Clinical Trials /

A Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics Study

NCT04157517

Description:

The purpose of this study is to determine the safety and tolerability of TAK-573 in participants with locally advanced or metastatic solid tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics Study
  • Official Title: An Open-Label, Dose-Escalation Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of TAK-573 in Adult Patients With Metastatic Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: TAK-573-1001
  • SECONDARY ID: U1111-1238-9163
  • NCT ID: NCT04157517

Conditions

  • Solid Neoplasms
  • Carcinoma, Non-Small-Cell Lung
  • Prostatic Neoplasms

Interventions

DrugSynonymsArms
TAK-573Dose Escalation Phase: TAK-573 0.1 to 6 mg/kg

Purpose

The purpose of this study is to determine the safety and tolerability of TAK-573 in participants with locally advanced or metastatic solid tumors.

Detailed Description

      The drug being tested in this study is called TAK-573. TAK-573 is being tested to evaluate
      the safety, tolerability, PK, and pharmacodynamics in participants with locally advanced or
      metastatic solid tumors. The study will include a dose escalation phase and a dose expansion
      phase.

      The study will enroll approximately 105 participants (approximately 30 participants in dose
      escalation phase and approximately 75 participants in dose expansion phase).

      The dose escalation phase will enroll participants with solid tumors. The dose escalation
      phase is to evaluate single agent recommended phase 2 dose (RP2D) which could be either MTD
      or PAD.

      The dose expansion phase will be initiated once the MTD and /or PAD are determined for
      TAK-573. The dose expansion phase will enroll participants in 3 cohorts for participants with
      NSCLC, CRPC, or with other (not NSCLC or CRPC) advanced or metastatic solid tumors previously
      treated with an immune checkpoint inhibitor (CPI).

      This multi-center trial will be conducted in the United States. Participants with
      demonstrated clinical benefit may continue treatment beyond 1 year if approved by the
      sponsor. The overall time to participate in this study is 43 months. All participants will
      make an end of treatment (EOT) visit 30 days after receiving their last dose of study drug or
      before the start of subsequent systemic anticancer therapy, whichever occurs first for a
      safety follow up assessment.
    

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation Phase: TAK-573 0.1 to 6 mg/kgExperimentalTAK-573 0.1 to 6 milligram per kilogram (mg/kg), infusion, intravenously, once on Day 1 of each 21-days treatment cycle for up to 1 year. Administration of TAK-573 on Day 1 of each 28-days treatment cycle may also be evaluated.
  • TAK-573
Dose Expansion Phase: Metastatic or Locally Advanced NSCLCExperimentalTAK 573, infusion, intravenously, once on Day 1 of 21-days treatment cycle for up to 1 year in participants with metastatic or locally advanced non-small cell lung cancer (NSCLC). The dose of TAK-573 for dose expansion phase will be the maximum tolerated dose (MTD) and/or pharmacologically active dose (PAD) determined in the previous dose escalation phase.
  • TAK-573
Dose Expansion Phase: CRPCExperimentalTAK 573, infusion, intravenously, once on Day 1 of 21-days treatment cycle for up to 1 year in participants with CRPC. The dose of TAK-573 for dose expansion phase will be the MTD and/or PAD determined in the previous dose escalation phase.
  • TAK-573
Dose Expansion Phase: Other (Not NSCLC or CRPC)ExperimentalTAK 573, infusion, intravenously, once on Day 1 of 21-days treatment cycle for up to 1 year in other (not NSCLC or CRPC) participants. The dose of TAK-573 for dose expansion phase will be the MTD and/or PAD determined in the previous dose escalation phase.
  • TAK-573

Eligibility Criteria

        Inclusion Criteria:

          1. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

          2. For both the dose escalation and expansion cohort phases of the study, eligible
             participants must have histologically confirmed advanced (locoregionally recurrent,
             not amenable to curative therapy) or metastatic solid tumors who have no standard
             therapeutic option, are intolerant to these therapies, or have refused them.

