xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06022029</url>
    </required_header>
    <id_info>
      <org_study_id>ON-5001</org_study_id>
      <nct_id>NCT06022029</nct_id>
    </id_info>
    <brief_title>A Dose Escalation and Dose Expansion Study of Intratumoral ONM-501 Alone and in Combination With Cemiplimab in Patients With Advanced Solid Tumors and Lymphomas.</brief_title>
    <acronym>ON-5001</acronym>
    <official_title>A Phase 1 Dose-Escalation and Expansion Study of Intratumorally Administered ONM-501 Alone and in Combination With Cemiplimab in Patients With Advanced Solid Tumors and Lymphomas</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>OncoNano Medicine, Inc.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>OncoNano Medicine, Inc.</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>
        A phase 1, multicenter, open label, non-randomized dose escalation and dose expansion study&#xD;
        to examine the maximum tolerated dose, (MTD), minimum effective dose (MED) and/or recommended&#xD;
        dose for expansion (RDE) of intratumoral ONM-501 as monotherapy and in combination with a&#xD;
        PD-1 checkpoint inhibitor in patients with advanced solid tumors and lymphomas.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This Phase 1, multi-center trial will consist of three parts: monotherapy dose escalation;&#xD;
        combination therapy dose finding; and combination therapy dose expansion exploring two doses&#xD;
        in specific tumor indication(s). Each dosing cycle of ONM-501 will be 21 days. ONM 501 will&#xD;
        be administered as intratumoral injections once per week for three weeks (on Days 1, 8, and&#xD;
        15), followed by three weeks without ONM-501 administration. The monotherapy dose escalation&#xD;
        will utilize an accelerated titration method.&#xD;
  &#xD;
        The combination agent will be administered according to standard protocol, once every three&#xD;
        weeks. This phase will evaluate ONM-501 in combination with approved immune checkpoint&#xD;
        inhibitor (ICI) cemiplimab. Enrollment in this phase will follow a &quot;Rolling 6&quot; or 6+0&#xD;
        methodology - up to 6 patients will be enrolled in a staggered format; dose escalation of&#xD;
        ONM-501 will be permitted.&#xD;
  &#xD;
        Once the recommended doses for expansion (RDEs) are determined for ONM-501 + ICI combination&#xD;
        or ONM-501 monotherapy, the expansion phase of this study will be initiated. The expansion&#xD;
        phase will enroll patients in one to three indication-specific expansion cohorts.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 29, 2023</start_date>
    <completion_date type="Anticipated">August 29, 2026</completion_date>
    <primary_completion_date type="Anticipated">April 30, 2026</primary_completion_date>
    <phase>Phase 1</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>In Part 1a patients will receive ONM-501 as a single agent; in Part 1b patients will receive ONM-501 in combination with Cemiplimab; Part 2 will be an expansion of ONM-501 in combination with Cemiplimab.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Dose Escalation and Expansion Phases: Number of Participants Reporting one or More Treatment-emergent Adverse Events (TEAEs) and Based on TEAEs Severity</measure>
      <time_frame>Up to approximately 24 months</time_frame>
      <description>AE incidence will be coded using Medical Dictionary for Regulatory Activities (MedDRA) terminology. AE severity will be graded according to NCI CTCAE version 5.0 or later. Grade 1 scales as Mild (asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated); Grade 2 scales as Moderate (minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living [ADL]); Grade 3 scales as Severe (severe or medically significant but not immediately life threatening hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL); Grade 4 scales as Life-threatening consequences, urgent intervention indicated, and Grade 5 scales as Death related to Adverse Event (AE)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Dose Escalation and Expansion Phases: Number of Participants with Dose-Limiting Toxicities (DLTs)</measure>
      <time_frame>Up to approximately 24 months</time_frame>
