<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/NCT03287427</url>
  </required_header>
  <id_info>
    <org_study_id>MYPHISMO</org_study_id>
    <nct_id>NCT03287427</nct_id>
  </id_info>
  <brief_title>MYPHISMO: MYB and PD-1 Immunotherapies Against Multiple Oncologies Trial</brief_title>
  <acronym>MYPHISMO</acronym>
  <official_title>First-in-human Phase I Clinical Trial of a Combined Immune Modulatory Approach Using TetMYB Vaccine and Anti-PD1 Antibody in Patients With Advanced Solid Cancer Including Colorectal or Adenoid Cystic Carcinoma.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peter MacCallum Cancer Centre, Australia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Peter MacCallum Cancer Centre, Australia</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this research study is to look at the effects, good or bad, of TetMYB Vaccine&#xD;
      in combination with BGB-A317 in patients with advanced or metastatic solid cancers (including&#xD;
      colorectal or adenoid cystic cancer).&#xD;
&#xD;
      The immune system is the body's defence against cancer, bacteria and viruses. TetMYB Vaccine&#xD;
      is a vaccine that helps your immune system to recognise the cancer cells. BGB-A317 is an&#xD;
      antibody (a type of protein made in the body in response to a foreign substance) that helps&#xD;
      to stop or reverse the growth of tumour cells.&#xD;
&#xD;
      Up to 32 participants may take part in this study, which is divided into 2 stages: dose&#xD;
      escalation (different doses will be tested in small groups of patients) and dose expansion&#xD;
      (one or more doses may be tested in a larger group of patients). Which stage you participate&#xD;
      in will depend on which is open at the time. Your study doctor will discuss this with you.&#xD;
&#xD;
      During dose escalation, study patients will receive increasing doses of the TetMYB Vaccine,&#xD;
      starting at a low dose. During dose expansion, study patients will receive the dose&#xD;
      determined as safe in dose escalation.&#xD;
&#xD;
      The study design is as follows:&#xD;
&#xD;
      In the dose finding stage, the first patient of each dose level will receive 6 consecutive&#xD;
      weekly doses of intradermal TetMYB monotherapy for safety evaluation. If there are no&#xD;
      reported DLTs, the next 2 patients of the same dose level will also receive 6 consecutive&#xD;
      weekly intradermal doses of TetMYB, however with 3 weekly doses of BGB-A317 commencing with&#xD;
      the fourth TetMYB dose. The dosage of TetMYB are as follows:&#xD;
&#xD;
        -  Dose level 1: 100 ug in 100 uL of sterile dH2O containing 5% DMSO&#xD;
&#xD;
        -  Dose level 2: 500 ug in 100 uL of sterile dH2O containing 5% DMSO&#xD;
&#xD;
        -  Dose level 3: 1000 ug in 100 uL of sterile dH2O containing 5% DMSO.&#xD;
&#xD;
      In the dose expansion stage, the dosage will be the maximum tolerated dose (MTD) identified&#xD;
      in the dose-finding stage and in combination with BGB-A317.&#xD;
&#xD;
      TetMYB Vaccine is being developed and manufactured by the Peter MacCallum Cancer Centre&#xD;
      according to Good Manufacturing Practice (GMP) and in accordance with guidelines provided by&#xD;
      the Food and Drug Administration (FDA) in the USA and Therapeutic Goods Administration (TGA)&#xD;
      in Australia. TetMYB Vaccine is an experimental treatment and is currently not approved for&#xD;
      use in any country. This means that it is not an approved treatment for cancer in Australia.&#xD;
      This will be the first time that the TetMYB vaccine is given to humans.&#xD;
&#xD;
      BGB-A317 is being developed by BeiGene, a biopharmaceutical company. BGB-A317 is an&#xD;
      experimental treatment. This means that it is not an approved treatment for solid cancers in&#xD;
      Australia.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 22, 2018</start_date>
  <completion_date type="Actual">December 14, 2022</completion_date>
  <primary_completion_date type="Actual">December 14, 2022</primary_completion_date>