             For the expansion cohort phase of the study, eligible participants must also have one
             of the following:

               -  NSCLC.

               -  CRPC.

               -  Other solid tumors that have progressed after previous treatment containing a
                  CPI.

          3. Measurable disease per mRECIST v.1.1. At least one target lesion amenable for biopsy
             is required for enrollment in the dose escalation phase, and 2 target lesions are
             required for enrollment in the dose expansion phase (one for biopsy and at least one
             for response assessment).

          4. Must agree to have a new (fresh) tumor biopsy during the screening period and on C2D2.

        Participants with CRPC without visceral disease are excluded from this requirement.

        Exclusion Criteria:

          1. Baseline QT interval with Fridericia's correction (QTcF) greater than (>) 480
             millisecond (msec) (Grade greater than or equal to [>=] 2), history of congenital long
             QT syndrome, or torsades de pointes.

          2. Ongoing or active infection.

          3. Autoimmune disease requiring systemic immunosuppressive therapy. The following are
             exceptions to this criterion: vitiligo, alopecia, endocrine insufficiency on stable on
             hormone replacement, psoriasis, or eczema not requiring systemic treatment.

          4. History of any of the following less than or equal to (<=) 6 months before first dose:
             New York Heart Association (NYHA) Grade III or IV congestive heart failure, unstable
             angina, myocardial infarction, unstable symptomatic ischemic heart disease, any
             ongoing symptomatic cardiac arrhythmias of Grade >2, pulmonary embolism, or
             symptomatic cerebrovascular events, or any other serious cardiac condition (example,
             symptomatic pericardial effusion or restrictive cardiomyopathy). Chronic, stable
             atrial fibrillation on stable anticoagulant therapy, including low molecular-weight
             heparin, is allowed.

          5. Known history of human immunodeficiency virus (HIV) infection or any other relevant
             congenital or acquired immunodeficiency. Testing during screening period is required
             only if indicated by specific local regulations or investigator's criteria.

          6. Known hepatitis B virus (HBV) surface antigen seropositive or detectable hepatitis C
             infection viral load. Testing during screening period is required only if indicated by
             local regulations or investigator's criteria.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants Reporting one or More Treatment-emergent Adverse Events (TEAEs)
Time Frame:Up to 43 months
Safety Issue:
Description:TEAEs Grades will be evaluated as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0.

