Clinical Trials /

A Study of TAK-981 in Participants With Relapsed/Refractory Solid Tumors or Non-Hodgkin Lymphoma (NHL)

NCT03648372

Description:

This study is in 2 parts. The main aims of the 1st part of the study are to check if people with advanced solid tumors or cancers in the immune system (lymphomas) have side effects from TAK-981, and to check how much TAK-981 they can receive without getting side effects from it. The main aims of the 2nd part of the study are to learn if the condition of people with specific cancers improves after treatment with TAK-981. Another aim is to check for side effects from TAK-981. In the 1st part of the study, participants will receive TAK-981. In the 2nd part of the study, participants with specific tumor types will receive TAK-981 at the recommended phase 2 dose determined during the 1st part of the study. In both parts of the study, participants can receive TAK-981 for up to 1 year or longer if their condition stays improved.

Related Conditions:
  • Colorectal Carcinoma
  • Lymphoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study to Evaluate the Safety, Tolerability, Preliminary Efficacy and Pharmacokinetics (PK) of TAK-981 in Adult Participants With Advanced or Metastatic Solid Tumors or Relapsed/Refractory Hematologic Malignancies and in a Subset With Coronavirus Disease 2019 (COVID-19)
  • Official Title: An Open Label, Dose-Escalation, Phase I Study to Evaluate the Safety, Tolerability, Preliminary Efficacy and Pharmacokinetics of TAK-981 in Adult Patients With Advanced or Metastatic Solid Tumors or Relapsed/Refractory Hematologic Malignancies and in a Subset With Coronavirus Disease 2019

Clinical Trial IDs

  • ORG STUDY ID: TAK-981-1002
  • SECONDARY ID: U1111-1214-4537
  • SECONDARY ID: 2020-003947-27
  • NCT ID: NCT03648372

Conditions

  • Neoplasms
  • Lymphoma
  • Hematologic Neoplasms
  • Coronavirus Disease

Interventions

DrugSynonymsArms
TAK-981COVID-19 Expansion: TAK-981
Standard of careCOVID-19 Expansion: TAK-981

Purpose

The primary objective of this study is to determine the safety and tolerability of TAK-981 as a single agent in participants with advanced or metastatic solid tumors and lymphomas in Phase 1, to evaluate preliminary efficacy of TAK-981 in participants with select solid tumors or relapsed/refractory CD20-positive (CD20+) non-hodgkin lymphoma (NHL) indications in Phase 2, and to assess change in severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) viral load within 8 days of TAK-981 administration in COVID-19 Expansion.

Detailed Description

      01-Oct-2020 Enrollment of participants into the COVID arm of this study is no longer
      recruiting.

      The drug being tested in this study is called TAK-981. TAK-981 is being tested to evaluate
      safety, tolerability, preliminary efficacy and PK in participants with advanced or metastatic
      solid tumors or relapsed/refractory hematologic malignancies and in a subset with COVID-19.
      The study will include 2 phases: Phase 1 dose escalation and Phase 2 dose expansion cohorts
      (cancer treatment expansions and COVID-19 expansion).

      The study will enroll approximately 242 participants, approximately 50 participants in the
      dose escalation phase, approximately 132 participants in cancer treatment expansion phase and
      approximately 60 participants in the COVID-19 expansion.

      In the dose escalation, dose levels will be escalated based on safety, and available PK and
      pharmacodynamic data and will also determine the single agent RP2D. Participants in dose
      expansion phase will be enrolled, once RP2D is determined. There will be 6 cohorts in cancer
      treatment expansions as following:

        -  Cohort A: Nonsquamous NSCLC

        -  Cohort B: Cervical cancer

        -  Cohort C: MSS-CRC

        -  Cohort D: Relapsed/refractory DLBCL progressed or relapsed after CAR T-cells therapy

        -  Cohort E: Relapsed/refractory DLBCL that have not received prior therapy with CAR
           T-cells

        -  Cohort F: Relapsed/refractory FL

      In the COVID-19 expansion, dose schedule can be modified in safety lead-in if PK,
      pharmacodynamics, decrease in viral load and safety data are supportive. Once the safety
      lead-in is complete and a TAK-981 dose and regimen is selected, randomized COVID-19 proof of
      concept will begin with participants randomized to Arm A: COVID-19 standard of care (SOC), or
      Arm B: COVID-19 SOC + TAK-981.

