapolturev within this trial).&#xD;
&#xD;
          6. Pregnant and/or breast feeding female; patient/female partner of childbearing&#xD;
             potential who is unwilling to utilize protocol-defined acceptable form of&#xD;
             contraception for duration of study.&#xD;
&#xD;
          7. Impending/life-threatening cerebral herniation syndrome, per neurosurgeon/designate.&#xD;
&#xD;
          8. Severe, active co-morbidity, defined as follows:&#xD;
&#xD;
               1. Infection requiring IV treatment/unexplained febrile illness (Tmax &gt;&#xD;
                  99.5°F/37.5°C)&#xD;
&#xD;
               2. Known immunosuppressive disease/human immunodeficiency virus infection&#xD;
&#xD;
               3. Known active hepatitis B or C infection via positive viral DNA or RNA,&#xD;
                  respectively&#xD;
&#xD;
               4. Unstable or severe intercurrent medical conditions such as severe heart disease&#xD;
                  (New York Heart Association Class 3 or 4)&#xD;
&#xD;
               5. Known lung disease with forced expiratory volume in 1st second of expiration &lt;&#xD;
                  50%&#xD;
&#xD;
               6. Uncontrolled diabetes mellitus (eg, hemoglobin A1C level &gt; 7.0% with treatment)&#xD;
&#xD;
               7. History of other malignancy requiring active treatment within 2 years of&#xD;
                  biopsy/catheter placement with the exception of those with a negligible risk of&#xD;
                  metastasis or death (eg, resected cutaneous basal cell carcinoma, or other&#xD;
                  cancers with 5-year OS of &gt;90%)&#xD;
&#xD;
          9. Known albumin allergy.&#xD;
&#xD;
         10. Uncontrolled unexplained bleeding and/or hemoptysis within 4 weeks of planned&#xD;
             lerapolturev infusion.&#xD;
&#xD;
         11. Inability to undergo brain MRI with and without contrast. History of&#xD;
             severe/anaphylactic reaction to gadolinium contrast agent is excluded. Mild allergy&#xD;
             (eg, rash) acceptable with prophylactic acetaminophen and diphenhydramine.&#xD;
&#xD;
         12. History of neurological complications due to PV infection.&#xD;
&#xD;
         13. Not recovered from toxic side effects (alopecia acceptable) and/or no current or prior&#xD;
             tumor treatments within the following timeframe relative to biopsy/catheter placement:&#xD;
&#xD;
               1. Chemotherapy or bevacizumab ≤ 4 weeks (except for nitrosourea (6 weeks) or&#xD;
                  metronomic dosed chemotherapy/targeted therapies such as daily temozolomide,&#xD;
                  etoposide or cyclophosphamide (1 week)).&#xD;
&#xD;
               2. Tumor treating fields ≤ 7 days.&#xD;
&#xD;
               3. RT of brain ≤ 12 weeks, except for progressive disease outside of the radiation&#xD;
                  field or 2 progressive scans at least 4 weeks apart or histopathologic&#xD;
                  confirmation.&#xD;
&#xD;
         14. History of agammaglobulinemia.&#xD;
&#xD;
         15. Known hypersensitivity to pembrolizumab, or any components of pembrolizumab.&#xD;
&#xD;
         16. Active autoimmune disease requiring systemic immunomodulatory treatment within the&#xD;
             past 12 months; physiologic replacement therapy (eg, thyroxine, insulin, or&#xD;
             physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency)&#xD;
             is not considered a form of systemic treatment.&#xD;
&#xD;
         17. History of other malignancy requiring active treatment within 2 years of&#xD;
             biopsy/catheter placement with the exception of those with a negligible risk of&#xD;
             metastasis or death (eg, resected cutaneous basal cell carcinoma, or other cancers&#xD;
             with 5-year OS of &gt;90%)&#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>Lisa Franklin</last_name>
    <role>Study Director</role>
    <affiliation>Istari Oncology</affiliation>
  </overall_official>
  <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>
  </location>
  <location>
    <facility>
      <name>UConn Health</name>
      <address>
        <city>Farmington</city>
        <state>Connecticut</state>
        <zip>06030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baptist MD Anderson Cancer Center</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beth Israel Deaconess Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals Cleveland Medical Center</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ohio State University</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Health and Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>July 16, 2020</study_first_submitted>
  <study_first_submitted_qc>July 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 21, 2020</study_first_posted>
  <last_update_submitted>December 9, 2022</last_update_submitted>
  <last_update_submitted_qc>December 9, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 13, 2022</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>Glioblastoma</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04479241
org study id: LUMINOS-101
nct id: NCT04479241
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This Phase 2 single arm trial in patients with rGBM will characterize the efficacy, safety,
      tolerability and initial efficacy of lerapolturev intratumoral infusion followed by
      intravenous pembrolizumab 14 to 28 days later, and every 3 weeks, thereafter.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Response Rate (ORR), Duration of response (DOR) and Durable Radiographic Response (DRR)
time frame: 24 months
description: Objective response rate (comprised of patients meeting an objective radiographic response or ORR): Patients achieving a CR or PR.
DOR: Time from first ORR observed (once confirmed) until PD first observed (once confirmed) or death; whichever comes first.
DRR: An ORR that persists for ≥ 6 months.
All response must be confirmed via two consecutive MRI assessments at least 4 weeks apart. If on bevacizumab therapy when response first noted, response will be confirmed ≥ 8 weeks off bevacizumab, via MRI.
measure: Frequency and severity of treatment-emergent adverse events
time frame: 24 months
description: Assess safety and tolerability of lerapolturev followed by pembrolizumab via frequency and severity of treatment-emergent adverse events (TEAE) via Common Terminology Criteria for Adverse Events (CTCAE, v5.0)
measure: Disease control rate (DCR)
time frame: 24 months
description: Proportion of patients achieving stable disease (SD), CR or PR via protocol-specified response criteria
measure: Duration of disease control (DDC)
time frame: 24 months
description: DDC ≥ 6 months for those meeting DCR
measure: Progression free survival time
time frame: 24 months
description: If calculable, progression free survival (PFS) will be estimated based on the time from lerapolturev infusion to death or confirmed progression
measure: Survival assessed by Kaplan-Meier methods
time frame: 24 months
description: Overall and landmark survival assessed by the proportion of patients alive at ≥ 6, ≥ 12 and at 24 months post-lerapolturev infusion estimated by Kaplan-Meier methods.
measure: Biomarker identification
time frame: 24 months
description: Assessment of tumor tissue and blood samples for identification of genetic, cytologic, histologic and/or other markers that correlate with anti-tumor response.
measure: Radiographic response/progression/PFS via iRANO
time frame: 24 months
description: Alternative assessment of radiographic response/progression/PFS via iRANO
arm group label: Lerapolturev
arm group type: Experimental
intervention type: Biological
intervention name: lerapolturev
description: Lerapolturev (5x10^7 TCID50) delivered intratumorally via convection enhanced delivery (CED).
arm group label: Lerapolturev
intervention type: Biological
intervention name: pembrolizumab
description: Pembrolizumab (200 mg IV) given every 3 weeks.
arm group label: Lerapolturev
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Lisa Franklin
role: Study Director
affiliation: Istari Oncology
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Glioblastoma
mesh term: Recurrence
mesh term: Pembrolizumab