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/NCT06034860</url>
    </required_header>
    <id_info>
      <org_study_id>MT-8421-001</org_study_id>
      <nct_id>NCT06034860</nct_id>
    </id_info>
    <brief_title>Study of MT-8421 as Monotherapy and in Combination With Nivolumab in Patients With Selected Advanced Solid Cancer Types</brief_title>
    <official_title>A Phase 1 Open-label, Multicenter, Dose-ranging Study to Investigate Safety and Tolerability, Efficacy, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of MT-8421 as Monotherapy and in Combination With Nivolumab in Patients With Selected Advanced Solid Cancer Types</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Molecular Templates, Inc.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Molecular Templates, 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>
        This is a Phase 1, open-label, dose escalation and expansion study of MT-8421 (an Engineered&#xD;
        Toxin Body (ETB)) as monotherapy and in combination with nivolumab in patients with selected&#xD;
        advanced solid cancer types. MT-8421 is an investigational drug that specifically targets and&#xD;
        depletes cytotoxic T-lymphocytes-associated protein 4 (CTLA-4) expressing cells in an effort&#xD;
        to directly dismantle the tumor microenvironment for the treatment of patients with advanced&#xD;
        solid tumors.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This study is conducted in two parts. The study will enroll up to 200 total participants (up&#xD;
        to 40 in Part A and up to 160 in Part B).&#xD;
  &#xD;
        Part A (Dose Escalation) is designed to estimate the maximum tolerated dose (MTD) of MT-8421&#xD;
        as monotherapy and in combination with nivolumab.&#xD;
  &#xD;
        Part B (Dose Expansion) is designed to identify the dose(s) to be studied in Phase 2.&#xD;
  &#xD;
        The drug being tested in this study is called MT-8421. The study will evaluate safety,&#xD;
        tolerability, efficacy, pharmacokinetics, pharmacodynamics, and immunogenicity of MT-8421 as&#xD;
        monotherapy and in combination with nivolumab in patients with selected advanced solid cancer&#xD;
        types.&#xD;
  &#xD;
        MT-8421 will be given as an intravenous (IV) infusion on Days 1, 8, 15, and 22 of a 28-day&#xD;
        cycle. H1 and H2 blockers and anti-pyretics will be given to all patients as pre-medication&#xD;
        prior to each dose in Cycle 1. Anti-pyretics will be required for 24 hours after the first&#xD;
        dose in Cycle 1. Use of pre-medication will be at the discretion of the Investigator for&#xD;
        subsequent doses.&#xD;
  &#xD;
        In Parts A and B, a subject may participate for the following three (3) periods:&#xD;
  &#xD;
          -  Screening Period- up to 28 days before the first dose of MT-8421&#xD;
  &#xD;
          -  Treatment Period- active period where a subject will receive doses of MT-8421 over a&#xD;
             28-day treatment period.&#xD;
  &#xD;
          -  Follow-up Period- up to 24 months after the second short term follow up visit.&#xD;
  &#xD;
        In both parts of the study, participants can receive MT-8421 until their cancer worsens, side&#xD;
        effects prevent further study treatment, or until the participant leaves the study for other&#xD;
        reasons decided by the participant, the study doctor, or the sponsor of the study. After the&#xD;
        second short term follow up visit participants will have a check -up of their disease every&#xD;
        12 weeks for 24 months.&#xD;
  &#xD;
        The overall duration of the study will vary for each participant because study treatment will&#xD;
        continue until unacceptable toxicity, withdrawal of consent, death, termination of the study&#xD;
        by the sponsor, or fulfilment of another discontinuation criterion.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">October 2026</completion_date>
    <primary_completion_date type="Anticipated">July 2026</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Number of participants with Adverse Events</measure>
      <time_frame>28 day cycle</time_frame>
      <description>Evaluation of safety and tolerability of MT-8421 as measured by number of participants with Adverse Events, dose limiting toxicities (DLTs), abnormal physical exam findings, abnormal laboratory test results, abnormal radiographic findings, and/or patient reported symptoms</description>
