<clinical_study>
  <!-- This xml conforms to an XML Schema at:
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  <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/NCT04420884</url>
  </required_header>
  <id_info>
    <org_study_id>TAK-676-1002</org_study_id>
    <secondary_id>U1111-1241-4427</secondary_id>
    <secondary_id>2022-000528-39</secondary_id>
    <nct_id>NCT04420884</nct_id>
  </id_info>
  <brief_title>A Study of TAK-676 as Single Agent and TAK-676 in Combination With Pembrolizumab in Adults With Advanced or Metastatic Solid Tumors</brief_title>
  <official_title>An Open-label, Dose Escalation, Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of TAK-676 as a Single Agent and in Combination With Pembrolizumab in Adult Patients With Advanced or Metastatic Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Takeda</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Takeda</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 main aim of this study is to check if people with advanced solid tumors have side effects&#xD;
      from TAK-676, and to check how much TAK-676 they can receive without getting significant side&#xD;
      effects from it when given alone and in combination with pembrolizumab. The study will be&#xD;
      conducted in two phases including a dose escalation phase and a dose expansion phase. In the&#xD;
      dose escalation phase, escalating doses of TAK-676 are being tested alone and in combination&#xD;
      with pembrolizumab to treat participants who have advanced or metastatic solid tumors. In the&#xD;
      dose expansion phase, TAK-676 will be studied with pembrolizumab with or without chemotherapy&#xD;
      in participants with untreated metastatic or recurrent, unresectable squamous cell carcinoma&#xD;
      of head and neck (SCCHN) and in combination with pembrolizumab in third-line or later&#xD;
      recurrent locally advanced or metastatic microsatellite instability-high /mismatch repair&#xD;
      deficient (MSI-H/dMMR) and third-line recurrent locally advanced or metastatic microsatellite&#xD;
      stable/mismatch repair proficient (MSS/pMMR) colorectal cancer (CRC).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The drug being tested in this study is called TAK-676. TAK-676 is being tested to treat&#xD;
      people who have advanced or metastatic solid tumors.&#xD;
&#xD;
      The study will enroll approximately 288 participants. Part 1 consists of an initial Safety&#xD;
      Lead-in to Dose Escalation Phase; Part 2 and Part 3 compose the Expansion Phase in 2 specific&#xD;
      indications namely, previously untreated metastatic or recurrent, unresectable SCCHN (Part 2)&#xD;
      and third-line or later recurrent locally advanced or metastatic MSI-H/dMMR and third-line&#xD;
      recurrent locally advanced or metastatic MSS/pMMR CRC (Part 3). Participants will be assigned&#xD;
      to the following treatment groups in the respective Phases of the study:&#xD;
&#xD;
        -  Part 1 (Dose Escalation Phase): Safety Lead-in + TAK-676 SA [Part 1A] TAK-676 0.1&#xD;
           milligram (mg) in the Safety Lead-in followed by TAK-676 as escalating doses (0.2 mg and&#xD;
           above) in Part 1A.&#xD;
&#xD;
        -  Part 1B (Combination Dose Escalation Phase): TAK-676 as escalating doses (0.2 mg and&#xD;
           above) + Pembrolizumab&#xD;
&#xD;
      Once a safe and effective dose is recommended from Part 1, participants of select advanced or&#xD;
      metastatic solid tumors will receive TAK-676 in below defined cohorts in the expansion phase:&#xD;
&#xD;
        -  Part 2A (SCCHN Dose Expansion Phase): TAK-676 + Pembrolizumab&#xD;
&#xD;
        -  Part 2B (SCCHN Dose Expansion Phase): TAK-676 + Pembrolizumab + Chemotherapy&#xD;
&#xD;
        -  Part 3A (Expansion Phase in CRC): TAK-676 + Pembrolizumab in MSI-H/dMMR CRC&#xD;
&#xD;
        -  Part 3B (Expansion Phase in CRC): TAK-676 + Pembrolizumab in MSS/pMMR CRC&#xD;
&#xD;
      This multi-center trial will be conducted worldwide. The overall time to participate in this&#xD;
      study is 54 months. Participants will make multiple visits to the clinic, including 30 days&#xD;
      after last dose of study drug for a follow-up assessment. Patients in Parts 2 and 3 will be&#xD;
      followed for survival for up to 12 months after the last dose of study drug.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 22, 2020</start_date>
  <completion_date type="Anticipated">July 3, 2025</completion_date>
  <primary_completion_date type="Anticipated">July 3, 2025</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants Reporting one or More Treatment-emergent Adverse Events (TEAEs) and Based on TEAEs Severity</measure>
    <time_frame>Up to approximately 54 months</time_frame>
    <description>A severity grade is defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0. 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>Number of Participants with Dose-Limiting Toxicities (DLTs)</measure>
    <time_frame>Up to approximately 54 months</time_frame>
    <description>A DLT will be defined as any of the TEAEs, but not limited to, those that occur during Cycle 1 and are considered by the investigator to be at least possibly related to TAK-676 as a single agent (SA) or in combination with pembrolizumab. TEAEs meeting DLT definitions occurring in Cycle 2 or later will be considered in the determination of the recommended phase 2 dose (RP2D) of TAK-676, both in the TAK-676 SA and the combination with pembrolizumab arms. Toxicity will be evaluated according to NCI CTCAE version 5.0.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants Reporting One or More Treatment Emergent Serious Adverse Event (SAEs)</measure>
    <time_frame>Up to approximately 54 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With one or More TEAEs Leading to Dose Modifications and Treatment Discontinuations</measure>
    <time_frame>Up to approximately 54 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Dose Escalation and Expansion Phases: Cmax: Maximum Observed Plasma Concentration for TAK-676</measure>
    <time_frame>Dose Escalation and Expansion Phases: Cycle 1 Days 1, 8 and 15: pre-infusion and at multiple time points (up to 24 hours) post-infusion and at Day 1 for further cycles up to 54 months (Cycle length=21 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose Escalation and Expansion Phases: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-676</measure>
