<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/NCT03815682</url>
  </required_header>
  <id_info>
    <org_study_id>TT-101</org_study_id>
    <secondary_id>KEYNOTE KN-948</secondary_id>
    <nct_id>NCT03815682</nct_id>
  </id_info>
  <brief_title>RPTR-147 in Patients With Selected Solid Tumors and Lymphomas</brief_title>
  <official_title>A Phase 1/2 Study of Deep IL-15 Loaded T-Cells Alone and in Combination With Pembrolizumab in Patients With Select Solid Tumors and Lymphomas</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Repertoire Immune Medicines</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Repertoire Immune Medicines</source>
  <oversight_info>
    <has_dmc>No</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>
      The purpose of this study is to assess the safety and tolerability of escalating doses of&#xD;
      RPTR-147 as a monotherapy and in combination with Pembrolizumab in patients with selected&#xD;
      solid tumors and lymphomas.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a first-in-human, open-label, multicenter, dose escalation study designed to&#xD;
      determine the safety and tolerability of RPTR-147 as a monotherapy and in combination with&#xD;
      Pembrolizumab in patients with selected solid tumors or lymphomas.&#xD;
&#xD;
      The study will include 2 dosing periods: A Dose Escalation (Phase 1) followed by an Expansion&#xD;
      (Phase 2).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Development program terminated&#xD;
  </why_stopped>
  <start_date type="Actual">October 24, 2018</start_date>
  <completion_date type="Actual">October 11, 2022</completion_date>
  <primary_completion_date type="Actual">September 7, 2022</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of subjects with dose limiting toxicities</measure>
    <time_frame>At the end of cycle 1 (Each cycle is 28 days)</time_frame>
    <description>Safety of RPTR-147:1 as a monotherapy</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with dose limiting toxicities</measure>
    <time_frame>At the end of cycle 1 (Each cycle is 21 days)</time_frame>
    <description>Safety of RPTR-147:1 in combination with pembrolizumab</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with dose limiting toxicities</measure>
    <time_frame>At the end of cycle 1 (Each cycle is 21 days)</time_frame>
    <description>Safety of RPTR-147:2 as a monotherapy</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Frequency of dose interruptions</measure>
    <time_frame>At the end of cycle 1 (Each cycle is 28 days)</time_frame>
    <description>Tolerability of RPTR-147:1 as a monotherapy</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Frequency of dose interruptions</measure>
    <time_frame>At the end of cycle 1 (Each cycle is 21 days)</time_frame>
    <description>Tolerability of RPTR-147:1 in combination with pembrolizumab</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Frequency of dose interruptions</measure>
    <time_frame>At the end of cycle 1 (Each cycle is 21 days)</time_frame>
    <description>Tolerability of RPTR-147:2 in patients with HPV positive tumors</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Best overall response</measure>
    <time_frame>Baseline through approximately 6 months after RPTR-147 last dose as monotherapy and in combination with pembrolizumab</time_frame>
    <description>Per modified RECIST v1.1 (solid tumor) or Lugano classification (lymphoma)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>Baseline through approximately 6 months after RPTR-147 last dose as monotherapy and in combination with pembrolizumab</time_frame>
    <description>Per modified RECIST v1.1 (solid tumor) or Lugano classification (lymphoma)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum observed serum concentration of RPTR-147 as monotherapy and in combination with pembrolizumab</measure>
    <time_frame>Baseline through approximately 1 year</time_frame>
    <description>Maximum observed serum concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the serum concentration-time curve</measure>
    <time_frame>Baseline through approximately 1 year</time_frame>
    <description>Area under the serum concentration-time curve</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunogenicity of RPTR-147 as monotherapy and in combination with pembrolizumab</measure>
    <time_frame>Pre-dose through approximately 1 year after RPTR-147/Pembrolizumab last dose</time_frame>
    <description>Number of subject with anti-RPTR-147/Pembrolizumab antibodies</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">23</enrollment>
  <condition>Solid Tumor</condition>
  <condition>Lymphoma</condition>
  <arm_group>
    <arm_group_label>RPTR-147:1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm A: Escalating doses of RPTR-147:1 as a monotherapy in solid tumors and lymphomas</description>