      This multi-center trial will be conducted in the United States and Canada. The overall time
      to participate in this study is approximately 4 years. The overall time to receive treatment
      in the dose escalation and cancer treatment is approximately 1 year and in COVID-19
      expansion, participants will receive 1 cycle of treatment and will be followed for up to 90
      days from enrollment. Based on decision of sponsor, participants with demonstrated clinical
      benefit can continue treatment beyond 1 year. Participants will make multiple visits to the
      clinic, and will make a final visit 30 days after receiving their last dose of drug or before
      the start of subsequent anticancer therapy, whichever occurs first for a follow-up
      assessment.
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1, Dose Escalation Cohort: TAK-981ExperimentalTAK-981, intravenously, administered as 60 minute-infusion, once on Days 1, 4, 8, and 11 in a 21-day treatment cycle for up to approximately 12 months or until discontinuation from the study. If clinical safety, pharmacokinetics, and pharmacodynamics are supportive, the dosing schedule may be modified to evaluate a less intensive administration of TAK-981 on Day 1 or Days 1 and 8 in 21-day cycles in participants with advanced or metastatic solid tumors or lymphomas. Dose levels will be escalated based on the Bayesian logistic regression modeling (BLRM). The dose escalation phase will determine the RP2D of TAK-981.
  • TAK-981
Phase 2, Cohort A: Nonsquamous NSCLCExperimentalTAK-981 at RP2D and schedule, intravenously, administered as 60 minute-infusion in a 21-day treatment cycle for up to approximately 12 months or until discontinuation from the study in participants with nonsquamous non-small cell lung cancer (NSCLC).
  • TAK-981
Phase 2, Cohort B: Cervical CancerExperimentalTAK-981 at RP2D and schedule, intravenously, administered as 60 minute-infusion in a 21-day treatment cycle for up to approximately 12 months or until discontinuation from the study in participants with cervical cancer.
  • TAK-981
Phase 2, Cohort C: MSS-CRCExperimentalTAK-981 at RP2D and schedule, intravenously, administered as 60 minute-infusion in a 21-day treatment cycle for up to approximately 12 months or until discontinuation from the study in participants with microsatellite-stable colorectal cancer (MSS-CRC).
  • TAK-981
Phase 2, Cohort D: r/r DLBCL after CAR T-cells therapyExperimentalTAK-981 at RP2D and schedule, intravenously, administered as 60 minute-infusion in a 21-day treatment cycle for up to approximately 12 months or until discontinuation from the study in participants with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) after prior chimeric antigen receptor (CAR) T-cells therapy.
  • TAK-981
Phase 2, Cohort E: r/r DLBCL without prior CAR T-cells therapyExperimentalTAK-981 at RP2D and schedule, intravenously, administered as 60 minute-infusion in a 21-day treatment cycle for up to approximately 12 months or until discontinuation from the study in participants with relapsed/refractory DLBCL that have not received prior CAR T-cells therapy.
  • TAK-981
Phase 2, Cohort F: r/r Follicular LymphomaExperimentalTAK-981 at RP2D and schedule, intravenously, administered as 60 minute-infusion in a 21-day treatment cycle for up to approximately 12 months or until discontinuation from the study in participants with relapsed/refractory follicular lymphoma (FL).
  • TAK-981
COVID-19 Expansion: TAK-981ExperimentalCovid-19 safety lead-in: TAK-981, intravenously, administered as 60 minute-infusion, once on Days 1 and 4. The starting dose of TAK-981 will be 60 milligram (mg). The initial dosing schedule for COVID-19 expansion cohorts will be for a single cycle with TAK-981 administered on Days 1 and 4. If PK, pharmacodynamics, decrease in viral load and safety data are supportive, the schedule can be modified in safety lead-in. A ramp-up schedule of TAK-981, intravenously, administered as 60 minute-infusion, 40 mg on Day 1 and 60 mg on Day 4 may be evaluated. COVID-19 proof of concept: Once the safety lead-in is complete and a TAK-981 dose and regimen is selected by the Safety Monitoring Committee (SMC), the randomized COVID-19 proof of concept will begin with participants randomized to Arm A: COVID-19 standard of care (SOC), or Arm B: COVID-19 SOC + TAK-981.
  • TAK-981
  • Standard of care

Eligibility Criteria

        Inclusion Criteria:

          1. Adult male or female participants >=18 years old.

          2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 (ECOG 0 to 2,
             for COVID-19 expansion).

          3. Population for Phase 1 dose escalation:

               -  Has histologically or cytologically confirmed advanced (local regionally
                  recurrent not amenable to curative therapy) or metastatic solid tumors who have
                  no standard therapeutic option with a proven clinical benefit, are intolerant, or
                  have refused them. OR

               -  Has relapsed/refractory lymphoma not amenable to therapies with proven clinical
                  benefit or who are intolerant or who refuse them. Participants with low-grade
                  lymphomas such as FL, small lymphocytic lymphoma, lymphoplasmacytoid lymphoma,
                  and marginal zone lymphomas, may not need to exhaust all available therapy. These
                  participants can be enrolled after failure of at least 2 prior systemic
                  therapies, provided that there is not an immediate need for cytoreduction. In
                  these cases, participants who need immediate therapy for tumor bulk are not
                  eligible for this trial.

          4. Population for Phase 2 dose expansion cohorts:

             o Has histologically or cytologically documented, advanced (metastatic and/or
             unresectable) cancer as listed below, that is incurable and for which prior standard
             first-line treatment has failed: Note: Prior neoadjuvant or adjuvant therapy included
             in initial treatment may not be considered first- or later-line SOC treatment unless
             such treatments were completed less than 12 months before the current tumor
             recurrence.

             o Nonsquamous NSCLC that has progressed to 1 prior systemic immune checkpoint
             inhibitors (CPI)/anti-PD-(1/L1)-containing therapy and no more than 2 lines of
             therapy. Participants must have not shown evidence of tumor progression during the
             first 5 months of treatment with first-line CPI/anti-PD-(1/L1)-containing therapy
             (cohort A).

             Note: Participants with known driver mutations/genomic aberrations (example- epidermal
             growth factor receptor [EGFR], B-Raf proto-oncogene mutation V600E [BRAF V600E], and
             ROS proto-oncogene 1 [ROS1] sensitizing mutations, neurotrophic receptor tyrosine
             kinase [NRTK] gene fusions, and anaplastic lymphoma kinase [ALK] rearrangements) must
             have also shown progressive disease after treatment with a commercially available
             targeted therapy.

             o CPI-naïve cervical cancer (squamous cell carcinoma, adenosquamous carcinoma or
             adenocarcinoma of the cervix) participants who have received no more than 1 prior
             systemic line of therapy for recurrent or Stage IVB cervical cancer (cohort B).

             Note: The following cervical tumors are not eligible: minimal deviation/adenoma
             malignum, gastric-type adenocarcinoma, clear-cell carcinoma, and mesonephric
             carcinoma. Histologic confirmation of the original primary tumor is required via
             pathology report.

             Note: First-line treatment must have consisted of platinum-containing doublet.
             Chemotherapy administered concurrently with primary radiation (example- weekly
             cisplatin) is not counted as a systemic chemotherapy regimen.

             o CPI-naïve MSS-CRC participants who have progressed on no more than 3 chemotherapy
             regimens (cohort C).

             Note: Participants must have received prior treatment with fluoropyrimidine-,
             oxaliplatin-, and irinotecan-containing regimens if indicated.

               -  Relapsed/refractory DLBCL progressed or relapsed after prior CAR T cell therapy
                  that has received approval by a health authority for the treatment of DLBCL
                  (cohort D).

               -  Relapsed/refractory DLBCL that has progressed or relapsed after at least 2 but no
                  more than 3 prior lines of systemic therapy and has not received prior cellular
                  therapy. At least one prior line of therapy must have included a CD20-targeted
                  therapy (cohort E).

               -  Relapsed/refractory FL that has progressed or relapsed after at least 2 but no
                  more than 3 prior lines of systemic therapy. At least 1 prior line of therapy
                  must have included a CD20-targeted therapy (cohort F).