    <time_frame>Dose Escalation and Expansion Phases: Cycle 1 Days 1, 8 and 15: pre-infusion and at multiple time points (up to 24 hours) post-infusion and at Day 1 for further cycles up to 54 months (Cycle length=21 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose Escalation and Expansion Phases: AUCt: Area Under the Concentration-time Curve From Time 0 to Time t for TAK-676</measure>
    <time_frame>Dose Escalation and Expansion Phases: Cycle 1 Days 1, 8 and 15: pre-infusion and at multiple time points (up to 24 hours) post-infusion and at Day 1 for further cycles up to 54 months (Cycle length=21 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose Escalation and Expansion Phases: AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity for TAK-676</measure>
    <time_frame>Dose Escalation and Expansion Phases: Cycle 1 Days 1, 8 and 15: pre-infusion and at multiple time points (up to 24 hours) post-infusion and at Day 1 for further cycles up to 54 months (Cycle length=21 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose Escalation and Expansion Phases: t1/2z: Terminal Disposition Phase Half-life for TAK-676</measure>
    <time_frame>Dose Escalation and Expansion Phases: Cycle 1 Days 1, 8 and 15: pre-infusion and at multiple time points (up to 24 hours) post-infusion and at Day 1 for further cycles up to 54 months (Cycle length=21 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose Escalation and Expansion Phases: CL: Total Clearance After Intravenous Administration for TAK-676</measure>
    <time_frame>Dose Escalation and Expansion Phases: Cycle 1 Days 1, 8 and 15: pre-infusion and at multiple time points (up to 24 hours) post-infusion and at Day 1 for further cycles up to 54 months (Cycle length=21 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose Escalation and Expansion Phases: Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-676</measure>
    <time_frame>Dose Escalation and Expansion Phases: Cycle 1 Days 1, 8 and 15: pre-infusion and at multiple time points (up to 24 hours) post-infusion and at Day 1 for further cycles up to 54 months (Cycle length=21 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose Escalation and Expansion Phases: CLR: Renal Clearance for TAK-676</measure>
    <time_frame>Dose Escalation and Expansion Phases: Cycle 1 Days 1, 8 and 15: pre-infusion and at multiple time points (up to 24 hours) post-infusion and at Day 1 for further cycles up to 54 months (Cycle length=21 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose Escalation and Expansion Phases: Percentage of Dose Excreted in Urine During 24 Hours After Dosing</measure>
    <time_frame>Dose Escalation and Expansion Phases: Cycle 1 Days 1, 8 and 15: pre-infusion and at multiple time points (up to 24 hours) post-infusion and at Day 1 for further cycles up to 54 months (Cycle length=21 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose Escalation and Expansion Phases: CLR/CL%: Renal Clearance as Percentage of Total Clearance for TAK-676</measure>
    <time_frame>Dose Escalation and Expansion Phases: Cycle 1 Days 1, 8 and 15: pre-infusion and at multiple time points (up to 24 hours) post-infusion and at Day 1 for further cycles up to 54 months (Cycle length=21 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose Escalation and Expansion Phases: Overall Response Rate (ORR)</measure>
    <time_frame>Up to approximately 54 months</time_frame>
    <description>ORR is defined as the percentage of participants who achieve confirmed complete response (cCR) + confirmed partial response (cPR) during the study in response-evaluable population. ORR will be assessed based on Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose Escalation and Expansion Phases: Disease Control Rate (DCR)</measure>
    <time_frame>Up to approximately 54 months</time_frame>
    <description>DCR is defined as the percentage of participants who achieve cCR + cPR + stable disease (SD) greater than (&gt;) 6 weeks during the study in response-evaluable population. The DCR will be assessed based on RECIST v1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose Escalation and Expansion Phases: Duration of Response (DOR)</measure>
    <time_frame>Up to approximately 54 months</time_frame>
    <description>DOR is the time from the date of first documentation of a cPR or better to the date of first documentation of progressive disease for responders (cPR or better). Responders without documentation of progressive disease will be censored at the date of last response assessment that is SD or better. DOR will be assessed based on RECIST v1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose Escalation and Expansion Phases: Time to Response (TTR)</measure>
    <time_frame>Up to approximately 54 months</time_frame>
    <description>TTR is defined as the time from the date of first dose administration to the date of first documented cPR or better by the investigator. TTR will be assessed based on RECIST v1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose Escalation and Expansion Phases: Number of Participants with Upregulation of TAK-676-Induced Stimulator of Interferon Genes (STING)</measure>
    <time_frame>Up to approximately 54 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose Escalation and Expansion Phases: Number of Participants With T-cell Infiltration Upon TAK-676 Treatment</measure>
    <time_frame>Up to approximately 54 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose Escalation and Expansion Phases: Percentage Change from Baseline in the Mutations as per Genomic, Transcriptomic and Protein Expression Analyses of Baseline and On-treatment Tumor Tissue</measure>
    <time_frame>Up to approximately 54 months</time_frame>
  </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 the date of first dose administration to the date of first documented disease progression or death due to any cause, whichever occurs first.</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>
  <secondary_outcome>
    <measure>Expansion Phase Only: OS Rate at 12 Months</measure>
    <time_frame>Up to 24 months</time_frame>