  <phase>Phase 1</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>The incidence of Grade 3 or 4 or greater adverse events (AEs) according to CTCAE v4.03 criteria and clinical laboratory abnormalities defined as dose-limiting toxicities (DLTs).</measure>
    <time_frame>End of Week 6</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Tolerability of the treatment as defined as receiving a minimum of 4 doses of TetMYB Vaccine within 6 weeks of starting treatment.</measure>
    <time_frame>End of Week 6</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The occurrence, type, severity and relationship to treatment of adverse events occurring after the first 6 weeks of treatment, described according to CTCAE v4.03 criteria.</measure>
    <time_frame>Week 7 and through study completion, an average of 12 months.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The objective response as defined by the achievement of a complete (irCR) or partial (irPR) response, based on irRECIST criteria within 12 weeks of first vaccination.</measure>
    <time_frame>End of Week 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical benefit as defined by wither the achievement of a complete (irCR) or partial (irPR) response as per irRECIST criteria; or the maintenance of stable disease (irSD), as per irRECIST criteria, at 12 weeks after commencement of treatment.</measure>
    <time_frame>End of Week 12.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS) as defined as the time from first vaccination to the earliest of date of disease progression as assessed by irRECIST or death from any cause.</measure>
    <time_frame>From the date of treatment commencement to until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS) as defined as the time from first vaccination to date of death from any cause.</measure>
    <time_frame>From the date of treatment commencement to the date of death from any cause, whichever came first, assessed up to 48 months..</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To demonstrate a MYB-specific immune response through epitope stimulation of PBMCs and assessment with CBA, FACS for IFN-γ and TNF-α production, and via the evaluation of changes in tumour microenvironment in pre- and post-treatment biopsies.</measure>
    <time_frame>Through study completion, an average of 48 months.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To assess metabolic response, as assessed by FDG-PET scan.</measure>
    <time_frame>Week 4, at the time of disease progression and 4 weeks after treatment is ceased.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The objective immune response as defined by achievement of a complete or partial response (irCR or irPR), based on irRECIST criteria.</measure>
    <time_frame>End of week 12.</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">27</enrollment>
  <condition>Colorectal Cancer</condition>
  <condition>Adenoid Cystic Carcinoma</condition>
  <arm_group>
    <arm_group_label>TetMYB Vaccine &amp; BGB-A317</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TetMYB Vaccine</intervention_name>
    <description>Weekly intra-dermal injections of either 0.1mg, 0.5mg or 1.0mg on day 1 for week 1 to week 6.</description>
    <arm_group_label>TetMYB Vaccine &amp; BGB-A317</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BGB-A317</intervention_name>
    <description>3 weekly IV injections of 200mg commencing from Week 4.</description>
    <arm_group_label>TetMYB Vaccine &amp; BGB-A317</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female aged 18 years or older at screening.&#xD;
&#xD;
          2. Patients with advanced/metastatic colorectal or adenoid cystic carcinoma; for which no&#xD;
             effective standard therapy is available.&#xD;
&#xD;
          3. Patient has been fully informed about the study and is willing to participate in the&#xD;
             study, and has provided written informed consent prior to any trial specific screening&#xD;
             procedures.&#xD;
&#xD;
          4. Measurable disease as per irRECIST criteria 1.1.&#xD;
&#xD;