          5. In Phase 2 only, have at least 1 radiologically measurable lesion based on RECIST v1.1
             for participants with solid tumors or Lugano criteria for lymphoma. Tumor lesions
             situated in a previously irradiated area are considered measurable if progression has
             been demonstrated in such lesions.

             Note: In Phase 2 stage 1, have an additional lesion for pretreatment and on-treatment
             biopsy.

          6. In Phase 2 stage 1, willing to consent to mandatory pretreatment and on-treatment
             tumor biopsy.

             Note: For fresh tumor biopsies, the lesion must be accessible for a biopsy procedure
             as assessed by the investigator.

          7. Is willing to provide archival tumor tissue sample, if available. (Note: not
             applicable for participants in the COVID-19 expansion.)

          8. COVID-19 expansion:

               -  Has a current histologically confirmed locally advanced or metastatic solid tumor
                  or relapsed/refractory hematologic malignancy.

               -  Has a documented positive result for SARS-CoV-2 RNA in a respiratory specimen by
                  local test that has been analytically validated per local authority guidelines.

               -  Is currently hospitalized (<=3 days before enrollment) for treatment of COVID-19.

               -  Has peripheral capillary oxygen saturation (SpO2) >93 percentage (%) on room air
                  at screening.

               -  Has moderate disease (NEWS <=6).

               -  Has left ventricular ejection fraction (LVEF) >=40%; as measured by
                  echocardiogram or multiple gated acquisition (MUGA) scan within the previous 3
                  months. Note: required for participants with history of significant
                  cardiovascular (CV) disease or history of cardiotoxic therapy.

          9. Adequate bone marrow reserve and renal and hepatic function.

         10. Recovered to Grade 1 or baseline or established as sequelae from all toxic effects of
             previous therapy (except alopecia, neuropathy, or autoimmune endocrinopathies with
             stable endocrine replacement therapy, bone marrow parameters [any of Grade 1 or 2
             permitted if directly related to bone marrow involvement).

         11. Consented to undergo serial skin punch biopsies (dose escalation only).

         12. Suitable venous access for safe drug administration and the study-required PK and
             pharmacodynamics sampling.

         13. Women of childbearing potential participating in this study should avoid becoming
             pregnant, and male participants should avoid impregnating a female partner.
             Nonsterilized female participants of reproductive age and male participants should use
             effective methods of contraception through defined periods during and after study
             treatment as specified below. Female participants must meet 1 of the following:

               -  Postmenopausal for at least 1 year before the screening visit, or

               -  Surgically sterile, or

               -  If they are of childbearing potential, agree to practice 1 highly effective
                  method and 1 additional effective (barrier) method of contraception at the same
                  time, from the time of signing of the informed consent form (ICF) through 90 days
                  after the last dose of study drug (whichever is longer), or

               -  Agree to practice true abstinence, when this is in line with the preferred and
                  usual lifestyle of the participant. (Periodic abstinence [example, calendar,
                  ovulation, symptothermal, postovulation methods], withdrawal, spermicides only,
                  and lactational amenorrhea are not acceptable methods of contraception. Female
                  and male condoms should not be used together.)

         14. Male participants, even if surgically sterilized (that is, status postvasectomy) must
             agree to 1 of the following:

               -  Agree to practice effective barrier contraception during the entire study
                  treatment period and through 120 days after the last dose of study drug, or

               -  Agree to practice true abstinence, when this is in line with the preferred and
                  usual lifestyle of the participant. (Periodic abstinence [example, calendar,
                  ovulation, symptothermal, postovulation methods], withdrawal, spermicides only,
                  and lactational amenorrhea are not acceptable methods of contraception. Female
                  and male condoms should not be used together.)

        Exclusion Criteria:

          1. Phase 1 dose escalation and Phase 2 cancer treatment expansion cohorts:

             o Has received treatment with systemic anticancer treatments or investigational
             products within 14 days before the first dose of study drug or 5 half-lives, whichever
             is shorter.