      <description>DLT will be defined as the occurrence of any of the following events in the first 28 days of treatment in the dose escalation cohorts in Part 1 of the study or in the first 28 days of treatment for the first 6 patients at any dose in Part 1b (DLT observation periods). Any adverse event resulting in a dose hold or delay of ≥ 28 days will be considered a DLT. Toxicity will be evaluated according to NCI CTCAE version 5.0.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Dose Escalation and Expansion Phases: Number of Participants Reporting One or More Treatment Emergent Serious Adverse Event (SAEs)</measure>
      <time_frame>Up to approximately 24 months</time_frame>
      <description>AE incidence will be coded using Medical Dictionary for Regulatory Activities (MedDRA) terminology. AE severity will be graded according to NCI CTCAE version 5.0 or later.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation and Expansion Phases: Cmax</measure>
      <time_frame>Dose Escalation and Expansion Phases: Cycle 1 Day 1 and Cycle 1 Day 8 (each cycle is 21 days): predose and at multiple timepoints (up to 24 hours).</time_frame>
      <description>Cmax is defined as the Maximum Observed Plasma Concentration for ONM-501</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation and Expansion Phases: t1/2z</measure>
      <time_frame>Dose Escalation and Expansion Phases: Cycle 1 Day 1 and Cycle 1 Day 8 (each cycle is 21 days): predose and at multiple timepoints (up to 24 hours).</time_frame>
      <description>t1/2z is defined as the Terminal Disposition Phase Half-life for ONM-501</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation and Expansion Phases: Tmax</measure>
      <time_frame>Dose Escalation and Expansion Phases: Cycle 1 Day 1 and Cycle 1 Day 8 (each cycle is 21 days): predose and at multiple timepoints (up to 24 hours).</time_frame>
      <description>Tmax is defined as the Time to Reach the Maximum Plasma Concentration (Cmax) for ONM-501</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation and Expansion Phases: AUCt</measure>
      <time_frame>Dose Escalation and Expansion Phases: Cycle 1 Day 1 and Cycle 1 Day 8 (each cycle is 21 days): predose and at multiple timepoints (up to 24 hours).</time_frame>
      <description>AUCt is defined as the Area Under the Concentration-time Curve from Time 0 to Time t for ONM-501</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation and Expansion Phases: AUCinf</measure>
      <time_frame>Dose Escalation and Expansion Phases: Cycle 1 Day 1 and Cycle 1 Day 8 (each cycle is 21 days): predose and at multiple timepoints (up to 24 hours).</time_frame>
      <description>AUCinf is defined as the Area Under the Concentration-time Curve from Time 0 to Infinity for ONM-501</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation and Expansion Phases: CL/F</measure>
      <time_frame>Dose Escalation and Expansion Phases: Cycle 1 Day 1 and Cycle 1 Day 8 (each cycle is 21 days): predose and at multiple timepoints (up to 24 hours).</time_frame>
      <description>CL/F is defined as the apparent clearance of ONM-501 (CL/F), where F is the fraction of the dose absorbed.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation and Expansion Phases: Vz/F</measure>
      <time_frame>Dose Escalation and Expansion Phases: Cycle 1 Day 1 and Cycle 1 Day 8 (each cycle is 21 days): predose and at multiple timepoints (up to 24 hours).</time_frame>
      <description>Vz/F is defined as the apparent volume of distribution of ONM-501 (CL/F), where F is the fraction of the dose absorbed.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Expansion Phase Only: Objective Response Rate (ORR)</measure>
      <time_frame>Up to approximately 24 months</time_frame>
      <description>Objective response will be defined as a best response of CR or PR. The objective response rate (ORR) will be calculated as the proportion of patients in the Efficacy Analysis Set who achieve an objective response. ORR will be assessed based on Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1.&#xD;
  Characterize the plasma pharmacokinetics (PK) of IT ONM-501 as monotherapy and in combination with cemiplimab&#xD;