    </primary_outcome>
    <primary_outcome>
      <measure>To confirm the recommended Phase 2 dose (RP2D) of MT-8421 as monotherapy and in combination with nivolumab in patients with selected advanced solid tumor types.</measure>
      <time_frame>28 day cycle</time_frame>
      <description>Incidence of AEs</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Proportion of participants with objective response</measure>
      <time_frame>Up to two years (Part B)</time_frame>
      <description>Objective response rate (ORR) defined as the proportion of participants with either a complete response or a partial response as determined by investigator assessment using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Objective response rate to assess preliminary efficacy</measure>
      <time_frame>Up to two years (Parts A)</time_frame>
      <description>Objective response rate (ORR) defined as the proportion of participants with either a complete response or a partial response as determined by investigator assessment using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of response to assess preliminary efficacy</measure>
      <time_frame>Up to two years (Parts A)</time_frame>
      <description>Duration of response defined for participants with confirmed complete response or partial response as the time from the first documented tumor response to the date of radiographic progression progressive disease per RECIST v1.1</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to response to assess preliminary efficacy</measure>
      <time_frame>Up to two years (Parts A)</time_frame>
      <description>Time to response defined as the time from the date of the first dose of the study treatment to the date of the first documentation of response (partial response or better) per RECIST v1.1</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression-free survival to assess preliminary efficacy</measure>
      <time_frame>Up to two years (Parts A)</time_frame>
      <description>Progression free survival defined as the time from the start of treatment with MT-8421 to the date of radiographic progressive disease per RECIST v1.1 or death from any cause, not including clinical progression</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease control rate to assess preliminary efficacy</measure>
      <time_frame>Up to two years (Parts A)</time_frame>
      <description>Disease control rate defined as proportion of patients who have achieved complete response, partial response and stable disease</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Characterize the pharmacokinetic (PK) profile of MT-8421 given as monotherapy and in combination with nivolumab in patients with selected advanced solid tumor types</measure>
      <time_frame>Up to two years (Parts A)</time_frame>
      <description>Maximum observed plasma concentration (Cmax)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Characterize the pharmacokinetic (PK) profile of MT-8421 given as monotherapy and in combination with nivolumab in patients with selected advanced solid tumor types</measure>
      <time_frame>Up to two years (Parts A and B)</time_frame>
      <description>Half-life (t1/2)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Characterize the pharmacokinetic (PK) profile of MT-8421 given as monotherapy and in combination with nivolumab in patients with selected advanced solid tumor types</measure>
      <time_frame>Up to two years (Parts A and B)</time_frame>
      <description>Area under the concentration-time curve (AUC) from time zero to the last measurable concentration (AUC0-t), total exposure (AUC0-∞)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Characterize the pharmacokinetic (PK) profile of MT-8421 given as monotherapy and in combination with nivolumab in patients with selected advanced solid tumor types</measure>
      <time_frame>Up to two years (Parts A and B)</time_frame>
      <description>Clearance (CL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Characterize the pharmacokinetic (PK) profile of MT-8421 given as monotherapy and in combination with nivolumab in patients with selected advanced solid tumor types</measure>
      <time_frame>Up to two years (Parts A and B)</time_frame>
      <description>Volume of distribution at steady-state (Vss)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Evaluate the immunogenicity of MT-8421 in patients with selected advanced solid tumors.</measure>