    <description>12-month OS rate is defined as the percentage of participants who are still alive at 12 months from their first dose administration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Expansion Phase Only: OS Rate at 6 Months</measure>
    <time_frame>Up to 24 months</time_frame>
    <description>6-month OS rate is defined as the percentage of participants who are still alive at 6 months from their first dose administration.</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Anticipated">288</enrollment>
  <condition>Solid Neoplasms</condition>
  <arm_group>
    <arm_group_label>Part 1 (Monotherapy Dose Escalation Phase): TAK-676 Safety Lead-in + TAK-676 SA [Part 1A]</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Safety Lead-in: TAK-676 0.1 mg, infusion, intravenously (IV), once weekly, on Days 1, 8 and 15 in 21-day treatment cycles.&#xD;
TAK-676 single agent (SA) Dose Escalation (Part 1A): TAK-676 SA, infusion, IV, once weekly on Days 1, 8 and 15 in each 21-day treatment cycles with escalating doses (0.2 mg and above). The dosing will be initiated in the TAK-676 SA Dose Escalation Phase based on the available safety and tolerability data from the Safety Lead-in.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1B (Combination Dose Escalation Phase): TAK-676 + Pembrolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TAK-676 escalating doses (0.2 mg and above) in combination with pembrolizumab 200 mg, infusion, IV, once weekly on Days 1, 8 and 15 in each 21-day treatment cycle. Pembrolizumab 200 mg will be administered 1 hour prior to TAK-676 once every 3 weeks (Q3W). The dosing will be initiated when at least two dose levels (DLs) of Part 1A have been evaluated.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2A (SCCHN Dose Expansion Phase): TAK-676 + Pembrolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TAK-676 infusion, IV, will be administered in participants with squamous cell carcinoma of head and neck (SCCHN) at the identified dose level from Part 1 on Days 1, 8, and 15 in a 21-day cycle along with pembrolizumab 200 mg infusion, IV, Q3W.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2B (SCCHN Dose Expansion Phase): TAK-676 + Pembrolizumab + Chemotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TAK-676 infusion, IV, will be administered in participants with SCCHN at the identified dose level from Part 1 on Days 1, 8, and 15 in a 21-day cycle. Pembrolizumab infusion, IV will be administered at 200 mg Q3W. Platinum-based chemotherapy comprising the combination of carboplatin (target area under the curve of 5 mg/mL/minute[AUC 5]) or cisplatin (100 milligrams per square meter [mg/m^2] Day 1 of each treatment cycle), and 5-fluorouracil ([5-FU]; 1000 mg/m^2 per day for 4 consecutive days) every 3 weeks for up to 6 cycles.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Experimental: Part 3A (Expansion Phase in CRC): TAK-676 + Pembrolizumab in MSI-H/dMMR CRC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TAK-676, infusion, IV, will be administered in participants with microsatellite instability-high /mismatch repair deficient (MSI-H/dMMR) colorectal cancer (CRC) at the identified dose level from Part 1 on Days 1, 8, and 15 in a 21-day cycle along with pembrolizumab 200 mg infusion, IV, Q3W.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 3B (Expansion Phase in CRC): TAK-676 + Pembrolizumab in MSS/pMMR CRC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TAK-676, infusion, IV, will be administered in participants with microsatellite stable/mismatch repair proficient (MSS/pMMR) CRC at the identified dose level from Part 1 on Days 1, 8, and 15 in a 21-day cycle. along with pembrolizumab 200 mg infusion, IV, Q3W.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TAK-676</intervention_name>
    <description>TAK-676 intravenous Infusion.</description>
    <arm_group_label>Experimental: Part 3A (Expansion Phase in CRC): TAK-676 + Pembrolizumab in MSI-H/dMMR CRC</arm_group_label>
    <arm_group_label>Part 1 (Monotherapy Dose Escalation Phase): TAK-676 Safety Lead-in + TAK-676 SA [Part 1A]</arm_group_label>
    <arm_group_label>Part 1B (Combination Dose Escalation Phase): TAK-676 + Pembrolizumab</arm_group_label>
    <arm_group_label>Part 2A (SCCHN Dose Expansion Phase): TAK-676 + Pembrolizumab</arm_group_label>
    <arm_group_label>Part 2B (SCCHN Dose Expansion Phase): TAK-676 + Pembrolizumab + Chemotherapy</arm_group_label>
    <arm_group_label>Part 3B (Expansion Phase in CRC): TAK-676 + Pembrolizumab in MSS/pMMR CRC</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>Pembrolizumab intravenous Infusion.</description>
    <arm_group_label>Experimental: Part 3A (Expansion Phase in CRC): TAK-676 + Pembrolizumab in MSI-H/dMMR CRC</arm_group_label>
    <arm_group_label>Part 1B (Combination Dose Escalation Phase): TAK-676 + Pembrolizumab</arm_group_label>
    <arm_group_label>Part 2A (SCCHN Dose Expansion Phase): TAK-676 + Pembrolizumab</arm_group_label>
    <arm_group_label>Part 2B (SCCHN Dose Expansion Phase): TAK-676 + Pembrolizumab + Chemotherapy</arm_group_label>
    <arm_group_label>Part 3B (Expansion Phase in CRC): TAK-676 + Pembrolizumab in MSS/pMMR CRC</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Platinum</intervention_name>
    <description>Carboplatin or Cisplatin intravenous infusion</description>
    <arm_group_label>Part 2B (SCCHN Dose Expansion Phase): TAK-676 + Pembrolizumab + Chemotherapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>5-fluorouracil</intervention_name>
    <description>5-fluorouracil intravenous infusion</description>
    <arm_group_label>Part 2B (SCCHN Dose Expansion Phase): TAK-676 + Pembrolizumab + Chemotherapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.&#xD;
&#xD;
          2. TAK-676 SA (dose escalation Part 1A):&#xD;
&#xD;
             o With histologically confirmed (cytological diagnosis is acceptable) advanced or&#xD;
             metastatic solid tumors that have no standard therapeutic options or are intolerant to&#xD;
             these therapies.&#xD;
&#xD;
          3. TAK-676 in combination with pembrolizumab (dose escalation Part 1B):&#xD;
&#xD;
               -  With histologically confirmed (cytological diagnosis is acceptable) advanced or&#xD;
                  metastatic solid tumors that have no standard therapeutic options or are&#xD;