  Evaluate additional measures of clinical benefit including: Duration of Response (DOR), Progression Free Survival (PFS) by RECIST and Overall Survival</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Expansion Phase Only: Duration of Response (DOR)</measure>
      <time_frame>Up to approximately 24 months</time_frame>
      <description>DOR analyses will be conducted for those patients in the Efficacy Analysis Set who achieve an objective response and is defined as the time from first objective status assessment of CR or PR until documentation of objective disease progression or death from any cause. Patients who do not progress and do not die will be censored on the date of last adequate tumor assessment. If no further adequate post-treatment tumor assessments were obtained for a patient, DOR will be censored at the date of the objective response (i.e., zero duration). DOR will be assessed based on RECIST v1.1.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Expansion Phase Only: Progression-Free Survival (PFS)</measure>
      <time_frame>Up to approximately 24 months</time_frame>
      <description>PFS is defined as the time from administration of the first dose of ONM-501 until documentation of objective disease progression or death from any cause. Patients who do not progress and do not die will be censored on the date of last adequate tumor assessment. If no adequate post treatment tumor assessments were obtained for a patient, PFS will be censored at Day 1 (i.e., zero duration). The PFS analysis will be conducted using the Safety Analysis Set.&#xD;
  Assess the biological effects of IT ONM-501 demonstrated by changes in immune cells, immune cell markers, serum cytokines (such as TNF-⍺, IFN-⍺, IFN-β, and others consistent with activation of the cGAS-STING pathway) and gene expression patterns</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Expansion Phase Only: Overall Survival (OS)</measure>
      <time_frame>Up to approximately 24 months</time_frame>
      <description>OS is defined as the time from the date of first dose administration to the date of death.</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">168</enrollment>
    <condition>Triple Negative Breast Cancer</condition>
    <condition>Diffuse Large B Cell Lymphoma</condition>
    <condition>Follicular Lymphoma</condition>
    <condition>Lymphoma, Non-Hodgkin</condition>
    <condition>Mantle Cell Lymphoma</condition>
    <condition>Bladder Cancer</condition>
    <condition>Uveal Melanoma, Recurrent</condition>
    <condition>Cervix Cancer</condition>
    <condition>Carcinoma in Situ</condition>
    <condition>Head and Neck Squamous Cell Carcinoma</condition>
    <condition>Skin Cancer</condition>
    <condition>Metastatic Cancer</condition>
    <condition>Tumor, Solid</condition>
    <condition>Tumor Recurrence</condition>
    <arm_group>
      <arm_group_label>Part 1a: Monotherapy Dose Escalation</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>ONM-501 will be administered as intratumoral injections once per week for three weeks, followed by three weeks without ONM-501 administration. Each dosing cycle will be 21 days.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Part 1b: ONM-501 in Combination with cemiplimab</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>ONM-501 will be administered as intratumoral injections once per week for three weeks followed by three weeks without ONM-501 administration. Each dosing cycle will be 21 days. The combination agent will be administered according to standard protocol, once every three weeks.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Part 2: RDE ONM-501 in Combination with cemiplimab in indication-specific expansion cohorts</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Once the recommended doses for expansion (RDEs) are determined for ONM-501 + ICI combination or ONM-501 monotherapy, the expansion phase of the study will be initiated. The expansion phase will enroll patients in one to three indication-specific expansion cohorts.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>ONM-501</intervention_name>
      <description>Intratumoral injection</description>
      <arm_group_label>Part 1a: Monotherapy Dose Escalation</arm_group_label>
      <arm_group_label>Part 1b: ONM-501 in Combination with cemiplimab</arm_group_label>