      <time_frame>Up to two years (Parts A and B)</time_frame>
      <description>Anti-drug antibodies (ADA), Neutralizing antibodies (NAb)</description>
    </secondary_outcome>
    <number_of_arms>4</number_of_arms>
    <enrollment type="Anticipated">200</enrollment>
    <condition>Non Small Cell Lung Cancer</condition>
    <condition>Hepatocellular Carcinoma</condition>
    <condition>Melanoma</condition>
    <condition>Renal Cell Carcinoma</condition>
    <condition>Microsatellite Instability High</condition>
    <condition>Mismatch Repair Deficiency</condition>
    <condition>Mesothelioma</condition>
    <condition>Esophageal Squamous Cell Carcinoma</condition>
    <condition>Squamous Cell Carcinoma of Head and Neck</condition>
    <condition>Urothelial Carcinoma</condition>
    <condition>Cervical Cancer</condition>
    <arm_group>
      <arm_group_label>Part A- Dose Escalation Monotherapy</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Part A- Dose escalation of MT-8421 monotherapy in patients with selected advanced solid tumors.&#xD;
  The assigned dose level of MT-8421 will be given as an intravenous (IV) infusion over about 30 minutes on the same day every week (i.e. on day 1, day 8, day 15, and day 22 of each 28-day cycle).</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Part A- Dose Escalation Combination Therapy</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Part A- Dose escalation of MT-8421 in combination with nivolumab in patients with selected advanced solid tumors.&#xD;
  The assigned dose level of MT-8421 will be given as an intravenous (IV) infusion over about 30 minutes prior to the infusion of 480 mg nivolumab. MT-8421 will be given on the same day every week (i.e. on day 1, day 8, day 15, and day 22 of each 28-day cycle). Nivolumab will be given on the first day of each cycle beginning at cycle 2.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Part B Dose Expansion Monotherapy</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Part B- Dose expansion of MT-8421 monotherapy in patients with selected advanced solid tumors.&#xD;
  Part B monotherapy will include two expansion groups: Group B1 (NSCLC) and group B2 (HCC).&#xD;
  The assigned dose level of MT-8421 determined in Part A will be given as an intravenous (IV) infusion over about 30 minutes on the same day every week (i.e. on day 1, day 8, day 15, and day 22 of each 28-day cycle).</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Part B Dose Expansion Combination</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Part B- Dose escalation of MT-8421 in combination with nivolumab in patients with selected advanced solid tumors.&#xD;
  Part B combination therapy will include two expansion groups: Group B3 (Melanoma) and Group B4 (RCC).&#xD;
  The assigned dose level of MT-8421 determined in Part A will be given as an intravenous (IV) infusion over about 30 minutes prior to the infusion of 480 mg nivolumab. MT-8421 will be given on the same day every week (i.e. on day 1, day 8, day 15, and day 22 of each 28-day cycle). Nivolumab will be given on the first day of each cycle beginning at cycle 2.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>MT-8421</intervention_name>
      <description>Experimental treatment with MT-8421</description>
      <arm_group_label>Part A- Dose Escalation Combination Therapy</arm_group_label>
      <arm_group_label>Part A- Dose Escalation Monotherapy</arm_group_label>
      <arm_group_label>Part B Dose Expansion Combination</arm_group_label>
      <arm_group_label>Part B Dose Expansion Monotherapy</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Nivolumab</intervention_name>
      <description>480 mg nivolumab administered on Day 1 of each cycle starting with Cycle 2 for all combination dose escalation and dose expansion cohorts</description>
      <arm_group_label>Part A- Dose Escalation Combination Therapy</arm_group_label>
      <arm_group_label>Part B Dose Expansion Combination</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Histologically confirmed, unresectable, locally advanced, or metastatic melanoma, HCC,&#xD;
               NSCLC, RCC, MSI-H/dMMR malignancies, urothelial carcinoma, esophageal squamous cell&#xD;
               carcinoma, mesothelioma, SCCHN, or cervical carcinoma not amenable to standard&#xD;
               treatment, or standard treatment is not available, or in the Investigator's opinion,&#xD;
               the standard treatment would not be in the patient's best interest.&#xD;