             Note: Low-dose steroids (oral prednisone or equivalent <=20 mg per day), hormonal
             therapy for prostate cancer or breast cancer (as adjuvant treatment), and treatment
             with bisphosphonates and receptor activator of nuclear factor kappa-Β ligand (RANKL)
             inhibitors are allowed.

             o Has received extended field radiotherapy <=4 weeks before the start of treatment
             (<=2 weeks for limited field radiation for palliation), and who has not recovered to
             grade 1 or baseline from related side effects of such therapy (except for alopecia).

          2. COVID-19 expansion:

               -  Concurrent treatment with other agents with actual or possible direct acting
                  antiviral activity against SARS-CoV-2 is prohibited less than (<) 24 hours prior
                  to study drug dosing.

               -  Require mechanical ventilation or admission to intensive care unit (ICU) at
                  screening.

               -  Require the use of drugs known to prolong QTc interval, , or drugs that are of
                  continuous use and were introduced at least 1 month before enrollment without
                  evidence of QTc prolongation.

          3. History of any of the following <=6 months before first dose: congestive heart failure
             New York Heart Association Grade III or IV, unstable angina, myocardial infarction,
             unstable symptomatic ischemic heart disease, severe noncompensated hypertension
             despite appropriate medical therapy, ongoing symptomatic cardiac arrhythmias of >Grade
             2, pulmonary embolism, or symptomatic cerebrovascular events, or any other serious
             cardiac condition (example, pericardial effusion or restrictive cardiomyopathy).
             Chronic atrial fibrillation on stable anticoagulant therapy is allowed.

          4. Baseline prolongation of the QT interval with Fridericia correction method (QTcF)
             (example, repeated demonstration of QTcF interval >480 milliseconds (ms), history of
             congenital long QT syndrome, or torsades de pointes).

          5. Psychiatric illness/social circumstances that would limit compliance with study
             requirements and substantially increase the risk of adverse events (AEs) or has
             compromised ability to provide written informed consent.

          6. Admission or evidence of illicit drug use, drug abuse, or alcohol abuse.

          7. History of autoimmune disease requiring systemic immunosuppressive therapy.

          8. History of immune-related AEs related to treatment with immune checkpoint inhibitors
             that required treatment discontinuation.

          9. History of noninfectious pneumonitis that required steroids or a history of
             interstitial lung disease.

         10. Has evidence of active, noninfectious pneumonitis.

         11. Have a significant active infection, except participants with SARS-CoV-2 infection in
             the COVID-19 expansion.

         12. Known history of human immunodeficiency virus (HIV) infection or any other relevant
             congenital or acquired immunodeficiency.

         13. Known hepatitis B virus (HBV) surface antigen seropositive or detectable hepatitis C
             infection viral load. Note: Participants who have positive hepatitis B core antibody
             or hepatitis B surface antigen antibody can be enrolled but must have an undetectable
             hepatitis B viral load.

         14. Receiving or requiring the continued use of medications that are known to be strong or
             moderate inhibitors and inducers of cytochrome P-450 3A4/5 (CYP3A4/5) or are strong
             permeability glycoprotein (P-gp) inhibitors. To participate in this study, such
             participants should discontinue use of such agents for at least 2 weeks before
             receiving a dose of TAK-981.

         15. Participant requires the use of drugs known to prolong QTc interval (during Phase 1
             only).

         16. History of allogeneic tissue or solid organ transplant.

         17. Second malignancy within the previous 3 years, except treated basal cell or localized
             squamous skin carcinomas, localized prostate cancer, cervical carcinoma in situ,
             resected colorectal adenomatous polyps, breast cancer in situ, or other malignancy for
             which the participant is not on active anticancer therapy.

         18. Female participants who are lactating and breastfeeding or have a positive serum
             pregnancy test during the screening period or a positive urine pregnancy test on Day 1
             before first dose of study drug.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1: Number of Participants Reporting one or More Treatment Emergent Adverse Events (TEAEs)
Time Frame:Up to 48 months
Safety Issue:
Description:Severity grade will be evaluated as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0, except for Cytokine Release Syndrome (CRS), which will be assessed by American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading criteria.