                  intolerant to them, including:&#xD;
&#xD;
               -  Tumors that have relapsed or are refractory to anti-programmed cell death protein&#xD;
                  1 (anti-PD-1)/anti-programmed cell death ligand 1 (anti-PD-L1) therapy.&#xD;
&#xD;
               -  Tumors that are naive to anti-PD-1/ anti-PD-L1 therapy.&#xD;
&#xD;
          4. For expansion phase only:&#xD;
&#xD;
             • SCCHN (Part 2):&#xD;
&#xD;
               -  Participants with histologically confirmed (cytological diagnosis is acceptable)&#xD;
                  metastatic or recurrent, unresectable SCCHN that is considered incurable by local&#xD;
                  therapies. Participants should not have had prior systemic therapy administered&#xD;
                  in the recurrent or metastatic setting. Systemic therapy which was completed more&#xD;
                  than 6 months before signing consent if given as part of multimodal treatment of&#xD;
                  locally advanced disease is allowed.&#xD;
&#xD;
               -  Anatomic subsites to be included are oral cavity, oropharynx, hypopharynx,&#xD;
                  larynx, nasal cavity, and paranasal sinuses (maxillary, ethmoid, sphenoid, and&#xD;
                  frontal). The exception to this is nasopharyngeal cancer and salivary gland&#xD;
                  tumors, which will not be included.&#xD;
&#xD;
               -  Participants with oropharyngeal cancer or tumors arising in the paranasal sinuses&#xD;
                  (maxillary, ethmoid, sphenoid, and frontal) must agree to provide archival tissue&#xD;
                  for human papilloma virus (HPV) testing or if known, HPV testing results using&#xD;
                  CINtec® p16 Histology assay and a 70% cutoff point must be provided. If HPV&#xD;
                  status was previously tested using this method, no additional testing is&#xD;
                  required.&#xD;
&#xD;
               -  For Part 2A, tumors must have a combined positive score (CPS) ≥1. For Part 2B,&#xD;
                  any CPS is eligible.&#xD;
&#xD;
               -  For Part 2B, participants must be eligible to receive treatment with either&#xD;
                  cisplatin or carboplatin in combination with 5-fluorouracil (5-FU) per the&#xD;
                  treating physician.&#xD;
&#xD;
          5. CRC (Part 3):&#xD;
&#xD;
               -  Third-line or later MSI-H/dMMR CRC (Part 3A): Participants with histologically&#xD;
                  confirmed (cytological diagnosis is acceptable) recurrent locally advanced or&#xD;
                  metastatic MSI-H/dMMR CRC whose disease has progressed on or following therapy&#xD;
                  with 1) an anti-PD-1 or PD-L1 antibody (ie, pembrolizumab) and 2) at least one&#xD;
                  line of combination chemotherapy including a fluoropyrimidine and irinotecan OR&#xD;
                  oxaliplatin with or without an anti- epidermal growth factor receptor (EGFR) or&#xD;
                  anti-vascular endothelial growth factor (VEGFR) monoclonal antibody (ie,&#xD;
                  cetuximab or bevacizumab). MSI-H/dMMR CRC participants must have received at&#xD;
                  least 6 weeks of prior treatment with an anti-PD-1 or anti-PD-L1 antibody.&#xD;
&#xD;
               -  Third-line MSS/pMMR CRC (Part 3B): Participants with histologically confirmed&#xD;
                  (cytological diagnosis is acceptable) recurrent locally advanced or metastatic&#xD;
                  MSS/pMMR CRC whose disease has progressed on or following therapy with 2&#xD;
                  different lines of combination chemotherapy, including therapy with a&#xD;
                  fluoropyrimidine and irinotecan AND therapy with a fluoropyrimidine and&#xD;
                  oxaliplatin. Both lines of therapy may be given with or without an anti-EGFR or&#xD;
                  anti-VEGFR monoclonal antibody (ie, cetuximab or bevacizumab). Participants with&#xD;
                  MSS/pMMR CRC must have progressed on or after combination chemotherapy regimens&#xD;
                  containing BOTH irinotecan AND oxaliplatin.&#xD;
&#xD;
               -  Participants with MSI-H/dMMR or MSS/pMMR CRC must have MSI/MMR status confirmed&#xD;
                  by a clinically-approved immunohistochemistry (IHC) and/or polymerase chain&#xD;
                  reaction (PCR) assay.&#xD;
&#xD;
               -  Participants with MSI-H/dMMR or MSS/pMMR CRC must have been treated with 2 prior&#xD;
                  lines of therapy in the recurrent locally advanced or metastatic setting.&#xD;
&#xD;
          6. Adequate bone marrow, renal, hepatic and cardiac functions.&#xD;
&#xD;
          7. Left ventricular ejection fraction (LVEF) &gt;50%, as measured by echocardiogram or&#xD;
             multiple-gated acquisition (MUGA) scan within 4 weeks before receiving the first dose&#xD;
             of study drug.&#xD;
&#xD;
          8. Clinically significant toxic effects of previous therapy have recovered to Grade 1&#xD;
             (per NCI CTCAE Version 5.0) or baseline, except for alopecia, Grade 2 peripheral&#xD;
             neuropathy, and/or autoimmune endocrinopathies with stable endocrine replacement&#xD;
             therapy.&#xD;
&#xD;
          9. In dose escalation Part 1, once peripheral evidence of TAK-676 pharmacodynamic&#xD;
             stimulation of the innate and/or adaptive immune system is observed in the blood&#xD;
             and/or clinical response/partial response (CR/PR) is observed in at least 1&#xD;
             participant, subsequent participants must:&#xD;
&#xD;
               -  Have at least 1 lesion amenable for biopsy.&#xD;
&#xD;
               -  Agree to have 2 tumor biopsies: 1 during the screening period and 1 while on&#xD;
                  TAK-676 treatment.&#xD;
&#xD;
         10. Must have at least 1 RECIST v.1.1-evaluable (measurable) lesion. For the dose&#xD;
             escalation phase (Part 1) only, nonmeasurable only disease is acceptable.&#xD;
&#xD;
         11. Pharmacokinetic (PK)/pharmacodynamic blood must be drawn on a peripherally-inserted&#xD;
             catheter. TAK-676 is preferentially administered through a central line, but&#xD;
             peripheral infusion is acceptable. If a peripheral line is used for TAK-676 and/or&#xD;