  </arm_group>
  <arm_group>
    <arm_group_label>RPTR-147:1 and Pembrolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm B: Escalating doses of RPTR-147:1 in combination with Pembrolizumab in patients with solid tumors and lymphomas</description>
  </arm_group>
  <arm_group>
    <arm_group_label>RPTR-147:2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm C: Escalating doses of RPTR-147:2 in patients with HPV-16 positive tumors</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Arm A: RPTR-147:1</intervention_name>
    <description>Escalating doses of RPTR-147:1 as a monotherapy</description>
    <arm_group_label>RPTR-147:1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Arm B: RPTR-147:1 and Pembrolizumab</intervention_name>
    <description>Escalating doses of RPTR-147:1 in combination with Pembrolizumab</description>
    <arm_group_label>RPTR-147:1 and Pembrolizumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Arm C: RPTR-147:2</intervention_name>
    <description>Escalating doses of RPTR-147:2 in patients with HPV positive tumors</description>
    <arm_group_label>RPTR-147:2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        INCLUSION CRITERIA:&#xD;
&#xD;
        Patients eligible for inclusion in this study must meet all of the following criteria:&#xD;
&#xD;
          1. Be willing and able to provide written informed consent for the trial.&#xD;
&#xD;
          2. Written informed consent must be obtained prior to any study procedures.&#xD;
&#xD;
          3. Age ≥18 years (or ≥16 years at Dana Farber Cancer Institute).&#xD;
&#xD;
          4. Histologically- or cytologically-confirmed relapsed/refractory metastatic or&#xD;
             locally-advanced solid tumor or lymphoma whose disease has progressed despite all&#xD;
             appropriate curative or life-prolonging treatments, are intolerant to these therapies&#xD;
             or have refused standard treatment.&#xD;
&#xD;
               1. Inclusion criteria: RPTR-147:1 (Arms A &amp; B) treatment groups&#xD;
&#xD;
                  Cohort enrollment may be limited to potentially immune-responsive tumor types&#xD;
                  meeting the above criterion during the first approximately 2 weeks of the&#xD;
                  enrollment period of each cohort due to their potential to respond to and&#xD;
                  activate RPTR-147:1:&#xD;
&#xD;
                    -  NSCLC&#xD;
&#xD;
                    -  Melanoma&#xD;
&#xD;
                    -  Clear cell cancer of the kidney&#xD;
&#xD;
                    -  HNSCC&#xD;
&#xD;
                    -  Urothelial cancer&#xD;
&#xD;
                    -  Lymphoma&#xD;
&#xD;
                    -  Sarcomas&#xD;
&#xD;
                    -  Ovarian Cancer&#xD;
&#xD;
                    -  Based upon emerging data that will be discussed during the Safety Review&#xD;
                       Committee meetings, the patient population may be further limited based&#xD;
                       other factors&#xD;
&#xD;
               2. Inclusion criteria: RPTR-147:2 (Arm C) treatment group Patients with cancers&#xD;
                  known to be HPV-16 positive.&#xD;
&#xD;
          5. Patient must have documented HLA-typing results that meet the study requirements. The&#xD;
             list of eligible HLA alleles will be updated on an ongoing basis by the Sponsor.&#xD;
&#xD;
             • Once sufficient data has been collected for drug product analytics, or sufficient&#xD;
             HLA coverage is obtained, the HLA-type eligibility requirement may be discontinued by&#xD;
             the Sponsor.&#xD;
&#xD;
          6. For patients with solid tumors, use Response Evaluation Criteria in Solid Tumor&#xD;
             (RECIST) v1.1: measurable disease (at least one measurable non-nodal lesion of at&#xD;
             least 1.0 cm in longest diameter or nodal lesion of at least 1.5 cm in shortest&#xD;
             diameter) documented within 10 weeks of their projected C1D1 visit.&#xD;
&#xD;
             For patients with lymphoma, use the Lugano classification: measurable disease defined&#xD;
             as at least one lesion that can be accurately measured in at least two dimensions with&#xD;
             spiral computed tomography (CT) scan documented within 10 weeks of their projected&#xD;
             C1D1 visit. Minimum measurement must be &gt;15 mm in the longest diameter.&#xD;
&#xD;
             NOTE: If there are no pre-existing radiologic assessments within 10 weeks of the&#xD;
             projected C1D1 visit, other evidence of measurable disease may be considered&#xD;
             sufficient to fulfill this criterion following documented discussion and approval from&#xD;
             the Sponsor.&#xD;
&#xD;
             NOTE: Please note, for dosing/Screening Period 2, patients must have a radiological&#xD;
             assessment per mRECIST v1.1 (solid tumor) or Lugano classification (lymphomas) within&#xD;