  &#xD;
          Part A only: Evaluable only or measurable disease according to RECIST v1.1 Part B only: At&#xD;
          least 1 measurable tumor lesion according to RECIST v1.1&#xD;
  &#xD;
            -  Prior treatment must include a PD-1 or programmed cell death - ligand 1 (PD-L1)&#xD;
               inhibitor. Prior treatment with a CTLA-4 inhibitor is not required.&#xD;
  &#xD;
            -  Eastern Cooperate Oncology Group (ECOG) performance score of 0 or 1&#xD;
  &#xD;
            -  Adequate bone marrow function, as determined by:&#xD;
  &#xD;
                 -  Absolute neutrophil count (ANC) ≥ 1500/ μL (should not have received growth&#xD;
                    factors within 2 weeks prior to screening)&#xD;
  &#xD;
                 -  Platelet count ≥ 75,000/ μL&#xD;
  &#xD;
                 -  Hemoglobin ≥ 8.0 g/dL (no red blood cell transfusion within 2 weeks of study&#xD;
                    treatment start is allowed)&#xD;
  &#xD;
            -  Adequate renal function, based on estimated creatinine clearance (eCrCl) ≥ 50 mL/min,&#xD;
               calculated by the Cockcroft-Gault equation.&#xD;
  &#xD;
            -  Adequate hepatic function, as determined by:&#xD;
  &#xD;
                 -  Total bilirubin ≤ 1.5x upper limit of normal (ULN) or ≤ 2x ULN direct bilirubin&#xD;
                    for patients with Gilbert's Syndrome&#xD;
  &#xD;
                 -  Aspartate transaminase (AST) ≤ 3x ULN (or ≤ 5x ULN if liver metastasis or HCC).&#xD;
  &#xD;
                 -  Alanine transaminase (ALT) ≤ 3x ULN (or ≤ 5x ULN if liver metastasis or HCC).&#xD;
  &#xD;
                 -  Adequate serum albumin (albumin ≥ 2.5 g/dL)&#xD;
  &#xD;
            -  Availability of a lesion that can be biopsied with acceptable risk.&#xD;
  &#xD;
            -  Patients capable of bearing children must have a negative highly sensitive pregnancy&#xD;
               test within 72 hours before the start of treatment. Patients who are postmenopausal (&gt;&#xD;
               1 year since last menstrual cycle) or permanently sterilized (e.g., bilateral tubal&#xD;
               occlusion, hysterectomy, bilateral salpingectomy) may be considered as not of&#xD;
               reproductive potential.&#xD;
  &#xD;
            -  Patients of reproductive potential must agree either to abstain continuously from&#xD;
               heterosexual intercourse or to use a highly effective birth control method from&#xD;
               signing the informed consent form (ICF) until 30 days after the last dose of MT-8421&#xD;
               and/or 5 months after the last dose of nivolumab for patients capable of bearing&#xD;
               children and until 90 days after the last dose of MT-8421 for patients capable of&#xD;
               fathering a child. Patients must not donate sperm during the study and for 90 days&#xD;
               after the last dose of nivolumab or MT-8421.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Unwilling or unable to undergo 2 sets of 3 to 6 core tumor biopsies: one set at study&#xD;
               baseline (prior to first dose of study drug) and one set between Weeks 6 through 8. A&#xD;
               final optional set will be collected time of disease progression.&#xD;
  &#xD;
            -  Received approved or investigational treatment for the disease under study (except&#xD;
               ipilimumab) where Exclusion Criterion 4 applies, requiring a washout that will be&#xD;
               dependent upon prior ipilimumab dose and planned MT-8421 dose) within 4 weeks before&#xD;
               the start of treatment. For small molecules [Molecular Weight (MW) &lt; 0.9 kDa], the&#xD;
               washout is 5 half-lives, but at least 2 weeks.&#xD;
  &#xD;
            -  Received tremelimumab within 30 days or ipilimumab 3 mg/kg within 60 days or&#xD;
               ipilimumab 1 mg/kg within 30 days before the start of treatment. Once dose cohort of&#xD;
               32 µg/kg MT-8421 has been completed in dose escalation, a 30-day washout of ipilimumab&#xD;
               is acceptable irrespective of prior dose.&#xD;
  &#xD;
            -  Any concurrent cancer treatment, apart from local treatment of non-target lesions for&#xD;
               palliative intent (e.g., local surgery or radiotherapy). Patient must have recovered&#xD;
               from the effects of the local treatment and be discussed with the medical monitor.&#xD;