             pembrolizumab infusion, it must be separate than the one used for PK/pharmacodynamic&#xD;
             collection.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Corrected QT interval by Fredericia (QTcF) greater than (&gt;) 450 milliseconds (men) or&#xD;
             &gt;475 milliseconds (women) on a 12-lead electrocardiogram (ECG) during the screening&#xD;
             period.&#xD;
&#xD;
          2. Grade greater than or equal to (&gt;=) 2 hypotension (that is, hypotension for which&#xD;
             nonurgent intervention is required) at screening or during Cycle 1 Day 1 (C1D1)&#xD;
             predose assessment.&#xD;
&#xD;
          3. Oxygen saturation less than (&lt;) 92 percent (%) on room air at screening or during C1D1&#xD;
             predose assessment.&#xD;
&#xD;
          4. Treated with other STING agonists/antagonist and toll-like receptors agonists within&#xD;
             the past 6 months.&#xD;
&#xD;
          5. Active vaping within 90 days of C1D1 of study drug(s).&#xD;
&#xD;
          6. Active smoking.&#xD;
&#xD;
          7. Current history of pneumonitis, interstitial lung disease, severe chronic obstructive&#xD;
             pulmonary disease, idiopathic pulmonary fibrosis, other restrictive lung diseases,&#xD;
             acute pulmonary embolism, or Grade &gt;=2 pleural effusion or ascites not controlled by&#xD;
             tap or requiring indwelling catheters.&#xD;
&#xD;
          8. History of brain metastasis unless:&#xD;
&#xD;
               -  Clinically stable (that is, &gt;=6 weeks) after prior surgery, whole-brain&#xD;
                  radiation, or stereotactic radiosurgery, AND&#xD;
&#xD;
               -  Off corticosteroids.&#xD;
&#xD;
          9. Ongoing Grade &gt;= 2 infection or participants with Grade &gt;=2 fever of malignant origin.&#xD;
&#xD;
         10. Chronic, active hepatitis (example: participants with known hepatitis B surface&#xD;
             antigen seropositive and/or detectable hepatitis C virus [HCV]-RNA).&#xD;
&#xD;
         11. For participants in the dose escalation SA Part 1A only: refusal of standard&#xD;
             therapeutic options.&#xD;
&#xD;
         12. For participants receiving pembrolizumab only: contraindication and/or intolerance to&#xD;
             the administration of pembrolizumab.&#xD;
&#xD;
         13. For participants receiving chemotherapy in Part 2B: contraindication and/or&#xD;
             intolerance to the administration of both platinum agents (cisplatin and carboplatin)&#xD;
             and/or 5-FU.&#xD;
&#xD;
         14. Concurrent chemotherapy (except for Part 2B), immunotherapy (except for pembrolizumab&#xD;
             in Part 1B, Part 2, and Part 3), biologic, or hormonal therapy (except for adjuvant&#xD;
             endocrine therapy for a history of breast cancer). Concurrent use of hormones for&#xD;
             noncancer-related conditions is acceptable (except for corticosteroid hormones),&#xD;
             unless allowed per exclusion criterion 16.&#xD;
&#xD;
         15. Radiation therapy within 14 days (42 days for radiation to the lungs) and/or systemic&#xD;
             treatment with radionuclides within 42 days before C1D1 of study drug(s). Participants&#xD;
             with clinically relevant ongoing pulmonary complications from prior radiation therapy&#xD;
             are not eligible.&#xD;
&#xD;
         16. Use of systemic corticosteroids or other immunosuppressive therapy, concurrently or&#xD;
             within 7 days of C1D1 of study drug(s), with the following exceptions:&#xD;
&#xD;
               -  Topical, intranasal, inhaled, ocular, intra-articular, and/or other non-systemic&#xD;
                  corticosteroids.&#xD;
&#xD;
               -  Physiological doses of replacement steroid therapy (example: for adrenal&#xD;
                  insufficiency).&#xD;
&#xD;
               -  For participants enrolled in Part 2B, chemotherapy premedication with steroids&#xD;
                  can be administered according to local standards of care practice.&#xD;
&#xD;
         17. Use of medications that are known clinical organic anion-transporting polypeptide B1&#xD;
             (OATP1B1) and/or OATP1B3 inhibitors, concurrently or within 14 days of C1D1 of study&#xD;
             drug(s).&#xD;
&#xD;
         18. Receipt of live attenuated vaccine (eg, tuberculosis Bacillus Calmette-Guerin vaccine,&#xD;
             oral polio vaccine, measles, rotavirus, yellow fever) within 28 days of C1D1 of study&#xD;
             drug(s).&#xD;
&#xD;
         19. Recipients of allogeneic or autologous stem cell transplantation or organ&#xD;
             transplantation.&#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>Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Takeda</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Takeda Contact</last_name>
    <phone>+1-877-825-3327</phone>
    <email>medinfoUS@takeda.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of California San Diego Moores Cancer Center</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>858-657-7000</phone>
      <email>spatel@ucsd.edu</email>
    </contact>
    <investigator>
      <last_name>Sandip Patel</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>SCRI - HealthOne Denver</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80218</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>720-754-2610</phone>
      <email>gerald.falchook@scresearch.net</email>
    </contact>
    <investigator>
      <last_name>Gerald Falchook</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </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>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>203-785-3333</phone>
      <email>patricia.lorusso@yale.edu</email>
    </contact>
    <investigator>
      <last_name>Patricia LoRusso</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>617-724-4000</phone>
      <email>xgao4@partners.org</email>
    </contact>
    <investigator>
      <last_name>Xin Gao</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Providence Portland Medical Center</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97213</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>503-215-5696</phone>
      <email>rachel.sanborn@providence.org</email>
    </contact>
    <investigator>
