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A Study of TAK-676 and TAK-676 in Combination With Pembrolizumab in Adults With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT04420884
Recruitment Status : Recruiting
First Posted : June 9, 2020
Last Update Posted : May 7, 2021
Sponsor:
Information provided by (Responsible Party):
Takeda

Brief Summary:

It is hoped that TAK-676, when given on its own or given with pembrolizumab will eventually help people with advanced or metastatic solid tumors.

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 side effects from it.

At the first visit, the study doctor will check who can take part. Participants will receive TAK-676 slowly through a vein (infusion). This will happen on 3 different days during a 21-day cycle. Different small groups of participants will receive lower to higher doses of TAK-676. Some participants will receive TAK-676 by itself and others will receive TAK-676 with pembrolizumab.

Participants will stay in the clinic or hospital for 24 hours after each infusion of TAK-676 in the first cycle of treatment. Sometimes the study doctor will carry out a physical exam before the participant goes home. Participants will be given an emergency card to carry with them at all times. The card has information about the study including contact details and a 24-hour emergency number.

Some participants, who receive TAK-676 and are willing and able, will be asked to wear a removable patch on their chest to record vital signs for 21 days in the first cycle of treatment. Also, in the first cycle of treatment, participants will record their oral temperatures twice a day for 21 days in a diary when they go home after each infusion.

Throughout treatment, the clinic will regularly telephone the participants to check on their health.


Condition or disease Intervention/treatment Phase
Solid Neoplasms Drug: TAK-676 Drug: Pembrolizumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 76 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 22, 2020
Estimated Primary Completion Date : March 11, 2023
Estimated Study Completion Date : March 11, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Monotherapy Dose Escalation Phase: TAK-676 SA

Safety Lead-in: TAK-676 0.1 milligram (mg), infusion, intravenously, once weekly, on Days 1, 8 and 15 in 21-day treatment Cycles.

TAK-676 SA Dose Escalation: TAK-676 SA, infusion, intravenously, 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 Phase.

Drug: TAK-676
TAK-676 intravenous Infusion.

Experimental: Combination Dose Escalation Phase: TAK-676 + Pembrolizumab

TAK-676, infusion, intravenously, once weekly on Days 1, 8 and 15 in each 21-day treatment cycles with escalating doses (0.2 mg and above) plus pembrolizumab 200 mg, infusion, intravenously, once on Day 1 in each 21-day treatment cycles.

The dosing will be initiated based on the available safety and tolerability data from the initial TAK-676 SA cohorts.

Drug: TAK-676
TAK-676 intravenous Infusion.

Drug: Pembrolizumab
Pembrolizumab intravenous Infusion.




Primary Outcome Measures :
  1. Number of Participants Reporting one or More Treatment-emergent Adverse Events (TEAEs) and Based on TEAEs Severity [ Time Frame: Up to 30 months ]
    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).

  2. Number of Participants with Dose-Limiting Toxicities (DLTs) [ Time Frame: Up to 30 months ]
    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.

  3. Number of Participants Reporting One or More Treatment Emergent Serious Adverse Event (SAEs) [ Time Frame: Up to 30 months ]
  4. Number of Participants With one or More TEAEs Leading to Dose Modifications and Treatment Discontinuations [ Time Frame: Up to 30 months ]