  &#xD;
            -  History or current evidence of another neoplastic disease, except cervical carcinoma&#xD;
               in situ; superficial non-invasive bladder tumors, curatively treated; Stage I to II&#xD;
               non-melanoma skin cancer; prostate cancer managed by active surveillance; or any&#xD;
               previous cancer curatively treated &lt; 2 years before the start of treatment.&#xD;
  &#xD;
            -  Active autoimmune disease that required systemic treatment in the past. Patients who&#xD;
               have not required systemic treatment for at least 2 years may be enrolled if&#xD;
               permission is provided after discussion with the Medical Monitor (replacement therapy,&#xD;
               e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for&#xD;
               adrenal or pituitary insufficiency is allowed)&#xD;
  &#xD;
            -  Evidence of active, non-infectious ≥ Grade 2 pneumonitis or current evidence of ≥&#xD;
               Grade 3 other underlying pulmonary disease.&#xD;
  &#xD;
            -  Ongoing &gt; Grade 1 immune-related toxicity caused by prior CPI therapy (i.e., PD-1&#xD;
               inhibitors, PDL1 inhibitors, or CTLA-4 inhibitors). Patients with stable&#xD;
               endocrinological AEs (e.g., hypothyroidism, adrenal insufficiency, hypopituitarism, or&#xD;
               diabetes mellitus) must have been on a stable dose of supplemental therapy for at&#xD;
               least 2 weeks before screening to be eligible for this study. History of repeat Grade&#xD;
               2 pneumonitis or myocarditis on previous CPI and/or Grade 3 irAE on previous CPI&#xD;
               treatment.&#xD;
  &#xD;
            -  Current evidence of new or growing central nervous system (CNS) metastases during&#xD;
               screening. Patients with known CNS metastases will be eligible if they meet all the&#xD;
               following criteria:&#xD;
  &#xD;
                 -  Received radiotherapy or another appropriate therapy for the CNS metastases, if&#xD;
                    clinically Indicated&#xD;
  &#xD;
                 -  Have stable CNS disease on the computed tomography (CT) or magnetic resonance&#xD;
                    imaging (MRI) scan within 4 weeks before signing the ICF compared with prior&#xD;
                    neuroimaging.&#xD;
  &#xD;
            -  History or current evidence of significant cardiovascular disease before the start of&#xD;
               treatment.&#xD;
  &#xD;
            -  Current evidence of active, uncontrolled hepatitis B virus, hepatitis C virus, human&#xD;
               immunodeficiency virus (HIV) (evidenced by detectable viral load by polymerase chain&#xD;
               reaction) or acquired immunodeficiency syndrome (AIDS)-related illness.&#xD;
  &#xD;
                 -  Serology and virology measurements are not required to be performed at screening,&#xD;
                    but any previously reported results should be used for eligibility purposes.&#xD;
                    Investigators will test per their discretion&#xD;
  &#xD;
                 -  Patients with a history of treated hepatitis C and non-quantifiable hepatitis C&#xD;
                    virus- ribonucleic acid (RNA) may be enrolled.&#xD;
  &#xD;
                 -  Patients on treatment for hepatitis B, hepatitis C, and/or HIV will be eligible&#xD;
                    if they have undetectable viral load (patients with HIV with CD4+ T-cell [CD4+]&#xD;
                    counts ≥ 350 cells/µL may be enrolled).&#xD;
  &#xD;
            -  Patients with unintentional weight loss greater than 10% of their body weight over the&#xD;
               preceding 2 months or less prior to first dose in the first cycle.&#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>Admasu Mamuye, MD</last_name>
      <role>Study Director</role>
      <affiliation>Molecular Templates</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Jennifer Wilcox</last_name>
      <phone>512-368-9807</phone>
      <email>jennifer.wilcox@mtem.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>The Angeles Clinic</name>
        <address>
          <city>Los Angeles</city>
          <state>California</state>
          <zip>90025</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Saba Mukarram</last_name>
        <phone>310-231-2181</phone>
        <email>smukarram@theangelesclinic.org</email>
      </contact>
      <investigator>