      <last_name>Rachel Sanborn</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Fox Chase Cancer Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19111</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>215-214-1676</phone>
      <email>anthony.olszanski@fccc.edu</email>
    </contact>
    <investigator>
      <last_name>Anthony Olszanski</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>773-702-6180</phone>
      <email>lukejj@upmc.edu</email>
    </contact>
    <investigator>
      <last_name>Jason Luke</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Mary Crowley Cancer Research</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75230</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>214-658-1994</phone>
      <email>dorr@marycrowley.org</email>
    </contact>
    <investigator>
      <last_name>Douglas Orr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Princess Margaret Cancer Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Contact</last_name>
      <phone>416-946-4534</phone>
      <email>philippe.bedard@uhn.ca</email>
    </contact>
    <investigator>
      <last_name>Philippe Bedard</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicaltrials.takeda.com/study-detail/5f6b603d4db2bf003ab4a3a7</url>
    <description>To obtain more information on the study, click here/on this link</description>
  </link>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>June 4, 2020</study_first_submitted>
  <study_first_submitted_qc>June 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>October 13, 2022</last_update_submitted>
  <last_update_submitted_qc>October 13, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Drug Therapy</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</mesh_term>
    <mesh_term>Fluorouracil</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_access_criteria>IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.</ipd_access_criteria>
    <ipd_url>https://vivli.org/ourmember/takeda/</ipd_url>
  </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/NCT04420884
org study id: TAK-676-1002
secondary id: U1111-1241-4427
secondary id: 2022-000528-39
nct id: NCT04420884
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The main aim of this study is to check if people with advanced solid tumors have side effects
      from TAK-676, and to check how much TAK-676 they can receive without getting significant side
      effects from it when given alone and in combination with pembrolizumab. The study will be
      conducted in two phases including a dose escalation phase and a dose expansion phase. In the
      dose escalation phase, escalating doses of TAK-676 are being tested alone and in combination
      with pembrolizumab to treat participants who have advanced or metastatic solid tumors. In the
      dose expansion phase, TAK-676 will be studied with pembrolizumab with or without chemotherapy
      in participants with untreated metastatic or recurrent, unresectable squamous cell carcinoma
      of head and neck (SCCHN) and in combination with pembrolizumab in third-line or later
      recurrent locally advanced or metastatic microsatellite instability-high /mismatch repair
      deficient (MSI-H/dMMR) and third-line recurrent locally advanced or metastatic microsatellite
      stable/mismatch repair proficient (MSS/pMMR) colorectal cancer (CRC).
The drug being tested in this study is called TAK-676. TAK-676 is being tested to treat
      people who have advanced or metastatic solid tumors.

      The study will enroll approximately 288 participants. Part 1 consists of an initial Safety
      Lead-in to Dose Escalation Phase; Part 2 and Part 3 compose the Expansion Phase in 2 specific
      indications namely, previously untreated metastatic or recurrent, unresectable SCCHN (Part 2)
      and third-line or later recurrent locally advanced or metastatic MSI-H/dMMR and third-line
      recurrent locally advanced or metastatic MSS/pMMR CRC (Part 3). Participants will be assigned
      to the following treatment groups in the respective Phases of the study:

        -  Part 1 (Dose Escalation Phase): Safety Lead-in + TAK-676 SA [Part 1A] TAK-676 0.1
           milligram (mg) in the Safety Lead-in followed by TAK-676 as escalating doses (0.2 mg and
           above) in Part 1A.

        -  Part 1B (Combination Dose Escalation Phase): TAK-676 as escalating doses (0.2 mg and
           above) + Pembrolizumab

      Once a safe and effective dose is recommended from Part 1, participants of select advanced or
      metastatic solid tumors will receive TAK-676 in below defined cohorts in the expansion phase:

        -  Part 2A (SCCHN Dose Expansion Phase): TAK-676 + Pembrolizumab

        -  Part 2B (SCCHN Dose Expansion Phase): TAK-676 + Pembrolizumab + Chemotherapy

        -  Part 3A (Expansion Phase in CRC): TAK-676 + Pembrolizumab in MSI-H/dMMR CRC

        -  Part 3B (Expansion Phase in CRC): TAK-676 + Pembrolizumab in MSS/pMMR CRC

      This multi-center trial will be conducted worldwide. The overall time to participate in this
      study is 54 months. Participants will make multiple visits to the clinic, including 30 days
      after last dose of study drug for a follow-up assessment. Patients in Parts 2 and 3 will be
      followed for survival for up to 12 months after the last dose of study drug.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants Reporting one or More Treatment-emergent Adverse Events (TEAEs) and Based on TEAEs Severity
time frame: Up to approximately 54 months
description: A severity grade is defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0. 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: Number of Participants with Dose-Limiting Toxicities (DLTs)
time frame: Up to approximately 54 months
description: A DLT will be defined as any of the TEAEs, but not limited to, those that occur during Cycle 1 and are considered by the investigator to be at least possibly related to TAK-676 as a single agent (SA) or in combination with pembrolizumab. TEAEs meeting DLT definitions occurring in Cycle 2 or later will be considered in the determination of the recommended phase 2 dose (RP2D) of TAK-676, both in the TAK-676 SA and the combination with pembrolizumab arms. Toxicity will be evaluated according to NCI CTCAE version 5.0.