             28 days before receiving treatment with RPTR-147 to serve as the patient's baseline&#xD;
             tumor assessment.&#xD;
&#xD;
          7. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1.&#xD;
&#xD;
          8. Have provided archival tumor tissue sample or newly obtained core or excisional&#xD;
             biopsy, during screening period 2, of a tumor lesion not previously irradiated.&#xD;
             Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly&#xD;
             obtained biopsies are preferred to archived tissue. Further details can be found in&#xD;
             the Laboratory Manual.&#xD;
&#xD;
             Note: If submitting unstained cut slides, newly cut slides should be submitted to the&#xD;
             testing laboratory within 14 days from the date slides are cut.&#xD;
&#xD;
          9. RPTR-147:1 in combination with pembrolizumab (Arm B only) - Patients should have&#xD;
             malignancies for which the response rate to anti-PD1/PDL1 monotherapy is &lt;20% or, if&#xD;
             they have malignancies for which anti-PD1/PDL1 are standard of care must have&#xD;
             progressed on treatment with an anti-PD1/L1 monoclonal antibody (mAb) administered&#xD;
             either as monotherapy, or in combination with other checkpoint inhibitors or other&#xD;
             therapies. PD-1 treatment progression is defined by meeting all of the following&#xD;
             criteria:&#xD;
&#xD;
               1. Has received at least 2 doses of an approved anti-PD-1/L1 mAb.&#xD;
&#xD;
               2. Has demonstrated disease progression (PD) after PD-1/L1 as defined by RECIST&#xD;
                  v1.1. The initial evidence of PD is to be confirmed by a second assessment no&#xD;
                  less than four weeks from the date of the first documented PD, in the absence of&#xD;
                  rapid clinical progression.&#xD;
&#xD;
               3. Progressive disease has been documented as per the following within 12 weeks from&#xD;
                  the last dose of anti-PD-1/L1 mAb.&#xD;
&#xD;
         10. A female participant is eligible to participate if she is not pregnant, not&#xD;
             breastfeeding, and at least one of the following conditions applies:&#xD;
&#xD;
               1. Not a woman of childbearing potential (WOCBP)&#xD;
&#xD;
               2. A WOCBP who agrees to follow contraceptive guidance during the treatment period&#xD;
                  and for at least 120 days after the last dose of study treatment.&#xD;
&#xD;
         11. A male participant must agree to use contraception during the treatment period and for&#xD;
             at least 165 days after the last dose of study treatment.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
        Patients eligible for this study must not meet any of the following criteria:&#xD;
&#xD;
          1. Previously identified hypersensitivity to components of RPTR-147 or excipients.&#xD;
&#xD;
          2. Pembrolizumab combination Arm B only - Has severe hypersensitivity (≥Grade 3) to&#xD;
             pembrolizumab and/or any of its excipients.&#xD;
&#xD;
          3. Patients with T-cell lymphomas or small lymphocytic lymphoma.&#xD;
&#xD;
          4. Presence of active central nervous system (CNS) disease and/or carcinomatous&#xD;
             meningitis. Participants with previously treated brain metastases may participate&#xD;
             provided they are radiologically stable, i.e., without evidence of progression for at&#xD;
             least 4 weeks by repeat imaging (note that the repeat imaging should be performed&#xD;
             during study screening), clinically stable, and without requirement of steroid&#xD;
             treatment for at least 14 days prior to first dose of study treatment.&#xD;
&#xD;
          5. Has received prior radiotherapy within 2 weeks of start of study treatment.&#xD;
             Participants must have recovered from all radiation-related toxicities, not require&#xD;
             corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted&#xD;
             for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease. For any&#xD;
             interim radiotherapy received after the baseline tumor assessment, the target lesions&#xD;
             must not be irradiated.&#xD;
&#xD;
          6. Patient having out of range laboratory values defined as:&#xD;
&#xD;
               -  Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) &lt;40&#xD;
                  mL/min&#xD;
&#xD;
               -  Total bilirubin &gt;1.5 x upper limit of normal (ULN), except for patients with&#xD;
                  Gilbert's syndrome who are excluded if total bilirubin &gt;3.0 x ULN or direct&#xD;
                  bilirubin &gt;1.5 x ULN&#xD;
&#xD;
               -  Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) &gt;3 x ULN,&#xD;