        <last_name>Justin Moyers, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Horizon Oncology Research, LLC</name>
        <address>
          <city>Lafayette</city>
          <state>Indiana</state>
          <zip>47905</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Costantine Albany, MD</last_name>
        <phone>765-446-5114</phone>
        <email>calbany@horizonbioadvance.com</email>
      </contact>
      <investigator>
        <last_name>Costantine Albany, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Washington University in St. Louis</name>
        <address>
          <city>Saint Louis</city>
          <state>Missouri</state>
          <zip>63110</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Cindy Fogal, PhD</last_name>
        <phone>314-362-1518</phone>
        <email>clfogal@wustl.edu</email>
      </contact>
      <investigator>
        <last_name>Brian VanTine, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Weill Cornell Medicine</name>
        <address>
          <city>New York</city>
          <state>New York</state>
          <zip>10065</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Mahelia Bissassar</last_name>
        <phone>646-962-7669</phone>
        <email>mab4028@med.cornell.edu</email>
      </contact>
      <investigator>
        <last_name>Anna Pavlick, DO</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>NEXT Oncology</name>
        <address>
          <city>Fairfax</city>
          <state>Virginia</state>
          <zip>22031</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Blake Patterson</last_name>
        <phone>703-783-4505</phone>
        <email>mpoole@nextoncology.com</email>
      </contact>
      <investigator>
        <last_name>Alexander Spira, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 23, 2023</study_first_submitted>
    <study_first_submitted_qc>September 5, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 13, 2023</study_first_posted>
    <last_update_submitted>September 5, 2023</last_update_submitted>
    <last_update_submitted_qc>September 5, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 13, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Carcinoma</mesh_term>
      <mesh_term>Carcinoma, Squamous Cell</mesh_term>
      <mesh_term>Carcinoma, Renal Cell</mesh_term>
      <mesh_term>Mesothelioma</mesh_term>
      <mesh_term>Esophageal Squamous Cell Carcinoma</mesh_term>
      <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
      <mesh_term>Microsatellite Instability</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Nivolumab</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- 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/NCT06034860
  org study id: MT-8421-001
  nct id: NCT06034860
  lead sponsor: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: No
  This is a Phase 1, open-label, dose escalation and expansion study of MT-8421 (an Engineered
        Toxin Body (ETB)) as monotherapy and in combination with nivolumab in patients with selected
        advanced solid cancer types. MT-8421 is an investigational drug that specifically targets and
        depletes cytotoxic T-lymphocytes-associated protein 4 (CTLA-4) expressing cells in an effort
        to directly dismantle the tumor microenvironment for the treatment of patients with advanced
        solid tumors.
  This study is conducted in two parts. The study will enroll up to 200 total participants (up
        to 40 in Part A and up to 160 in Part B).
  
        Part A (Dose Escalation) is designed to estimate the maximum tolerated dose (MTD) of MT-8421
        as monotherapy and in combination with nivolumab.
  
        Part B (Dose Expansion) is designed to identify the dose(s) to be studied in Phase 2.
  
        The drug being tested in this study is called MT-8421. The study will evaluate safety,
        tolerability, efficacy, pharmacokinetics, pharmacodynamics, and immunogenicity of MT-8421 as
        monotherapy and in combination with nivolumab in patients with selected advanced solid cancer
        types.
  
        MT-8421 will be given as an intravenous (IV) infusion on Days 1, 8, 15, and 22 of a 28-day
        cycle. H1 and H2 blockers and anti-pyretics will be given to all patients as pre-medication
        prior to each dose in Cycle 1. Anti-pyretics will be required for 24 hours after the first
        dose in Cycle 1. Use of pre-medication will be at the discretion of the Investigator for
        subsequent doses.