          5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.&#xD;
&#xD;
          6. Life expectancy greater than 3 months.&#xD;
&#xD;
          7. Adequate haematological, renal and hepatic functions as defined by:&#xD;
&#xD;
               -  Neutrophil count &gt;1.5 x 109/L&#xD;
&#xD;
               -  Platelets &gt;100 x 109/L&#xD;
&#xD;
               -  Hb &gt;100 g/L (Patients can be transfused in the lead-in period, providing they do&#xD;
                  not have active bleeding or require regular transfusions)&#xD;
&#xD;
               -  Total bilirubin &lt;1.5x upper limit of normal (ULN)&#xD;
&#xD;
               -  ALT and AST &lt;2.5x ULN (&lt;5.0x ULN for patients with hepatic metastasis)&#xD;
&#xD;
               -  Serum creatinine &lt;1.5x ULN or Creatinine Clearance &gt;50 mL/min (Cockcroft-Gault or&#xD;
                  Nuclear GFR method)&#xD;
&#xD;
          8. Willing to provide study specific pre-treatment biopsy of tumour and allow use of&#xD;
             archival tumour biopsies. This is optional for adenoid cystic carcinoma patients.&#xD;
&#xD;
          9. Willing to consent to the use of their collected fresh tumour and archival FFPE&#xD;
             specimen and blood samples as detailed in the protocol for research including but not&#xD;
             limited to DNA, RNA and protein based biomarker detection.&#xD;
&#xD;
         10. Men and women of childbearing potential must use adequate contraception to prevent&#xD;
             pregnancy during the study. Adequate contraception is defined in the study as any&#xD;
             medically recommended method (or combination of methods) as per standard of care. An&#xD;
             adequate contraception includes hormonal contraception with implants or combined oral,&#xD;
             transdermal or injectable contraceptives, certain intrauterine devices, bilateral&#xD;
             tubal ligation, hysterectomy, or vasectomy of partner. Combinations of male condom&#xD;
             with either cap, diaphragm or sponge with spermicide are also considered acceptable.&#xD;
             For women of childbearing age, a negative pregnancy test needs to be confirmed before&#xD;
             inclusion.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior therapy with an anti-cancer vaccine; or anti-PD-1, anti-PD-L1, anti-PD-L2,&#xD;
             anti-CD137, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting&#xD;
             T-cell co-stimulation or immune checkpoint pathways.&#xD;
&#xD;
          2. Chemotherapy, radioactive, biological cancer therapy, or tyrosine kinase inhibitor&#xD;
             (TKI) therapy, within four weeks prior to the first dose of study drug. All toxicities&#xD;
             attributed to prior anti-cancer therapy other than alopecia and fatigue must have&#xD;
             resolved to Grade 1 (NCI CTCAE v4.03) or baseline before administration of study drug.&#xD;
&#xD;
          3. Patient has had a prior malignancy active within the previous 3 years except for&#xD;
             locally curable cancers that have been apparently cured, such as basal or squamous&#xD;
             cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or&#xD;
             breast, or localized prostate cancer.&#xD;
&#xD;
          4. Uncontrolled or significant intercurrent or recent illness including:&#xD;
&#xD;
               -  Autoimmune disorder or history of autoimmune disease requiring immunosuppressive&#xD;
                  treatment&#xD;
&#xD;
               -  Cardiac disorder such as uncontrolled cardiac failure, unstable angina or non-ST&#xD;
                  segment elevation myocardial infarction (NSTEMI) or myocardial infarction,&#xD;
                  uncontrolled arrhythmia less than 3 months before screening&#xD;
&#xD;
               -  Active or uncontrolled severe infection&#xD;
&#xD;
          5. History of solid organ transplantation or any condition requiring chronic treatment&#xD;
             with corticosteroids or other immunosuppressive agents.&#xD;
&#xD;
          6. Active coagulopathy/bleeding diathesis.&#xD;
&#xD;