                  except for patients that have tumor involvement of the liver, who are excluded if&#xD;
                  ALT &gt;5 x ULN&#xD;
&#xD;
               -  Absolute neutrophil count ≤1.0 x 109/L&#xD;
&#xD;
               -  ≥0.5 x 109/L and increasing following prior myelosuppressive treatment will be&#xD;
                  eligible&#xD;
&#xD;
               -  Screening Period 1 Only: Absolute lymphocyte count ≤1.0 x 109/L for solid tumor&#xD;
                  patients or ≤7.0 x 108/L for lymphoma patients prior to the apheresis procedure.&#xD;
&#xD;
               -  Platelet count ≤75 x 109/L absent platelet transfusion for 2 weeks&#xD;
&#xD;
               -  Hemoglobin (Hgb) ≤9 g/dL absent RBC transfusion for 2 weeks&#xD;
&#xD;
               -  ≥8 g/dL and increasing following prior myelosuppressive treatment will be&#xD;
                  eligible&#xD;
&#xD;
               -  Coagulation (prothrombin time [PT] or international normalized ratio [INR] and&#xD;
                  partial thromboplastin time [PTT] or activated partial thromboplastin time&#xD;
                  [aPTT])&#xD;
&#xD;
               -  &gt;1.5 × ULN unless participant is receiving anticoagulant therapy as long as&#xD;
                  PT/INR and PTT/aPTT is within therapeutic range of intended use of anticoagulants&#xD;
&#xD;
               -  Potassium, magnesium, calcium or phosphate abnormality &gt; CTCAE v5.0 Grade 1&#xD;
                  despite appropriate oral replacement therapy&#xD;
&#xD;
               -  Screening Period 1 Only: Serum triglycerides &gt;500 mg/dL due to potential&#xD;
                  interference with cell separation methods&#xD;
&#xD;
          7. Impaired cardiac function or clinically significant cardiac disease, including any of&#xD;
             the following:&#xD;
&#xD;
               -  Clinically significant and/or uncontrolled heart disease such as congestive heart&#xD;
                  failure requiring treatment (New York Heart Association [NYHA] Grade ≥2),&#xD;
                  uncontrolled hypertension, or clinically significant arrhythmia&#xD;
&#xD;
               -  Acute myocardial infarction or unstable angina pectoris &lt;6 months prior to study&#xD;
                  entry&#xD;
&#xD;
          8. Patients with active, known or suspected autoimmune disease that has required systemic&#xD;
             treatment in the past 2 years (i.e., with use of disease modifying agents,&#xD;
             corticosteroids, or immunosuppressive drugs).&#xD;
&#xD;
               1. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid&#xD;
                  replacement therapy for adrenal or pituitary insufficiency) is not considered a&#xD;
                  form of systemic treatment and is allowed.&#xD;
&#xD;
               2. Patients with vitiligo, type 1 diabetes mellitus, residual hypothyroidism due to&#xD;
                  autoimmune condition only requiring hormone replacement, psoriasis not requiring&#xD;
                  systemic treatment, or conditions not expected to recur in the absence of an&#xD;
                  external trigger are permitted to enroll.&#xD;
&#xD;
          9. Has a history of (non-infectious) pneumonitis that required steroids or has current&#xD;
             pneumonitis.&#xD;
&#xD;
         10. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy&#xD;
             (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of&#xD;
             immunosuppressive therapy within 7 days prior to the first dose of study drug.&#xD;
&#xD;
         11. Has a known additional malignancy that is progressing or has required active treatment&#xD;
             within the past 3 years.&#xD;
&#xD;
             Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of&#xD;
             the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that&#xD;
             have undergone potentially curative therapy are not excluded.&#xD;
&#xD;
         12. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is&#xD;
             required unless mandated by local health authority.&#xD;
&#xD;
         13. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]&#xD;
             reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is&#xD;
             detected) infection.&#xD;
&#xD;
             Note: No testing for Hepatitis B and Hepatitis C is required unless mandated by local&#xD;
             health authority.&#xD;
&#xD;
         14. Malignant disease, other than that being treated in this study expected to interfere&#xD;
             with the assessment of efficacy in the opinion of the investigator.&#xD;
&#xD;
         15. Active infection requiring systemic therapy.&#xD;
&#xD;
         16. Patients requiring chronic treatment with systemic steroid therapy, other than&#xD;
             replacement dose steroids in the setting of adrenal insufficiency. Topical, inhaled,&#xD;