      <arm_group_label>Part 2: RDE ONM-501 in Combination with cemiplimab in indication-specific expansion cohorts</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Cemiplimab</intervention_name>
      <description>Intravenous administration of 350 mg</description>
      <arm_group_label>Part 1b: ONM-501 in Combination with cemiplimab</arm_group_label>
      <arm_group_label>Part 2: RDE ONM-501 in Combination with cemiplimab in indication-specific expansion cohorts</arm_group_label>
      <other_name>Libtayo</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Ability to understand and willingness to sign written informed consent before&#xD;
               performance of any study procedures&#xD;
  &#xD;
            2. Age ≥ 18 years&#xD;
  &#xD;
            3. Participants with solid tumors or lymphomas, confirmed by available histopathology&#xD;
               records or current biopsy, that are advanced, nonresectable, or recurrent and&#xD;
               progressing since last antitumor therapy, and for which no alternative standard&#xD;
               therapy exists.&#xD;
  &#xD;
            4. Participants must have a minimum of one injectable and measurable lesion.&#xD;
  &#xD;
            5. Participants with prior Hepatitis B or C are eligible if they have adequate liver&#xD;
               function&#xD;
  &#xD;
            6. Participants with human immunodeficiency virus (HIV) are eligible if on established&#xD;
               HAART for a minimum of 4 weeks prior to enrollment, have an HIV viral load &lt;400&#xD;
               copies/mL, and have CD4+ T-cell (CD4+) counts ≥ 350 cells/uL&#xD;
  &#xD;
            7. Adequate bone marrow function:&#xD;
  &#xD;
            8. Adequate liver function&#xD;
  &#xD;
          Exclusion Criteria: Patients will be excluded from this study if they meet any of the&#xD;
          following criteria (Part 1a and Part 1b).&#xD;
  &#xD;
            1. Other malignancy active within the previous 2 years except for basal or squamous cell&#xD;
               skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast&#xD;
               that has completed curative therapy.&#xD;
  &#xD;
            2. Major surgery within 4 weeks before the first dose of study drug.&#xD;
  &#xD;
            3. Brain metastases that are untreated or in the posterior fossa or involve the meninges.&#xD;
               Participants with stable or previously treated progressing brain metastases (except in&#xD;
               the posterior fossa or involving the meninges) may be permitted in a case-by-case&#xD;
               basis at the Sponsor's discretion.&#xD;
  &#xD;
            4. Prolongation of corrected QT (QTc) interval to &gt;470 millisecond (ms) for males and&#xD;
               females when electrolytes balance is normal.&#xD;
  &#xD;
            5. Females who are breastfeeding or pregnant at screening or baseline&#xD;
  &#xD;
            6. Females of childbearing potential that refuse to use a highly effective method of&#xD;
               contraception.&#xD;
  &#xD;
            7. Has uncontrolled or poorly controlled hypertension as defined by a sustained BP &gt; 9.&#xD;
               Has received prior investigational therapy within 5 half-lives of the agent or 4 weeks&#xD;
               before the first administration of study drug, whichever is shorter.&#xD;
  &#xD;
            8. Has had any major cardiovascular event within 6 months prior to study drug 10. Has&#xD;
               known hypersensitivity to any component in the formulation of ONM-501&#xD;
  &#xD;
            9. Has an active infection requiring systemic treatment&#xD;
  &#xD;
           10. Is participating in another therapeutic clinical trial&#xD;
  &#xD;
          Additional Exclusion Criteria for ONM-501 in Combination with cemiplimab (Part 1b)&#xD;
  &#xD;
            1. Has known hypersensitivity to any component in the formulation of cemiplimab&#xD;
  &#xD;
            2. Has any active or recent history of a known or suspected autoimmune disease or recent&#xD;
               history of a syndrome that required systemic corticosteroids (&gt;10 mg daily prednisone&#xD;
               equivalent)&#xD;
  &#xD;
            3. Has a condition requiring systemic treatment with corticosteroids&#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_contact>