          7. Cirrhosis, chronic active or untreated persistent hepatitis.&#xD;
&#xD;
          8. Active Hepatitis B: (defined as having a positive Hepatitis B surface antigen [HBsAg]&#xD;
             test at screening). Patients with past or resolved Hepatitis B infection (defined as&#xD;
             having a negative HBsAg test and a positive IgG antibody to Hepatitis B core antigen&#xD;
             [anti-HBc]) are eligible. Hepatitis B virus (HBV) DNA must be obtained in these&#xD;
             patients prior to Cycle 1, Day 1, and must demonstrate no active infection.&#xD;
&#xD;
          9. Active Hepatitis C: Patients positive for Hepatitis C virus (HCV) antibody are&#xD;
             eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.&#xD;
&#xD;
         10. History of adverse reactions to peptide vaccines.&#xD;
&#xD;
         11. Patients who are pregnant or lactating.&#xD;
&#xD;
         12. Has received an investigational drug within 4 weeks prior to first dose of study drug,&#xD;
             or unless other has been agreed with the SSC.&#xD;
&#xD;
         13. Is currently receiving any agent with a known effect on the immune system, unless at&#xD;
             dose levels that is not immunosuppressive (e.g. prednisone at 10 mg/day or less or as&#xD;
             inhaled steroid at doses used for the treatment of asthma).&#xD;
&#xD;
         14. Known history of positive tests for HIV/AIDS.&#xD;
&#xD;
         15. Prior treated brain metastases must be without evidence of progression (through&#xD;
             magnetic resonance imaging [MRI] with contrast - preferred method or contrast enhanced&#xD;
             computed tomography [CT]) for at least 4 weeks and off immunosuppressive doses of&#xD;
             systemic medications, such as steroids (doses &gt; 10 mg/day prednisone or equivalent)&#xD;
             for at least 2 weeks before study drug administration to be eligible&#xD;
&#xD;
         16. Receipt of live, attenuated vaccine within 28 days prior to the first dose of study&#xD;
             drug (Note: Subjects, if enrolled, should not receive live vaccine during the study&#xD;
             and 180 days after the last dose of study drug).&#xD;
&#xD;
         17. Any contraindication to receiving anti-PD-1 antibody (BGB-A317) or hypersensitivity to&#xD;
             the constituents of BGB-A317.&#xD;
&#xD;
         18. Has a history or current evidence of any condition, therapy, or laboratory abnormality&#xD;
             that might confound the results of the trial, interfere with the patient's&#xD;
             participation for the full duration of the trial, or is not in the best interest of&#xD;
             the patient to participate, in the opinion of the treating investigator.&#xD;
&#xD;
         19. Has known psychiatric or substance abuse disorders that would interfere with&#xD;
             cooperation with the requirements of the trial.&#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>Jayesh Desai</last_name>
    <role>Principal Investigator</role>
    <affiliation>Peter MacCallum Cancer Centre, Australia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Peter MacCallum Cancer Centre</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>September 12, 2017</study_first_submitted>
  <study_first_submitted_qc>September 15, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 19, 2017</study_first_posted>
  <last_update_submitted>February 13, 2023</last_update_submitted>
  <last_update_submitted_qc>February 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Advanced</keyword>
  <keyword>Metastatic</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Adenoid Cystic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tislelizumab</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/NCT03287427
org study id: MYPHISMO
nct id: NCT03287427
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
The purpose of this research study is to look at the effects, good or bad, of TetMYB Vaccine
      in combination with BGB-A317 in patients with advanced or metastatic solid cancers (including
      colorectal or adenoid cystic cancer).