             nasal, or ophthalmic steroids are allowed.&#xD;
&#xD;
         17. Patients receiving systemic treatment with any immunosuppressive medication.&#xD;
&#xD;
         18. Use of any live vaccines against infectious diseases within 30 days of initiation of&#xD;
             study treatment. Examples of live vaccines include, but are not limited to, the&#xD;
             following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever,&#xD;
             rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza&#xD;
             vaccines for injection are generally killed virus vaccines and are allowed; however,&#xD;
             intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are&#xD;
             not allowed.&#xD;
&#xD;
         19. Major surgery within 4 weeks of the first dose of study treatment (mediastinoscopy,&#xD;
             insertion of a central venous access device, and insertion of a feeding tube are not&#xD;
             considered major surgery).&#xD;
&#xD;
             Note: If participant received major surgery, they must have recovered adequately from&#xD;
             the toxicity and/or complications from the intervention prior to starting study&#xD;
             treatment.&#xD;
&#xD;
         20. Is currently participating in or has participated in a study of an investigational&#xD;
             agent or has used an investigational device within 4 weeks prior to the first dose of&#xD;
             study treatment.&#xD;
&#xD;
             Note: Patients who have entered the follow-up phase of another investigational study&#xD;
             may participate in this study as long as it has been 4 weeks after the last dose of&#xD;
             the previous investigational agent.&#xD;
&#xD;
             Note: Patients may participate in other local biomarker studies following documented&#xD;
             discussion and approval from Repertoire Immune Medicines.&#xD;
&#xD;
             Note: T-cell imaging agents may be permitted following documented discussion and&#xD;
             approval with the Sponsor.&#xD;
&#xD;
         21. Presence of ≥CTCAE v5.0 Grade 2 toxicity from prior therapy (except alopecia,&#xD;
             peripheral neuropathy, and ototoxicity, which are excluded if ≥CTCAE v5.0 Grade 3) due&#xD;
             to prior cancer treatment.&#xD;
&#xD;
         22. Initiation of hematopoietic colony-stimulating growth factors (e.g. Granulocyte Colony&#xD;
             Stimulating Factor [G-CSF], Granulocyte Macrophage Colony Stimulating Factor [GMCSF],&#xD;
             Macrophage Colony Stimulating Factor [M-CSF]) ≤2 weeks prior to start of study drug.&#xD;
             An erythroid stimulating agent is allowed as long as it was initiated at least 2 weeks&#xD;
             prior to the first dose of study treatment.&#xD;
&#xD;
         23. An unresolved AE (must be ≤Grade 1 or the patient's baseline).&#xD;
&#xD;
         24. Prior treatment with CAR-T-cell therapy.&#xD;
&#xD;
         25. Has undergone prior allogeneic HSCT&#xD;
&#xD;
         26. RPTR-147 Monotherapy: Patients who were required to discontinue PD-1/PD-L1, CTLA-4, or&#xD;
             other immunomodulatory antibodies due to ≥Grade 3 irAE may be included following&#xD;
             discussion with the Sponsor.&#xD;
&#xD;
         27. RPTR-147:1 in Combination with pembrolizumab: Has received prior therapy with an&#xD;
             anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another&#xD;
             stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137) and was&#xD;
             discontinued from that treatment due to a Grade 3 or higher irAE.&#xD;
&#xD;
         28. Patients with a history of &gt;3 lines of chemotherapy in the metastatic setting may be&#xD;
             eligible for enrollment following discussion with the Sponsor.&#xD;
&#xD;
         29. Patients with a history of rapidly progressing disease on immunotherapy.&#xD;
&#xD;
               1. Prior clinical or radiological disease progression (excluding pseudoprogression)&#xD;
                  within 8 weeks after starting prior immunotherapy with PD-1/PDL-1, CTLA-4&#xD;
                  inhibitors.&#xD;
&#xD;
               2. These patients may only be enrolled following discussion with the Sponsor to&#xD;
                  account for manufacturing time.&#xD;
&#xD;
         30. Prior therapy with PD-1/PDL-1, CTLA-4 or other immunomodulatory antibodies inhibitors:&#xD;
&#xD;
               1. ≤2 weeks prior to the apheresis procedure&#xD;
&#xD;
               2. ≤4 weeks prior to the first dose of study treatment&#xD;
&#xD;
         31. Systemic anti-cancer therapy within 5 half-lives or 2 weeks; whichever occurs first,&#xD;
             of the apheresis procedure and the first dose of study treatment.&#xD;
&#xD;
               1. Systemic cytotoxic agents that have major delayed toxicity, e.g. mitomycin C and&#xD;
                  nitrosoureas, ≤6 weeks prior to the first dose of study treatment&#xD;