  
        In Parts A and B, a subject may participate for the following three (3) periods:
  
          -  Screening Period- up to 28 days before the first dose of MT-8421
  
          -  Treatment Period- active period where a subject will receive doses of MT-8421 over a
             28-day treatment period.
  
          -  Follow-up Period- up to 24 months after the second short term follow up visit.
  
        In both parts of the study, participants can receive MT-8421 until their cancer worsens, side
        effects prevent further study treatment, or until the participant leaves the study for other
        reasons decided by the participant, the study doctor, or the sponsor of the study. After the
        second short term follow up visit participants will have a check -up of their disease every
        12 weeks for 24 months.
  
        The overall duration of the study will vary for each participant because study treatment will
        continue until unacceptable toxicity, withdrawal of consent, death, termination of the study
        by the sponsor, or fulfilment of another discontinuation criterion.
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Number of participants with Adverse Events
  time frame: 28 day cycle
  description: Evaluation of safety and tolerability of MT-8421 as measured by number of participants with Adverse Events, dose limiting toxicities (DLTs), abnormal physical exam findings, abnormal laboratory test results, abnormal radiographic findings, and/or patient reported symptoms
  measure: To confirm the recommended Phase 2 dose (RP2D) of MT-8421 as monotherapy and in combination with nivolumab in patients with selected advanced solid tumor types.
  time frame: 28 day cycle
  description: Incidence of AEs
  measure: Proportion of participants with objective response
  time frame: Up to two years (Part B)
  description: Objective response rate (ORR) defined as the proportion of participants with either a complete response or a partial response as determined by investigator assessment using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
  measure: Objective response rate to assess preliminary efficacy
  time frame: Up to two years (Parts A)
  description: Objective response rate (ORR) defined as the proportion of participants with either a complete response or a partial response as determined by investigator assessment using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
  measure: Duration of response to assess preliminary efficacy
  time frame: Up to two years (Parts A)
  description: Duration of response defined for participants with confirmed complete response or partial response as the time from the first documented tumor response to the date of radiographic progression progressive disease per RECIST v1.1
  measure: Time to response to assess preliminary efficacy
  time frame: Up to two years (Parts A)
  description: Time to response defined as the time from the date of the first dose of the study treatment to the date of the first documentation of response (partial response or better) per RECIST v1.1
  measure: Progression-free survival to assess preliminary efficacy
  time frame: Up to two years (Parts A)
  description: Progression free survival defined as the time from the start of treatment with MT-8421 to the date of radiographic progressive disease per RECIST v1.1 or death from any cause, not including clinical progression
  measure: Disease control rate to assess preliminary efficacy
  time frame: Up to two years (Parts A)
  description: Disease control rate defined as proportion of patients who have achieved complete response, partial response and stable disease
  measure: Characterize the pharmacokinetic (PK) profile of MT-8421 given as monotherapy and in combination with nivolumab in patients with selected advanced solid tumor types
  time frame: Up to two years (Parts A)
  description: Maximum observed plasma concentration (Cmax)
  measure: Characterize the pharmacokinetic (PK) profile of MT-8421 given as monotherapy and in combination with nivolumab in patients with selected advanced solid tumor types
  time frame: Up to two years (Parts A and B)
  description: Half-life (t1/2)
  measure: Characterize the pharmacokinetic (PK) profile of MT-8421 given as monotherapy and in combination with nivolumab in patients with selected advanced solid tumor types
  time frame: Up to two years (Parts A and B)
  description: Area under the concentration-time curve (AUC) from time zero to the last measurable concentration (AUC0-t), total exposure (AUC0-∞)
  measure: Characterize the pharmacokinetic (PK) profile of MT-8421 given as monotherapy and in combination with nivolumab in patients with selected advanced solid tumor types
  time frame: Up to two years (Parts A and B)
  description: Clearance (CL)
  measure: Characterize the pharmacokinetic (PK) profile of MT-8421 given as monotherapy and in combination with nivolumab in patients with selected advanced solid tumor types
  time frame: Up to two years (Parts A and B)
  description: Volume of distribution at steady-state (Vss)
  measure: Evaluate the immunogenicity of MT-8421 in patients with selected advanced solid tumors.
  time frame: Up to two years (Parts A and B)
  description: Anti-drug antibodies (ADA), Neutralizing antibodies (NAb)
  arm group label: Part A- Dose Escalation Monotherapy
  arm group type: Experimental
  description: Part A- Dose escalation of MT-8421 monotherapy in patients with selected advanced solid tumors.