measure: Number of Participants Reporting One or More Treatment Emergent Serious Adverse Event (SAEs)
time frame: Up to approximately 54 months
measure: Number of Participants With one or More TEAEs Leading to Dose Modifications and Treatment Discontinuations
time frame: Up to approximately 54 months
measure: Dose Escalation and Expansion Phases: Cmax: Maximum Observed Plasma Concentration for TAK-676
time frame: Dose Escalation and Expansion Phases: Cycle 1 Days 1, 8 and 15: pre-infusion and at multiple time points (up to 24 hours) post-infusion and at Day 1 for further cycles up to 54 months (Cycle length=21 days)
measure: Dose Escalation and Expansion Phases: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-676
time frame: Dose Escalation and Expansion Phases: Cycle 1 Days 1, 8 and 15: pre-infusion and at multiple time points (up to 24 hours) post-infusion and at Day 1 for further cycles up to 54 months (Cycle length=21 days)
measure: Dose Escalation and Expansion Phases: AUCt: Area Under the Concentration-time Curve From Time 0 to Time t for TAK-676
time frame: Dose Escalation and Expansion Phases: Cycle 1 Days 1, 8 and 15: pre-infusion and at multiple time points (up to 24 hours) post-infusion and at Day 1 for further cycles up to 54 months (Cycle length=21 days)
measure: Dose Escalation and Expansion Phases: AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity for TAK-676
time frame: Dose Escalation and Expansion Phases: Cycle 1 Days 1, 8 and 15: pre-infusion and at multiple time points (up to 24 hours) post-infusion and at Day 1 for further cycles up to 54 months (Cycle length=21 days)
measure: Dose Escalation and Expansion Phases: t1/2z: Terminal Disposition Phase Half-life for TAK-676
time frame: Dose Escalation and Expansion Phases: Cycle 1 Days 1, 8 and 15: pre-infusion and at multiple time points (up to 24 hours) post-infusion and at Day 1 for further cycles up to 54 months (Cycle length=21 days)
measure: Dose Escalation and Expansion Phases: CL: Total Clearance After Intravenous Administration for TAK-676
time frame: Dose Escalation and Expansion Phases: Cycle 1 Days 1, 8 and 15: pre-infusion and at multiple time points (up to 24 hours) post-infusion and at Day 1 for further cycles up to 54 months (Cycle length=21 days)
measure: Dose Escalation and Expansion Phases: Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-676
time frame: Dose Escalation and Expansion Phases: Cycle 1 Days 1, 8 and 15: pre-infusion and at multiple time points (up to 24 hours) post-infusion and at Day 1 for further cycles up to 54 months (Cycle length=21 days)
measure: Dose Escalation and Expansion Phases: CLR: Renal Clearance for TAK-676
time frame: Dose Escalation and Expansion Phases: Cycle 1 Days 1, 8 and 15: pre-infusion and at multiple time points (up to 24 hours) post-infusion and at Day 1 for further cycles up to 54 months (Cycle length=21 days)
measure: Dose Escalation and Expansion Phases: Percentage of Dose Excreted in Urine During 24 Hours After Dosing
time frame: Dose Escalation and Expansion Phases: Cycle 1 Days 1, 8 and 15: pre-infusion and at multiple time points (up to 24 hours) post-infusion and at Day 1 for further cycles up to 54 months (Cycle length=21 days)
measure: Dose Escalation and Expansion Phases: CLR/CL%: Renal Clearance as Percentage of Total Clearance for TAK-676
time frame: Dose Escalation and Expansion Phases: Cycle 1 Days 1, 8 and 15: pre-infusion and at multiple time points (up to 24 hours) post-infusion and at Day 1 for further cycles up to 54 months (Cycle length=21 days)
measure: Dose Escalation and Expansion Phases: Overall Response Rate (ORR)
time frame: Up to approximately 54 months
description: ORR is defined as the percentage of participants who achieve confirmed complete response (cCR) + confirmed partial response (cPR) during the study in response-evaluable population. ORR will be assessed based on Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1.
measure: Dose Escalation and Expansion Phases: Disease Control Rate (DCR)
time frame: Up to approximately 54 months
description: DCR is defined as the percentage of participants who achieve cCR + cPR + stable disease (SD) greater than (>) 6 weeks during the study in response-evaluable population. The DCR will be assessed based on RECIST v1.1.
measure: Dose Escalation and Expansion Phases: Duration of Response (DOR)
time frame: Up to approximately 54 months
description: DOR is the time from the date of first documentation of a cPR or better to the date of first documentation of progressive disease for responders (cPR or better). Responders without documentation of progressive disease will be censored at the date of last response assessment that is SD or better. DOR will be assessed based on RECIST v1.1.
measure: Dose Escalation and Expansion Phases: Time to Response (TTR)
time frame: Up to approximately 54 months
description: TTR is defined as the time from the date of first dose administration to the date of first documented cPR or better by the investigator. TTR will be assessed based on RECIST v1.1.
measure: Dose Escalation and Expansion Phases: Number of Participants with Upregulation of TAK-676-Induced Stimulator of Interferon Genes (STING)
time frame: Up to approximately 54 months
measure: Dose Escalation and Expansion Phases: Number of Participants With T-cell Infiltration Upon TAK-676 Treatment
time frame: Up to approximately 54 months
measure: Dose Escalation and Expansion Phases: Percentage Change from Baseline in the Mutations as per Genomic, Transcriptomic and Protein Expression Analyses of Baseline and On-treatment Tumor Tissue
time frame: Up to approximately 54 months
measure: Expansion Phase Only: Progression-Free Survival (PFS)
time frame: Up to approximately 24 months
description: PFS is defined as the time from the date of first dose administration to the date of first documented disease progression or death due to any cause, whichever occurs first.
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.
measure: Expansion Phase Only: OS Rate at 12 Months
time frame: Up to 24 months
description: 12-month OS rate is defined as the percentage of participants who are still alive at 12 months from their first dose administration.
measure: Expansion Phase Only: OS Rate at 6 Months
time frame: Up to 24 months
description: 6-month OS rate is defined as the percentage of participants who are still alive at 6 months from their first dose administration.
arm group label: Part 1 (Monotherapy Dose Escalation Phase): TAK-676 Safety Lead-in + TAK-676 SA [Part 1A]
arm group type: Experimental
description: Safety Lead-in: TAK-676 0.1 mg, infusion, intravenously (IV), once weekly, on Days 1, 8 and 15 in 21-day treatment cycles.