&#xD;
               2. Participants must have recovered from all AEs due to previous therapies to ≤Grade&#xD;
                  1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.&#xD;
&#xD;
         32. Has a history or current evidence of any condition, therapy, or laboratory abnormality&#xD;
             that might confound the results of the study, interfere with the participant's&#xD;
             participation for the full duration of the study, or is not in the best interest of&#xD;
             the participant to participate, in the opinion of the treating investigator.&#xD;
&#xD;
         33. Has known psychiatric or substance abuse disorders that would interfere with&#xD;
             cooperating with the requirements of the study.&#xD;
&#xD;
         34. Is pregnant or breastfeeding or expecting to conceive or father children within the&#xD;
             projected duration of the study, starting with the screening visit through 150 days&#xD;
             after the last dose of study treatment.&#xD;
&#xD;
         35. Women of childbearing potential (WOCBP), defined as all women physiologically capable&#xD;
             of becoming pregnant, unless they are using highly effective methods of contraception&#xD;
             during study treatment and for 120 days after the last dose of study treatment. Highly&#xD;
             effective contraception methods include:&#xD;
&#xD;
               1. Female sterilization, total hysterectomy, or tubal ligation at least 6 weeks&#xD;
                  before taking study treatment.&#xD;
&#xD;
               2. Male sterilization (at least 6 months prior to screening). For female patients on&#xD;
                  the study the vasectomized male partner should be the sole partner for that&#xD;
                  patient.&#xD;
&#xD;
               3. Use of oral (estrogen and progesterone), injected or implanted combined hormonal&#xD;
                  methods of contraception or placement of an intrauterine device (IUD) or&#xD;
                  intrauterine system (IUS) or other forms of hormonal contraception that have&#xD;
                  comparable efficacy (failure rate &lt;1%), for example, hormone vaginal ring or&#xD;
                  transdermal hormone contraception.&#xD;
&#xD;
             In case of use of oral contraception, women should have been stable on the same pill&#xD;
             for a minimum of 3 months before taking study treatment.&#xD;
&#xD;
             Women are considered post-menopausal and not of childbearing potential if they have&#xD;
             had 12 months of natural amenorrhea with an appropriate clinical profile or have had&#xD;
             surgical bilateral oophorectomy or tubal ligation at least 6 weeks prior to the first&#xD;
             dose of study treatment.&#xD;
&#xD;
         36. A WOCBP who has a positive urine pregnancy test (e.g. within 72 hours) prior to&#xD;
             treatment. If the urine test is positive or cannot be confirmed as negative, a serum&#xD;
             pregnancy test will be required.&#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>David Spriggs, MD</last_name>
    <role>Study Director</role>
    <affiliation>Repertoire Immune Medicines</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>City of Hope</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yale Cancer Center</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06511</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>Karmanos Cancer Institute</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carolina BioOncology Institute</name>
      <address>
        <city>Huntersville</city>
        <state>North Carolina</state>
        <zip>28078</zip>
        <country>United States</country>
      </address>
    </facility>
  </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>
  </location>
  <location>
    <facility>
      <name>MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</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>January 14, 2019</study_first_submitted>
  <study_first_submitted_qc>January 23, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 24, 2019</study_first_posted>
  <last_update_submitted>December 2, 2022</last_update_submitted>
  <last_update_submitted_qc>December 2, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 6, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HPV-16 E6/E7 positive solid tumors</keyword>
  <keyword>Melanoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</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/NCT03815682
org study id: TT-101
secondary id: KEYNOTE KN-948
nct id: NCT03815682
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to assess the safety and tolerability of escalating doses of
      RPTR-147 as a monotherapy and in combination with Pembrolizumab in patients with selected
      solid tumors and lymphomas.
This is a first-in-human, open-label, multicenter, dose escalation study designed to
      determine the safety and tolerability of RPTR-147 as a monotherapy and in combination with
      Pembrolizumab in patients with selected solid tumors or lymphomas.

      The study will include 2 dosing periods: A Dose Escalation (Phase 1) followed by an Expansion
      (Phase 2).
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of subjects with dose limiting toxicities
time frame: At the end of cycle 1 (Each cycle is 28 days)
description: Safety of RPTR-147:1 as a monotherapy
measure: Number of subjects with dose limiting toxicities
time frame: At the end of cycle 1 (Each cycle is 21 days)
description: Safety of RPTR-147:1 in combination with pembrolizumab
measure: Number of subjects with dose limiting toxicities
time frame: At the end of cycle 1 (Each cycle is 21 days)
description: Safety of RPTR-147:2 as a monotherapy
measure: Frequency of dose interruptions
time frame: At the end of cycle 1 (Each cycle is 28 days)
description: Tolerability of RPTR-147:1 as a monotherapy
measure: Frequency of dose interruptions
time frame: At the end of cycle 1 (Each cycle is 21 days)
description: Tolerability of RPTR-147:1 in combination with pembrolizumab
measure: Frequency of dose interruptions
time frame: At the end of cycle 1 (Each cycle is 21 days)
description: Tolerability of RPTR-147:2 in patients with HPV positive tumors
measure: Best overall response
time frame: Baseline through approximately 6 months after RPTR-147 last dose as monotherapy and in combination with pembrolizumab
description: Per modified RECIST v1.1 (solid tumor) or Lugano classification (lymphoma)
measure: Progression free survival
time frame: Baseline through approximately 6 months after RPTR-147 last dose as monotherapy and in combination with pembrolizumab
description: Per modified RECIST v1.1 (solid tumor) or Lugano classification (lymphoma)
measure: Maximum observed serum concentration of RPTR-147 as monotherapy and in combination with pembrolizumab
time frame: Baseline through approximately 1 year
description: Maximum observed serum concentration
measure: Area under the serum concentration-time curve
time frame: Baseline through approximately 1 year
description: Area under the serum concentration-time curve
measure: Immunogenicity of RPTR-147 as monotherapy and in combination with pembrolizumab
time frame: Pre-dose through approximately 1 year after RPTR-147/Pembrolizumab last dose
description: Number of subject with anti-RPTR-147/Pembrolizumab antibodies
arm group label: RPTR-147:1
arm group type: Experimental
description: Arm A: Escalating doses of RPTR-147:1 as a monotherapy in solid tumors and lymphomas
arm group label: RPTR-147:1 and Pembrolizumab
arm group type: Experimental
description: Arm B: Escalating doses of RPTR-147:1 in combination with Pembrolizumab in patients with solid tumors and lymphomas
arm group label: RPTR-147:2
arm group type: Experimental
description: Arm C: Escalating doses of RPTR-147:2 in patients with HPV-16 positive tumors
intervention type: Biological
intervention name: Arm A: RPTR-147:1
description: Escalating doses of RPTR-147:1 as a monotherapy
arm group label: RPTR-147:1
intervention type: Biological
intervention name: Arm B: RPTR-147:1 and Pembrolizumab
description: Escalating doses of RPTR-147:1 in combination with Pembrolizumab
arm group label: RPTR-147:1 and Pembrolizumab
intervention type: Biological
intervention name: Arm C: RPTR-147:2
description: Escalating doses of RPTR-147:2 in patients with HPV positive tumors
arm group label: RPTR-147:2
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: David Spriggs, MD
role: Study Director
affiliation: Repertoire Immune Medicines
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Pembrolizumab
sharing ipd: No