      <last_name>Trials@OncoNanoMed.com</last_name>
      <phone>(682) 285-1411</phone>
      <email>trials@onconanomed.com</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 15, 2023</study_first_submitted>
    <study_first_submitted_qc>August 29, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 1, 2023</study_first_posted>
    <last_update_submitted>August 29, 2023</last_update_submitted>
    <last_update_submitted_qc>August 29, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Solid tumors</keyword>
    <keyword>Lymphoma</keyword>
    <keyword>ONM-501</keyword>
    <keyword>STING</keyword>
    <keyword>Intra-tumoral</keyword>
    <keyword>HNSCC</keyword>
    <keyword>Breast Cancer</keyword>
    <keyword>Melanoma</keyword>
    <keyword>Skin Cancer</keyword>
    <keyword>cemiplimab</keyword>
    <keyword>Libtayo</keyword>
    <keyword>DLBCL</keyword>
    <keyword>bladder cancer</keyword>
    <keyword>cervical cancer</keyword>
    <keyword>metastases</keyword>
    <keyword>immunotherapy</keyword>
    <keyword>ICI</keyword>
    <keyword>TNBC</keyword>
    <keyword>Triple Negative</keyword>
    <keyword>mTNBC</keyword>
    <keyword>anti-PD-1 antibody</keyword>
    <keyword>BRCA1</keyword>
    <keyword>BRCA2</keyword>
    <keyword>anti-PD-L1</keyword>
    <keyword>uveal</keyword>
    <keyword>NHL</keyword>
    <keyword>Mantle Zone lymphoma</keyword>
    <keyword>FL</keyword>
    <keyword>stimulator of interferon genes</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Lymphoma</mesh_term>
      <mesh_term>Carcinoma</mesh_term>
      <mesh_term>Neoplasms</mesh_term>
      <mesh_term>Melanoma</mesh_term>
      <mesh_term>Urinary Bladder Neoplasms</mesh_term>
      <mesh_term>Lymphoma, Mantle-Cell</mesh_term>
      <mesh_term>Lymphoma, Large B-Cell, Diffuse</mesh_term>
      <mesh_term>Triple Negative Breast Neoplasms</mesh_term>
      <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
      <mesh_term>Skin Neoplasms</mesh_term>
      <mesh_term>Carcinoma in Situ</mesh_term>
      <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
      <mesh_term>Uterine Cervical 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>Cemiplimab</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06022029
  org study id: ON-5001
  nct id: NCT06022029
  lead sponsor: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: No
  A phase 1, multicenter, open label, non-randomized dose escalation and dose expansion study
        to examine the maximum tolerated dose, (MTD), minimum effective dose (MED) and/or recommended
        dose for expansion (RDE) of intratumoral ONM-501 as monotherapy and in combination with a
        PD-1 checkpoint inhibitor in patients with advanced solid tumors and lymphomas.
  This Phase 1, multi-center trial will consist of three parts: monotherapy dose escalation;
        combination therapy dose finding; and combination therapy dose expansion exploring two doses
        in specific tumor indication(s). Each dosing cycle of ONM-501 will be 21 days. ONM 501 will
        be administered as intratumoral injections once per week for three weeks (on Days 1, 8, and
        15), followed by three weeks without ONM-501 administration. The monotherapy dose escalation
        will utilize an accelerated titration method.
  
        The combination agent will be administered according to standard protocol, once every three
        weeks. This phase will evaluate ONM-501 in combination with approved immune checkpoint
        inhibitor (ICI) cemiplimab. Enrollment in this phase will follow a "Rolling 6" or 6+0
        methodology - up to 6 patients will be enrolled in a staggered format; dose escalation of
        ONM-501 will be permitted.
  
        Once the recommended doses for expansion (RDEs) are determined for ONM-501 + ICI combination
        or ONM-501 monotherapy, the expansion phase of this study will be initiated. The expansion
        phase will enroll patients in one to three indication-specific expansion cohorts.
  allocation: Non-Randomized
  intervention model: Sequential Assignment
  intervention model description: In Part 1a patients will receive ONM-501 as a single agent; in Part 1b patients will receive ONM-501 in combination with Cemiplimab; Part 2 will be an expansion of ONM-501 in combination with Cemiplimab.