  The assigned dose level of MT-8421 will be given as an intravenous (IV) infusion over about 30 minutes on the same day every week (i.e. on day 1, day 8, day 15, and day 22 of each 28-day cycle).
  arm group label: Part A- Dose Escalation Combination Therapy
  arm group type: Experimental
  description: Part A- Dose escalation of MT-8421 in combination with nivolumab in patients with selected advanced solid tumors.
  The assigned dose level of MT-8421 will be given as an intravenous (IV) infusion over about 30 minutes prior to the infusion of 480 mg nivolumab. MT-8421 will be given on the same day every week (i.e. on day 1, day 8, day 15, and day 22 of each 28-day cycle). Nivolumab will be given on the first day of each cycle beginning at cycle 2.
  arm group label: Part B Dose Expansion Monotherapy
  arm group type: Experimental
  description: Part B- Dose expansion of MT-8421 monotherapy in patients with selected advanced solid tumors.
  Part B monotherapy will include two expansion groups: Group B1 (NSCLC) and group B2 (HCC).
  The assigned dose level of MT-8421 determined in Part A will be given as an intravenous (IV) infusion over about 30 minutes on the same day every week (i.e. on day 1, day 8, day 15, and day 22 of each 28-day cycle).
  arm group label: Part B Dose Expansion Combination
  arm group type: Experimental
  description: Part B- Dose escalation of MT-8421 in combination with nivolumab in patients with selected advanced solid tumors.
  Part B combination therapy will include two expansion groups: Group B3 (Melanoma) and Group B4 (RCC).
  The assigned dose level of MT-8421 determined in Part A will be given as an intravenous (IV) infusion over about 30 minutes prior to the infusion of 480 mg nivolumab. MT-8421 will be given on the same day every week (i.e. on day 1, day 8, day 15, and day 22 of each 28-day cycle). Nivolumab will be given on the first day of each cycle beginning at cycle 2.
  intervention type: Drug
  intervention name: MT-8421
  description: Experimental treatment with MT-8421
  arm group label: Part A- Dose Escalation Combination Therapy
  arm group label: Part A- Dose Escalation Monotherapy
  arm group label: Part B Dose Expansion Combination
  arm group label: Part B Dose Expansion Monotherapy
  intervention type: Drug
  intervention name: Nivolumab
  description: 480 mg nivolumab administered on Day 1 of each cycle starting with Cycle 2 for all combination dose escalation and dose expansion cohorts
  arm group label: Part A- Dose Escalation Combination Therapy
  arm group label: Part B Dose Expansion Combination
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Admasu Mamuye, MD
  role: Study Director
  affiliation: Molecular Templates
  last name: Jennifer Wilcox
  phone: 512-368-9807
  email: jennifer.wilcox@mtem.com
  facility: 
  status: Recruiting
  contact: 
  investigator: 
  facility: 
  status: Recruiting
  contact: 
  investigator: 
  facility: 
  status: Recruiting
  contact: 
  investigator: 
  facility: 
  status: Not yet recruiting
  contact: 
  investigator: 
  facility: 
  status: Recruiting
  contact: 
  investigator: 
  country: United States
  responsible party type: Sponsor
  mesh term: Carcinoma
  mesh term: Carcinoma, Squamous Cell
  mesh term: Carcinoma, Renal Cell
  mesh term: Mesothelioma
  mesh term: Esophageal Squamous Cell Carcinoma
  mesh term: Squamous Cell Carcinoma of Head and Neck
  mesh term: Microsatellite Instability
  mesh term: Nivolumab
  sharing ipd: No