Secondary Outcome Measures

Measure:Cmax: Maximum Observed Serum Concentration for TAK-573
Time Frame:Escalation: Cycles(C) 1-2 Day(D) 1: predose, at multiple timepoints (up to 72 hours [h]) postdose, C3-6 D1: predose and at multiple timepoints (up to 2h)postdose; Expansion: C1-6 D1: predose and at multiple timepoints (up to 4h) postdose (Cycle=21 days)
Safety Issue:
Description:
Measure:Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for TAK-573
Time Frame:Escalation: C1-2 D1: pre-dose and at multiple time points (up to 72 h) post-dose, C3-6 D1: pre-dose and at multiple time points (up to 2 h) post-dose; Expansion: C1-6 D1: pre-dose and at multiple time points (up to 4 h) post-dose (Cycle=21 days)
Safety Issue:
Description:
Measure:AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-573
Time Frame:Escalation: C1-2 D1: pre-dose and at multiple time points (up to 72 h) post-dose, C3-6 D1: pre-dose and at multiple time points (up to 2 h) post-dose; Expansion: C1-6 D1: pre-dose and at multiple time points (up to 4 h) post-dose (Cycle=21 days)
Safety Issue:
Description:
Measure:AUCinf: Area Under the Serum Concentration-time Curve From Time 0 to Infinity for TAK-573
Time Frame:Escalation: C1-2 D1: pre-dose and at multiple time points (up to 72 h) post-dose, C3-6 D1: pre-dose and at multiple time points (up to 2 h) post-dose; Expansion: C1-6 D1: pre-dose and at multiple time points (up to 4 h) post-dose (Cycle=21 days)
Safety Issue:
Description:
Measure:t1/2z: Terminal Disposition Phase Half-life for TAK-573
Time Frame:Escalation: C1-2 D1: pre-dose and at multiple time points (up to 72 h) post-dose, C3-6 D1: pre-dose and at multiple time points (up to 2 h) post-dose; Expansion: C1-6 D1: pre-dose and at multiple time points (up to 4 h) post-dose (Cycle=21 days)
Safety Issue:
Description:
Measure:CL: Total Clearance After Intravenous Administration for TAK-573
Time Frame:Escalation: C1-2 D1: pre-dose and at multiple time points (up to 72 h) post-dose, C3-6 D1: pre-dose and at multiple time points (up to 2 h) post-dose; Expansion: C1-6 D1: pre-dose and at multiple time points (up to 4 h) post-dose (Cycle=21 days)
Safety Issue:
Description:
Measure:Vss: Volume of Distribution at Steady State for TAK-573
Time Frame:Escalation: C1-2 D1: pre-dose and at multiple time points (up to 72 h) post-dose, C3-6 D1: pre-dose and at multiple time points (up to 2 h) post-dose; Expansion: C1-6 D1: pre-dose and at multiple time points (up to 4 h) post-dose (Cycle=21 days)
Safety Issue:
Description:
Measure:Overall Response Rate (ORR)
Time Frame:Up to 43 months
Safety Issue:
Description:ORR is defined as the percentage of participants who achieve complete response (CR) or partial response (PR) during the study in response-evaluable population. ORR will be assessed as per modified Response Evaluation Criteria in Solid Tumor (mRECIST) version 1.1 in participants with solid tumors and according to prostate cancer working group 3 (PCWG3) criteria for castrate-resistant prostate cancer (CRPC) participants.
Measure:Progression Free Survival (PFS)
Time Frame:Up to 43 months
Safety Issue:
Description:PFS is defined as the time from the date of the first dose of study drug to the date of first documentation of progressive disease according to mRECIST v.1.1 in participants with solid tumors and according to PCWG3 criteria for CRPC participants, or death due to any cause, whichever occurs first. Participants without documentation of progressive disease (PD) or death will be censored at the date of the last response assessment that is stable disease (SD) or better.
Measure:Overall Survival (OS)
Time Frame:Up to 43 months
Safety Issue:
Description:OS is defined as the time from the date of first dose of study drug to the date of death due to any cause. Participants without documentation of death at the time of analysis will be censored at the date last known to be alive. OS will be assessed as per mRECIST v1.1.
Measure:Disease Control Rate (DCR)
Time Frame:Up to 43 months
Safety Issue:
Description:DCR is defined as the percentage of participants who achieve CR, PR, or SD of at least 6 weeks (determined by the investigator) during the study in response-evaluable population. The DCR will be assessed as per mRECIST v1.1.
Measure:Duration of Response (DOR)
Time Frame:Up to 43 months
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 PD for responders (PR or better). Responders without documentation of PD will be censored at the date of last response assessment that is SD or better. DOR will be assessed as per mRECIST v1.1.
Measure:Number of Participants with TAK-573 Induced Type I Interferons (IFN) Gene Expression Signature in the Peripheral Blood
Time Frame:Up to 43 months
Safety Issue:
Description:
Measure:Cellular CD38 Receptor Occupancy (RO) of Peripheral Blood
Time Frame:Up to 43 months
Safety Issue:
Description:Flow cytometric analysis will be done to determine CD38 RO of peripheral immune cells.
Measure:Incidence and Titer of Anti-TAK-573 Antibodies
Time Frame:Up to 43 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Millennium Pharmaceuticals, Inc.

Trial Keywords

  • Drug Therapy

Last Updated

November 26, 2019