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Dose Escalation and Expansion Phases: Number of Participants Reporting one or More Treatment-emergent Adverse Events (TEAEs) and Based on TEAEs Severity
  time frame: Up to approximately 24 months
  description: AE incidence will be coded using Medical Dictionary for Regulatory Activities (MedDRA) terminology. AE severity will be graded according to NCI CTCAE version 5.0 or later. Grade 1 scales as Mild (asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated); Grade 2 scales as Moderate (minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living [ADL]); Grade 3 scales as Severe (severe or medically significant but not immediately life threatening hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL); Grade 4 scales as Life-threatening consequences, urgent intervention indicated, and Grade 5 scales as Death related to Adverse Event (AE)
  measure: Dose Escalation and Expansion Phases: Number of Participants with Dose-Limiting Toxicities (DLTs)
  time frame: Up to approximately 24 months
  description: DLT will be defined as the occurrence of any of the following events in the first 28 days of treatment in the dose escalation cohorts in Part 1 of the study or in the first 28 days of treatment for the first 6 patients at any dose in Part 1b (DLT observation periods). Any adverse event resulting in a dose hold or delay of ≥ 28 days will be considered a DLT. Toxicity will be evaluated according to NCI CTCAE version 5.0.
  measure: Dose Escalation and Expansion Phases: Number of Participants Reporting One or More Treatment Emergent Serious Adverse Event (SAEs)
  time frame: Up to approximately 24 months
  description: AE incidence will be coded using Medical Dictionary for Regulatory Activities (MedDRA) terminology. AE severity will be graded according to NCI CTCAE version 5.0 or later.
  measure: Dose Escalation and Expansion Phases: Cmax
  time frame: Dose Escalation and Expansion Phases: Cycle 1 Day 1 and Cycle 1 Day 8 (each cycle is 21 days): predose and at multiple timepoints (up to 24 hours).
  description: Cmax is defined as the Maximum Observed Plasma Concentration for ONM-501
  measure: Dose Escalation and Expansion Phases: t1/2z
  time frame: Dose Escalation and Expansion Phases: Cycle 1 Day 1 and Cycle 1 Day 8 (each cycle is 21 days): predose and at multiple timepoints (up to 24 hours).
  description: t1/2z is defined as the Terminal Disposition Phase Half-life for ONM-501
  measure: Dose Escalation and Expansion Phases: Tmax
  time frame: Dose Escalation and Expansion Phases: Cycle 1 Day 1 and Cycle 1 Day 8 (each cycle is 21 days): predose and at multiple timepoints (up to 24 hours).
  description: Tmax is defined as the Time to Reach the Maximum Plasma Concentration (Cmax) for ONM-501
  measure: Dose Escalation and Expansion Phases: AUCt
  time frame: Dose Escalation and Expansion Phases: Cycle 1 Day 1 and Cycle 1 Day 8 (each cycle is 21 days): predose and at multiple timepoints (up to 24 hours).
  description: AUCt is defined as the Area Under the Concentration-time Curve from Time 0 to Time t for ONM-501
  measure: Dose Escalation and Expansion Phases: AUCinf
  time frame: Dose Escalation and Expansion Phases: Cycle 1 Day 1 and Cycle 1 Day 8 (each cycle is 21 days): predose and at multiple timepoints (up to 24 hours).
  description: AUCinf is defined as the Area Under the Concentration-time Curve from Time 0 to Infinity for ONM-501
  measure: Dose Escalation and Expansion Phases: CL/F
  time frame: Dose Escalation and Expansion Phases: Cycle 1 Day 1 and Cycle 1 Day 8 (each cycle is 21 days): predose and at multiple timepoints (up to 24 hours).
  description: CL/F is defined as the apparent clearance of ONM-501 (CL/F), where F is the fraction of the dose absorbed.
  measure: Dose Escalation and Expansion Phases: Vz/F
  time frame: Dose Escalation and Expansion Phases: Cycle 1 Day 1 and Cycle 1 Day 8 (each cycle is 21 days): predose and at multiple timepoints (up to 24 hours).
  description: Vz/F is defined as the apparent volume of distribution of ONM-501 (CL/F), where F is the fraction of the dose absorbed.
  measure: Expansion Phase Only: Objective Response Rate (ORR)
  time frame: Up to approximately 24 months
  description: Objective response will be defined as a best response of CR or PR. The objective response rate (ORR) will be calculated as the proportion of patients in the Efficacy Analysis Set who achieve an objective response. ORR will be assessed based on Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1.