Secondary Outcome Measures :
  1. Cmax: Maximum Observed Plasma Concentration for TAK-676 [ Time Frame: Cycle 1 Days 1 and 8: pre-infusion and at multiple time points (up to 24 hours) post-infusion (Cycle length=21 days) ] ]
  2. Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-676 [ Time Frame: Cycle 1 Days 1 and 8: pre-infusion and at multiple time points (up to 24 hours) post-infusion (Cycle length=21 days) ] ]
  3. AUCt: Area under the Concentration-time Curve From Time 0 to Time t for TAK-676 [ Time Frame: Cycle 1 Days 1 and 8: pre-infusion and at multiple time points (up to 24 hours) post-infusion (Cycle length=21 days) ] ]
  4. AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity for TAK-676 [ Time Frame: Cycle 1 Days 1 and 8: pre-infusion and at multiple time points (up to 24 hours) post-infusion (Cycle length=21 days) ] ]
  5. t1/2: Terminal Disposition Phase Half-life for TAK-676 [ Time Frame: Cycle 1 Days 1 and 8: pre-infusion and at multiple time points (up to 24 hours) post-infusion (Cycle length=21 days) ] ]
  6. CL: Total Clearance After Intravenous Administration for TAK-676 [ Time Frame: Cycle 1 Days 1 and 8: pre-infusion and at multiple time points (up to 24 hours) post-infusion (Cycle length=21 days) ] ]
  7. Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-676 [ Time Frame: Cycle 1 Days 1 and 8: pre-infusion and at multiple time points (up to 24 hours) post-infusion (Cycle length=21 days) ] ]
  8. CLR: Renal Clearance for TAK-676 [ Time Frame: Cycle 1 Day 1: start of infusion and at multiple time points (up to 24 hours) after end of infusion (Cycle length=21 days) ]
  9. Percentage of Dose Excreted in Urine During 24 Hours After Dosing [ Time Frame: Cycle 1 Day 1: start of infusion and at multiple time points (up to 24 hours) after end of infusion (Cycle length=21 days) ]
  10. CLR/CL%: Renal Clearance as Percentage of Total Clearance for TAK-676 [ Time Frame: Cycle 1 Day 1: start of infusion and at multiple time points (up to 24 hours) after end of infusion (Cycle length=21 days) ]
  11. Overall Response Rate (ORR) [ Time Frame: Up to 30 months ]
    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.

  12. Disease Control Rate (DCR) [ Time Frame: Up to 30 months ]
    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.

  13. Duration of Response (DOR) [ Time Frame: Up to 30 months ]
    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.

  14. Time to Response (TTR) [ Time Frame: Up to 30 months ]
    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.

  15. Number of Participants with Upregulation of TAK-676-Induced Stimulator of Interferon Genes (STING) [ Time Frame: Up to 30 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 to 1.
  2. Life expectancy >12 weeks, as assessed by the investigator.
  3. TAK-676 SA:

    o With histologically confirmed (cytological diagnosis is acceptable) advanced or metastatic solid tumors that have no standard therapeutic options or are intolerant to these therapies.

  4. TAK-676 in combination with pembrolizumab:

    o With histologically confirmed (cytological diagnosis is acceptable) advanced or metastatic solid tumors that have no standard therapeutic options or are intolerant to them, including:

    • Tumors that have relapsed or are refractory to anti-programmed cell death protein 1 (anti-PD-1)/anti-programmed cell death ligand 1 (anti-PD-L1) therapy.
    • Tumors that are naive to anti-PD-1/ anti-PD-L1 therapy.
  5. Adequate bone marrow, renal, hepatic and cardiac functions.
  6. Left ventricular ejection fraction (LVEF) >50%, as measured by echocardiogram or multiple-gated acquisition (MUGA) scan within 4 weeks before receiving the first dose of study drug.
  7. Clinically significant toxic effects of previous therapy have recovered to Grade 1 (per NCI CTCAE Version 5.0) or baseline, except for alopecia, Grade 2 peripheral neuropathy, and/or autoimmune endocrinopathies with stable endocrine replacement therapy.
  8. Once peripheral evidence of TAK-676 pharmacodynamic stimulation of the innate and/or adaptive immune system is observed in the blood and/or clinical response/partial response (CR/PR) is observed in at least 1 participant, subsequent participants must:

    • Have at least 1 lesion amenable for biopsy.
    • Agree to have 2 tumor biopsies: 1 during the screening period and 1 while on TAK-676 treatment.
  9. Must have at least 1 RECIST v.1.1-evaluable (measurable or nonmeasurable) lesion.
  10. Pharmacokinetic (PK)/pharmacodynamic blood must be drawn on a peripherally-inserted catheter. TAK-676 is preferentially administered through a central line, but peripheral infusion is acceptable. If a peripheral line is used for TAK-676 and/or pembrolizumab infusion, it must be separate than the one used for PK/ pharmacodynamic collection.