Secondary Outcome Measures

Measure:Phase 2: Number of Participants Reporting one or More TEAEs
Time Frame:Up to 48 months
Safety Issue:
Description:
Measure:Phase 2: Number of Participants Based on Severity of TEAEs
Time Frame:Up to 48 months
Safety Issue:
Description:Severity grade will be evaluated as per the NCI CTCAE Version 5.0, except for CRS, which will be assessed by ASTCT consensus grading criteria.
Measure:Phase 2, Cmax: Maximum Observed Plasma Concentration for TAK-981
Time Frame:Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post dose; Cycle 1 Day 8 pre-dose and at multiple time points (up to 24 hours) post dose (Cycle length is equal to [=] 21 days)
Safety Issue:
Description:
Measure:Phase 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-981
Time Frame:Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post dose; Cycle 1 Day 8 pre-dose and at multiple time points (up to 24 hours) post dose (Cycle length =21 days)
Safety Issue:
Description:
Measure:Phase 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981
Time Frame:Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post dose; Cycle 1 Day 8 pre-dose and at multiple time points (up to 24 hours) post dose (Cycle length =21 days)
Safety Issue:
Description:
Measure:Phase 2, AUC∞: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for TAK-981
Time Frame:Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post dose; Cycle 1 Day 8 pre-dose and at multiple time points (up to 24 hours) post dose (Cycle length =21 days)
Safety Issue:
Description:
Measure:Phase 2, Terminal Disposition Phase Half-life (t1/2z) for TAK-981
Time Frame:Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post dose; Cycle 1 Day 8 pre-dose and at multiple time points (up to 24 hours) post dose (Cycle length =21 days)
Safety Issue:
Description:
Measure:Phase 2, Total Clearance (CL) After Intravenous Administration for TAK-981
Time Frame:Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post dose; Cycle 1 Day 8 pre-dose and at multiple time points (up to 24 hours) post dose (Cycle length =21 days)
Safety Issue:
Description:
Measure:Phase 2, Volume of Distribution at Steady State After Intravenous Administration (Vss) for TAK-981
Time Frame:Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post dose; Cycle 1 Day 8 pre-dose and at multiple time points (up to 24 hours) post dose (Cycle length =21 days)
Safety Issue:
Description:
Measure:Phase 2: ORR
Time Frame:From the first dose until best response is achieved (up to 4 years)
Safety Issue:
Description:ORR is defined as percentage of participants who achieve CR and PR through the study (approximately 4 years), as determined by the investigator according to the RECIST V1.1 for participants with solid tumors or Lugano classification for lymphoma.
Measure:Phase 2: Duration of Response (DOR)
Time Frame:From the time of documentation of tumor response to the first recorded occurrence of disease progression (PD) or death from any cause (whichever occurs first), through end of study (up to 4 years)
Safety Issue:
Description:DOR is the time from the date of first documentation of a PR or better to the date of first documentation of progressive disease for responders (PR or better) and will be determined by the investigator according to RECIST v1.1 for participants with solid tumors or Lugano classification for lymphoma.
Measure:Phase 2: Disease Control Rate (DCR)
Time Frame:From the first dose until best response is achieved (up to 4 years)
Safety Issue:
Description:DCR is defined as the percentage of participants who achieve stable disease (SD) or better (determined by the investigator according to RECIST v1.1 criteria for solid tumors or Lugano classification for lymphoma) greater than (>) 6 weeks during the study in the response-evaluable population.
Measure:Phase 2: Time to Response (TTR)
Time Frame:From the date of first study drug administration to the date of first documented PR or better (up to 4 years)
Safety Issue:
Description:TTR is defined as the time from the date of first study drug administration to the date of first documented PR or better by the investigator for responders according to RECIST v1.1 for participants with solid tumors or Lugano classification for lymphoma.
Measure:Phase 2: Time to Progression (TTP)
Time Frame:From the date of first study drug administration to the date of first documented PD (up to 4 years)
Safety Issue:
Description:TTP is defined as the time from the date of the first dose administration to the date of first documented progressive disease and will be determined by the investigator according to RECIST v1.1 for participants with solid tumors or Lugano classification for lymphoma.
Measure:Phase 2: Progression-free Survival (PFS)
Time Frame:From the date of the first dose administration to the date of first documentation of PD or death due to any cause whichever occurs first, through the end of the study (up to 4 years)
Safety Issue:
Description:PFS is defined as the time from the date of the first dose administration to the date of first documentation of progressive disease or death due to any cause, whichever occurs first and will be determined by the investigator according to RECIST v1.1 for participants with solid tumors or Lugano classification for lymphoma.
Measure:Phase 2: Overall Survival (OS)
Time Frame:From the date of first study drug administration to the date of death (up to 4 years)
Safety Issue:
Description:OS is defined as the time from the date of the first dose administration to the date of death.
Measure:Phase 2: Number of Participants With TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation and SUMO Pathway Inhibition in Skin/Blood
Time Frame:Up to 48 months
Safety Issue:
Description:
Measure:COVID-19 Expansion: Number of Participants Reporting one or More TEAEs
Time Frame:Up to 9 months
Safety Issue:
Description:
Measure:COVID-19 Expansion: Number of Participants Based on Severity of TEAEs
Time Frame:Up to 9 months
Safety Issue:
Description:Severity Grades will be evaluated as per National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE), version 5.0.
Measure:COVID-19 Expansion: Duration of TEAEs
Time Frame:Up to 9 months
Safety Issue:
Description:
Measure:COVID-19 Expansion: Change from Baseline in National Early Warning Score (NEWS)
Time Frame:Up to 9 months
Safety Issue:
Description:NEWS determines the degree of illness of participants and prompts critical care intervention. It will be based on the score allocated to respiratory rate, peripheral capillary oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate and level of consciousness.
Measure:COVID-19 Expansion: Percentage of Participants Reporting Each Hospitalization Severity Rating
Time Frame:Up to 9 months
Safety Issue:
Description:Percentage of participants will be reported based on severity rating on a 6-point ordinal scale, which will include: 1 (death); 2 (hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation, hospitalized); 3 (on non-invasive ventilation or high flow oxygen devices); 4 (hospitalized, requiring supplemental oxygen); 5 (hospitalized, not requiring supplemental oxygen); and 6 (not hospitalized).
Measure:COVID-19 Expansion: Change From Baseline in SARS-CoV-2 Viral Load in Nasopharyngeal or Oropharyngeal Samples
Time Frame:Up to 9 months
Safety Issue:
Description:Change from Baseline in SARS-CoV-2 viral Load in nasopharyngeal or oropharyngeal samples will be determined by viral response. The nasopharyngeal swab will be collected from both nostrils or from the same nostril every time.
Measure:COVID-19 Expansion: Percentage of Participants Requiring Oxygen Supplementation; Assisted or Positive Pressure Non-invasive Ventilation; and Invasive Ventilation, on Days 3, 5, 8, 11, 15, and 30
Time Frame:Days 3, 5, 8, 11, 15, and 30
Safety Issue:
Description:
Measure:COVID-19 Expansion: Percentage of Participants That met Intensive Care Unit (ICU) Criteria
Time Frame:Up to 9 months
Safety Issue:
Description:
Measure:COVID-19 Expansion: Duration of Hospitalization
Time Frame:Up to 9 months
Safety Issue:
Description:
Measure:COVID-19 Expansion: Time to Viral Ribonucleic Acid (RNA) Negativity in Nasopharyngeal or Oropharyngeal Samples
Time Frame:Up to 9 months
Safety Issue:
Description:Time from the first dose of TAK-981 to viral load negativity (below level of detection).
Measure:COVID-19 Expansion: Time to Discharge or to a NEWS of Less Than or Equal to (<=) 3 and Maintained for 24 Hours
Time Frame:Up to 9 months
Safety Issue:
Description:Time from first dose of TAK-981 to participant's discharge or to NEWS score <=3. NEWS determines the degree of illness of participants and prompts critical care intervention. It will be based on the score allocated to respiratory rate, peripheral capillary oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate and level of consciousness.
Measure:COVID-19 Expansion: Number of Deaths in Hospital due to any Cause in First 30 Days and in 90 Days
Time Frame:Days 30 and 90
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Millennium Pharmaceuticals, Inc.

Trial Keywords

  • Drug therapy

Last Updated

December 3, 2020