  Characterize the plasma pharmacokinetics (PK) of IT ONM-501 as monotherapy and in combination with cemiplimab
  Evaluate additional measures of clinical benefit including: Duration of Response (DOR), Progression Free Survival (PFS) by RECIST and Overall Survival
  measure: Expansion Phase Only: Duration of Response (DOR)
  time frame: Up to approximately 24 months
  description: DOR analyses will be conducted for those patients in the Efficacy Analysis Set who achieve an objective response and is defined as the time from first objective status assessment of CR or PR until documentation of objective disease progression or death from any cause. Patients who do not progress and do not die will be censored on the date of last adequate tumor assessment. If no further adequate post-treatment tumor assessments were obtained for a patient, DOR will be censored at the date of the objective response (i.e., zero duration). DOR will be assessed based on RECIST v1.1.
  measure: Expansion Phase Only: Progression-Free Survival (PFS)
  time frame: Up to approximately 24 months
  description: PFS is defined as the time from administration of the first dose of ONM-501 until documentation of objective disease progression or death from any cause. Patients who do not progress and do not die will be censored on the date of last adequate tumor assessment. If no adequate post treatment tumor assessments were obtained for a patient, PFS will be censored at Day 1 (i.e., zero duration). The PFS analysis will be conducted using the Safety Analysis Set.
  Assess the biological effects of IT ONM-501 demonstrated by changes in immune cells, immune cell markers, serum cytokines (such as TNF-⍺, IFN-⍺, IFN-β, and others consistent with activation of the cGAS-STING pathway) and gene expression patterns
  measure: Expansion Phase Only: Overall Survival (OS)
  time frame: Up to approximately 24 months
  description: OS is defined as the time from the date of first dose administration to the date of death.
  arm group label: Part 1a: Monotherapy Dose Escalation
  arm group type: Experimental
  description: ONM-501 will be administered as intratumoral injections once per week for three weeks, followed by three weeks without ONM-501 administration. Each dosing cycle will be 21 days.
  arm group label: Part 1b: ONM-501 in Combination with cemiplimab
  arm group type: Experimental
  description: ONM-501 will be administered as intratumoral injections once per week for three weeks followed by three weeks without ONM-501 administration. Each dosing cycle will be 21 days. The combination agent will be administered according to standard protocol, once every three weeks.
  arm group label: Part 2: RDE ONM-501 in Combination with cemiplimab in indication-specific expansion cohorts
  arm group type: Experimental
  description: Once the recommended doses for expansion (RDEs) are determined for ONM-501 + ICI combination or ONM-501 monotherapy, the expansion phase of the study will be initiated. The expansion phase will enroll patients in one to three indication-specific expansion cohorts.
  intervention type: Drug
  intervention name: ONM-501
  description: Intratumoral injection
  arm group label: Part 1a: Monotherapy Dose Escalation
  arm group label: Part 1b: ONM-501 in Combination with cemiplimab
  arm group label: Part 2: RDE ONM-501 in Combination with cemiplimab in indication-specific expansion cohorts
  intervention type: Drug
  intervention name: Cemiplimab
  description: Intravenous administration of 350 mg
  arm group label: Part 1b: ONM-501 in Combination with cemiplimab
  arm group label: Part 2: RDE ONM-501 in Combination with cemiplimab in indication-specific expansion cohorts
  other name: Libtayo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Trials@OncoNanoMed.com
  phone: (682) 285-1411
  email: trials@onconanomed.com
  responsible party type: Sponsor
  mesh term: Lymphoma
  mesh term: Carcinoma
  mesh term: Neoplasms
  mesh term: Melanoma
  mesh term: Urinary Bladder Neoplasms
  mesh term: Lymphoma, Mantle-Cell
  mesh term: Lymphoma, Large B-Cell, Diffuse
  mesh term: Triple Negative Breast Neoplasms
  mesh term: Squamous Cell Carcinoma of Head and Neck
  mesh term: Skin Neoplasms
  mesh term: Carcinoma in Situ
  mesh term: Lymphoma, Non-Hodgkin
  mesh term: Uterine Cervical Neoplasms
  mesh term: Recurrence
  mesh term: Cemiplimab