TAK-676 single agent (SA) Dose Escalation (Part 1A): TAK-676 SA, infusion, IV, once weekly on Days 1, 8 and 15 in each 21-day treatment cycles with escalating doses (0.2 mg and above). The dosing will be initiated in the TAK-676 SA Dose Escalation Phase based on the available safety and tolerability data from the Safety Lead-in.
arm group label: Part 1B (Combination Dose Escalation Phase): TAK-676 + Pembrolizumab
arm group type: Experimental
description: TAK-676 escalating doses (0.2 mg and above) in combination with pembrolizumab 200 mg, infusion, IV, once weekly on Days 1, 8 and 15 in each 21-day treatment cycle. Pembrolizumab 200 mg will be administered 1 hour prior to TAK-676 once every 3 weeks (Q3W). The dosing will be initiated when at least two dose levels (DLs) of Part 1A have been evaluated.
arm group label: Part 2A (SCCHN Dose Expansion Phase): TAK-676 + Pembrolizumab
arm group type: Experimental
description: TAK-676 infusion, IV, will be administered in participants with squamous cell carcinoma of head and neck (SCCHN) at the identified dose level from Part 1 on Days 1, 8, and 15 in a 21-day cycle along with pembrolizumab 200 mg infusion, IV, Q3W.
arm group label: Part 2B (SCCHN Dose Expansion Phase): TAK-676 + Pembrolizumab + Chemotherapy
arm group type: Experimental
description: TAK-676 infusion, IV, will be administered in participants with SCCHN at the identified dose level from Part 1 on Days 1, 8, and 15 in a 21-day cycle. Pembrolizumab infusion, IV will be administered at 200 mg Q3W. Platinum-based chemotherapy comprising the combination of carboplatin (target area under the curve of 5 mg/mL/minute[AUC 5]) or cisplatin (100 milligrams per square meter [mg/m^2] Day 1 of each treatment cycle), and 5-fluorouracil ([5-FU]; 1000 mg/m^2 per day for 4 consecutive days) every 3 weeks for up to 6 cycles.
arm group label: Experimental: Part 3A (Expansion Phase in CRC): TAK-676 + Pembrolizumab in MSI-H/dMMR CRC
arm group type: Experimental
description: TAK-676, infusion, IV, will be administered in participants with microsatellite instability-high /mismatch repair deficient (MSI-H/dMMR) colorectal cancer (CRC) at the identified dose level from Part 1 on Days 1, 8, and 15 in a 21-day cycle along with pembrolizumab 200 mg infusion, IV, Q3W.
arm group label: Part 3B (Expansion Phase in CRC): TAK-676 + Pembrolizumab in MSS/pMMR CRC
arm group type: Experimental
description: TAK-676, infusion, IV, will be administered in participants with microsatellite stable/mismatch repair proficient (MSS/pMMR) CRC at the identified dose level from Part 1 on Days 1, 8, and 15 in a 21-day cycle. along with pembrolizumab 200 mg infusion, IV, Q3W.
intervention type: Drug
intervention name: TAK-676
description: TAK-676 intravenous Infusion.
arm group label: Experimental: Part 3A (Expansion Phase in CRC): TAK-676 + Pembrolizumab in MSI-H/dMMR CRC
arm group label: Part 1 (Monotherapy Dose Escalation Phase): TAK-676 Safety Lead-in + TAK-676 SA [Part 1A]
arm group label: Part 1B (Combination Dose Escalation Phase): TAK-676 + Pembrolizumab
arm group label: Part 2A (SCCHN Dose Expansion Phase): TAK-676 + Pembrolizumab
arm group label: Part 2B (SCCHN Dose Expansion Phase): TAK-676 + Pembrolizumab + Chemotherapy
arm group label: Part 3B (Expansion Phase in CRC): TAK-676 + Pembrolizumab in MSS/pMMR CRC
intervention type: Drug
intervention name: Pembrolizumab
description: Pembrolizumab intravenous Infusion.
arm group label: Experimental: Part 3A (Expansion Phase in CRC): TAK-676 + Pembrolizumab in MSI-H/dMMR CRC
arm group label: Part 1B (Combination Dose Escalation Phase): TAK-676 + Pembrolizumab
arm group label: Part 2A (SCCHN Dose Expansion Phase): TAK-676 + Pembrolizumab
arm group label: Part 2B (SCCHN Dose Expansion Phase): TAK-676 + Pembrolizumab + Chemotherapy
arm group label: Part 3B (Expansion Phase in CRC): TAK-676 + Pembrolizumab in MSS/pMMR CRC
intervention type: Drug
intervention name: Platinum
description: Carboplatin or Cisplatin intravenous infusion
arm group label: Part 2B (SCCHN Dose Expansion Phase): TAK-676 + Pembrolizumab + Chemotherapy
intervention type: Drug
intervention name: 5-fluorouracil
description: 5-fluorouracil intravenous infusion
arm group label: Part 2B (SCCHN Dose Expansion Phase): TAK-676 + Pembrolizumab + Chemotherapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Study Director
role: Study Director
affiliation: Takeda
last name: Takeda Contact
phone: +1-877-825-3327
email: medinfoUS@takeda.com
facility: 
status: Recruiting
contact: 
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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country: Canada
country: United States
url: https://clinicaltrials.takeda.com/study-detail/5f6b603d4db2bf003ab4a3a7
description: To obtain more information on the study, click here/on this link
responsible party type: Sponsor
mesh term: Pembrolizumab
mesh term: Fluorouracil
sharing ipd: Yes
ipd description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd access criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
ipd url: https://vivli.org/ourmember/takeda/