Exclusion Criteria:

  1. Corrected QT interval by Fredericia (QTcF) greater than (>) 450 milliseconds (men) or >475 milliseconds (women) on a 12-lead ECG during the screening period.
  2. Grade greater than or equal to (>=) 2 hypotension (that is, hypotension for which nonurgent intervention is required) at screening or during C1D1 predose assessment.
  3. Oxygen saturation less than (<) 92 percent (%) on room air at screening or during C1D1 predose assessment.
  4. Treated with other STING agonists/antagonist and toll-like receptors agonists within the past 6 months.
  5. Active vaping within 90 days of C1D1 of study drug(s).
  6. Active smoking.
  7. Current history of pneumonitis, interstitial lung disease, severe chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, other restrictive lung diseases, acute pulmonary embolism, or Grade >=2 pleural effusion or ascites not controlled by tap or requiring indwelling catheters.
  8. History of brain metastasis unless:

    • Clinically stable (that is, >=6 weeks) following prior surgery, whole-brain radiation, or stereotactic radiosurgery, AND
    • Off corticosteroids.
  9. Ongoing Grade >= 2 infection or participants with Grade >=2 fever of malignant origin.
  10. Chronic, active hepatitis (example: participants with known hepatitis B surface antigen seropositive and/or detectable hepatitis C virus [HCV]-RNA).
  11. For participants in the SA arm only: refusal of standard therapeutic options.
  12. For participants in the combination arm only: contraindication and/or intolerance to the administration of pembrolizumab.
  13. Concurrent chemotherapy, immunotherapy (except for pembrolizumab in the combination arm), biologic, or hormonal therapy (except for adjuvant endocrine therapy for a history of breast cancer). Concurrent use of hormones for noncancer-related conditions is acceptable (except for corticosteroid hormones).
  14. Radiation therapy within 14 days (42 days for radiation to the lungs) and/or systemic treatment with radionuclides within 42 days before C1D1 of study drug(s). Participants with clinically relevant ongoing pulmonary complications from prior radiation therapy are not eligible.
  15. Use of systemic corticosteroids or other immunosuppressive therapy, concurrently or within days of C1D1 of study drug(s), with the following exceptions:

    • Topical, intranasal, inhaled, ocular, and/or intra-articular corticosteroids.
    • Physiological doses of replacement steroid therapy (example: for adrenal insufficiency).
  16. Use of medications that are known clinical OATP1B1 and/or OATP1B3 inhibitors, concurrently or within 14 days of C1D1 of study drug(s).
  17. Receipt of live attenuated vaccine within 28 days of C1D1 of study drug(s).
  18. Recipients of allogeneic or autologous stem cell transplantation or organ transplantation.

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): NCT04420884


Contacts
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Contact: Takeda Contact +1-877-825-3327 medinfoUS@takeda.com

Locations
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United States, California
University of California San Diego Moores Cancer Center Recruiting
La Jolla, California, United States, 92093
Contact: Site Contact    858-657-7000    spatel@ucsd.edu   
Principal Investigator: Sandip Patel         
United States, Colorado
Sarah Cannon Research Institute- HealthOne, Denver Recruiting
Denver, Colorado, United States, 80218
Contact: Site Contact    720-754-2610    gerald.falchook@scresearch.net   
Principal Investigator: Gerald Falchook         
United States, Connecticut
Yale Cancer Center Recruiting
New Haven, Connecticut, United States, 06520
Contact: Site Contact    203-785-3333    patricia.lorusso@yale.edu   
Principal Investigator: Patricia LoRusso         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02109
Contact: Site Contact    617-724-4000    xgao4@partners.org   
Principal Investigator: Xin Gao         
United States, Oregon
Providence Portland Medical Center Recruiting
Portland, Oregon, United States, 97213
Contact: Site Contact    503-215-5696    rachel.sanborn@providence.org   
Principal Investigator: Rachel Sanborn         
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: Site Contact    215-214-1676    anthony.olszanski@fccc.edu   
Principal Investigator: Anthony Olszanski         
University of Pittsburgh Medical Center - Hillman Cancer Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Site Contact    773-702-6180    lukejj@upmc.edu   
Principal Investigator: Jason Luke         
United States, Texas
Mary Crowley Cancer Research Recruiting
Dallas, Texas, United States, 75230
Contact: Site Contact    972-566-3000 ext 4    jstrauss@marycrowley.org   
Principal Investigator: James Strauss         
Canada, Ontario
Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Site Contact    416-946-4534    philippe.bedard@uhn.ca   
Principal Investigator: Phillippe Bedard         
Sponsors and Collaborators
Takeda
Investigators
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Study Director: Study Director Takeda
Additional Information:
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Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT04420884    
Other Study ID Numbers: TAK-676-1002
U1111-1241-4427 ( Registry Identifier: WHO )
First Posted: June 9, 2020    Key Record Dates
Last Update Posted: May 7, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan 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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
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.
URL: https://vivli.org/ourmember/takeda/

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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:
Drug Therapy
Additional relevant MeSH terms:
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Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents