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

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ClinicalTrials.gov Identifier: NCT04157517
Recruitment Status : Not yet recruiting
First Posted : November 8, 2019
Last Update Posted : November 27, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

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

Condition or disease Intervention/treatment Phase
Solid Neoplasms Carcinoma, Non-Small-Cell Lung Prostatic Neoplasms Drug: TAK-573 Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 105 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Other
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
Estimated Study Start Date : December 13, 2019
Estimated Primary Completion Date : January 31, 2023
Estimated Study Completion Date : January 31, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Dose Escalation Phase: TAK-573 0.1 to 6 mg/kg
TAK-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.
Drug: TAK-573
TAK-573 intravenous infusion.

Experimental: Dose Expansion Phase: Metastatic or Locally Advanced NSCLC
TAK 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.
Drug: TAK-573
TAK-573 intravenous infusion.

Experimental: Dose Expansion Phase: CRPC
TAK 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.
Drug: TAK-573
TAK-573 intravenous infusion.

Experimental: Dose Expansion Phase: Other (Not NSCLC or CRPC)
TAK 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.
Drug: TAK-573
TAK-573 intravenous infusion.




Primary Outcome Measures :
  1. Number of Participants Reporting one or More Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Up to 43 months ]
  2. Number of Participants with Grade 3 or Higher TEAEs [ Time Frame: Up to 43 months ]
    TEAEs Grades will be evaluated as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0.

  3. Number of Participants with Dose Limiting Toxicities (DLTs) [ Time Frame: Cycle 1 (Cycle length is equal to [=] 21 days) ]
    DLT will be defined as any of the TEAEs that occur during Cycle 1 and are considered by the investigator to be at least possibly related to TAK-573. Toxicity will be evaluated according to NCI CTCAE version 5.0.

  4. Number of Participants Reporting one or More Serious Adverse Event (SAEs) [ Time Frame: Up to 43 months ]
  5. Number of Participants with one or More TEAEs Leading to Dose Modifications and Treatment Discontinuations [ Time Frame: Up to 43 months ]

Secondary Outcome Measures :
  1. 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) ]
  2. 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) ]
  3. 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) ]
  4. 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) ]
  5. 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) ]
  6. 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) ]
  7. 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) ]
  8. Overall Response Rate (ORR) [ Time Frame: Up to 43 months ]
    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.

  9. Progression Free Survival (PFS) [ Time Frame: Up to 43 months ]
    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.

  10. Overall Survival (OS) [ Time Frame: Up to 43 months ]
    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.

  11. Disease Control Rate (DCR) [ Time Frame: Up to 43 months ]
    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.

  12. Duration of Response (DOR) [ Time Frame: Up to 43 months ]
    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.

  13. Number of Participants with TAK-573 Induced Type I Interferons (IFN) Gene Expression Signature in the Peripheral Blood [ Time Frame: Up to 43 months ]
  14. Cellular CD38 Receptor Occupancy (RO) of Peripheral Blood [ Time Frame: Up to 43 months ]
    Flow cytometric analysis will be done to determine CD38 RO of peripheral immune cells.

  15. Incidence and Titer of Anti-TAK-573 Antibodies [ Time Frame: Up to 43 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04157517


Contacts
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Contact: Takeda Study Registration Call Center +1-866-835-2233 globaloncologymedinfo@takeda.com

Locations
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United States, North Carolina
Levine Cancer Institute Not yet recruiting
Charlotte, North Carolina, United States, 28204
United States, Tennessee
Sarah Cannon Research Institute Not yet recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
Mary Crowley Cancer Research Not yet recruiting
Dallas, Texas, United States, 75230
NEXT Oncology Not yet recruiting
San Antonio, Texas, United States, 78240
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
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Study Director: Medical Director Millennium Pharmaceuticals, Inc.

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Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT04157517     History of Changes
Other Study ID Numbers: TAK-573-1001
U1111-1238-9163 ( Registry Identifier: WHO )
First Posted: November 8, 2019    Key Record Dates
Last Update Posted: November 27, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Takeda ( Millennium Pharmaceuticals, Inc. ):
Drug Therapy
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Prostatic Neoplasms
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Genital Neoplasms, Male
Urogenital Neoplasms
Genital Diseases, Male
Prostatic Diseases