      The immune system is the body's defence against cancer, bacteria and viruses. TetMYB Vaccine
      is a vaccine that helps your immune system to recognise the cancer cells. BGB-A317 is an
      antibody (a type of protein made in the body in response to a foreign substance) that helps
      to stop or reverse the growth of tumour cells.

      Up to 32 participants may take part in this study, which is divided into 2 stages: dose
      escalation (different doses will be tested in small groups of patients) and dose expansion
      (one or more doses may be tested in a larger group of patients). Which stage you participate
      in will depend on which is open at the time. Your study doctor will discuss this with you.

      During dose escalation, study patients will receive increasing doses of the TetMYB Vaccine,
      starting at a low dose. During dose expansion, study patients will receive the dose
      determined as safe in dose escalation.

      The study design is as follows:

      In the dose finding stage, the first patient of each dose level will receive 6 consecutive
      weekly doses of intradermal TetMYB monotherapy for safety evaluation. If there are no
      reported DLTs, the next 2 patients of the same dose level will also receive 6 consecutive
      weekly intradermal doses of TetMYB, however with 3 weekly doses of BGB-A317 commencing with
      the fourth TetMYB dose. The dosage of TetMYB are as follows:

        -  Dose level 1: 100 ug in 100 uL of sterile dH2O containing 5% DMSO

        -  Dose level 2: 500 ug in 100 uL of sterile dH2O containing 5% DMSO

        -  Dose level 3: 1000 ug in 100 uL of sterile dH2O containing 5% DMSO.

      In the dose expansion stage, the dosage will be the maximum tolerated dose (MTD) identified
      in the dose-finding stage and in combination with BGB-A317.

      TetMYB Vaccine is being developed and manufactured by the Peter MacCallum Cancer Centre
      according to Good Manufacturing Practice (GMP) and in accordance with guidelines provided by
      the Food and Drug Administration (FDA) in the USA and Therapeutic Goods Administration (TGA)
      in Australia. TetMYB Vaccine is an experimental treatment and is currently not approved for
      use in any country. This means that it is not an approved treatment for cancer in Australia.
      This will be the first time that the TetMYB vaccine is given to humans.

      BGB-A317 is being developed by BeiGene, a biopharmaceutical company. BGB-A317 is an
      experimental treatment. This means that it is not an approved treatment for solid cancers in
      Australia.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The incidence of Grade 3 or 4 or greater adverse events (AEs) according to CTCAE v4.03 criteria and clinical laboratory abnormalities defined as dose-limiting toxicities (DLTs).
time frame: End of Week 6
measure: Tolerability of the treatment as defined as receiving a minimum of 4 doses of TetMYB Vaccine within 6 weeks of starting treatment.
time frame: End of Week 6
measure: The occurrence, type, severity and relationship to treatment of adverse events occurring after the first 6 weeks of treatment, described according to CTCAE v4.03 criteria.
time frame: Week 7 and through study completion, an average of 12 months.
measure: The objective response as defined by the achievement of a complete (irCR) or partial (irPR) response, based on irRECIST criteria within 12 weeks of first vaccination.
time frame: End of Week 12
measure: Clinical benefit as defined by wither the achievement of a complete (irCR) or partial (irPR) response as per irRECIST criteria; or the maintenance of stable disease (irSD), as per irRECIST criteria, at 12 weeks after commencement of treatment.
time frame: End of Week 12.
measure: Progression free survival (PFS) as defined as the time from first vaccination to the earliest of date of disease progression as assessed by irRECIST or death from any cause.
time frame: From the date of treatment commencement to until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months.
measure: Overall survival (OS) as defined as the time from first vaccination to date of death from any cause.
time frame: From the date of treatment commencement to the date of death from any cause, whichever came first, assessed up to 48 months..
measure: To demonstrate a MYB-specific immune response through epitope stimulation of PBMCs and assessment with CBA, FACS for IFN-γ and TNF-α production, and via the evaluation of changes in tumour microenvironment in pre- and post-treatment biopsies.
time frame: Through study completion, an average of 48 months.
measure: To assess metabolic response, as assessed by FDG-PET scan.
time frame: Week 4, at the time of disease progression and 4 weeks after treatment is ceased.
measure: The objective immune response as defined by achievement of a complete or partial response (irCR or irPR), based on irRECIST criteria.
time frame: End of week 12.
arm group label: TetMYB Vaccine & BGB-A317
arm group type: Experimental
intervention type: Drug
intervention name: TetMYB Vaccine
description: Weekly intra-dermal injections of either 0.1mg, 0.5mg or 1.0mg on day 1 for week 1 to week 6.
arm group label: TetMYB Vaccine & BGB-A317
intervention type: Drug
intervention name: BGB-A317
description: 3 weekly IV injections of 200mg commencing from Week 4.
arm group label: TetMYB Vaccine & BGB-A317
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jayesh Desai
role: Principal Investigator
affiliation: Peter MacCallum Cancer Centre, Australia
facility: 
country: Australia
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Adenoid Cystic
mesh term: Tislelizumab