Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of Investigational Treatments in Combination With Standard of Care Immune Checkpoint Inhibitors in Participants With Advanced Melanoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02723006
Recruitment Status : Terminated (Business decision: Protocol efficacy futility met)
First Posted : March 30, 2016
Results First Posted : April 1, 2021
Last Update Posted : April 1, 2021
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Tracking Information
First Submitted Date  ICMJE March 25, 2016
First Posted Date  ICMJE March 30, 2016
Results First Submitted Date  ICMJE May 1, 2019
Results First Posted Date  ICMJE April 1, 2021
Last Update Posted Date April 1, 2021
Actual Study Start Date  ICMJE June 22, 2016
Actual Primary Completion Date May 11, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 3, 2021)
Number of Dose Limiting Toxicities (DLTs) During the Dose-escalation Safety Lead-in Phase [ Time Frame: TAK-580 + Nivolumab and TAK-202 + Nivolumab: Baseline up to Week 9; Vedolizumab + Nivolumab + Ipilimumab: Baseline up to Week 7 ]
DLTs was evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
Original Primary Outcome Measures  ICMJE
 (submitted: March 25, 2016)
Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE's) [ Time Frame: Baseline up to 30 days after last dose of study drug (Week 53) ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 3, 2021)
  • Overall Response Rate (ORR) During the Dose-escalation Safety Lead-in Phase [ Time Frame: Baseline up to Week 50 ]
    ORR based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. was the percentage of participants with complete response (CR) or partial response (PR). CR: was disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to less than (<) 10 millimeter (mm). PR: was at least a 30 percent (%) decrease in sum of diameter (SOD) of target lesions, taking as reference the baseline SOD.
  • Duration of Response (DOR) During the Dose-escalation Safety Lead-in Phase [ Time Frame: From date of first documented confirmed CR/PR until date of first documentation of PD or death (up to Week 50) ]
    DOR based on RECIST version 1.1 was the time from the date of first documented confirmed CR/PR until the first documentation of confirmed progressive disease (PD) or death, whichever occurred first. CR: was disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to <10 mm. PR: at least 30% decrease in SOD of target lesions, taking as reference the baseline SOD persistence of one or more non- target lesions and/or maintenance of tumor marker level above the normal limits. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
  • Progression-free Survival (PFS) During the Dose-escalation Safety Lead-in Phase [ Time Frame: From first dose date to the date of the first documentation of confirmed PD or death (up to Week 50) ]
    PFS was the time from first dose date to date of the first documentation of confirmed PD or death, whichever occurred first. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions.
  • Overall Survival (OS) During the Dose-escalation Safety Lead-in Phase [ Time Frame: From first dose of study drug until date of death from any cause (up to Week 50) ]
    OS was the time from date of first dose of study drug until date of death from any cause.
  • Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: From the first dose of study drug up to 30 days after the last dose of study drug (up to Week 50) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 25, 2016)
  • Overall Response Rate (ORR) [ Time Frame: Baseline, Week 3, Week 9, Week 49 (End-of treatment) ]
  • Duration of Response (DOR) [ Time Frame: Baseline, Week 3, Week 9, Week 49 (End-of treatment) ]
  • Progression-free Survival (PFS) [ Time Frame: Baseline, Week 3, Week 9, Week 49 (End-of treatment) ]
  • Overall Survival (OS) [ Time Frame: Baseline up to 50 Weeks or death (which ever occurs first) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of Investigational Treatments in Combination With Standard of Care Immune Checkpoint Inhibitors in Participants With Advanced Melanoma
Official Title  ICMJE An Open-Label, Phase 1b, Multi-Arm Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of Investigational Treatments in Combination With Standard of Care Immune Checkpoint Inhibitors in Patients With Advanced Melanoma
Brief Summary The purpose of this study is to determine the initial safety profile and initial antitumor activity of the combination treatments (immune checkpoint inhibitors [nivolumab, ipilimumab] with investigational drugs [TAK-580, TAK-202 (plozalizumab), vedolizumab]) in the 3 arms when administered to participants with advanced melanoma.
Detailed Description

The drugs being tested in this study are called TAK-580, TAK-202 (plozalizumab), and vedolizumab. These investigational drugs were given along with standard of care checkpoint inhibitors ([nivolumab in Arms 1 and 2] or nivolumab + ipilimumab in Arm 3). This study looked at the safety profile of the combination treatments in each arm when administered to participants with metastatic melanoma.

The study planned to enroll approximately 156 participants. Participants were assigned to one of the 3 treatment groups:

  • TAK-580 + nivolumab
  • TAK-202 (plozalizumab) + nivolumab
  • vedolizumab + nivolumab + ipilimumab

This study consists of 3 parts. A dose-escalation safety lead-in phase, confirmatory safety phase and a cohort expansion phase. This multi-center trial will be conducted in the United States. The overall time to participate in this study is 50 weeks. Participants may make multiple visits to the clinic and 30, 60, and 90 days after last dose of study drug for follow-up assessments.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Melanoma
Intervention  ICMJE
  • Drug: TAK-580
    TAK-580 tablets
    Other Name: MLN2480
  • Drug: TAK-202
    TAK-202 infusion
    Other Names:
    • MLN1202
    • plozalizumab
  • Drug: vedolizumab
    vedolizumab infusion
    Other Name: Entyvio
  • Drug: nivolumab
    nivolumab infusion
    Other Name: Opdivo
  • Drug: ipilimumab
    ipilimumab infusion
    Other Name: Yervoy
Study Arms  ICMJE
  • Experimental: TAK-580 + nivolumab
    TAK-580 orally, once weekly along with nivolumab, intravenous, every 2 weeks.
    Interventions:
    • Drug: TAK-580
    • Drug: nivolumab
  • Experimental: TAK-202 (plozalizumab) + nivolumab
    TAK-202 (plozalizumab) 2 milligram (mg), intravenous, once in Week 1, 3, 5, 9, and every 4 weeks thereafter with nivolumab infusion, intravenous, every 2 weeks.
    Interventions:
    • Drug: TAK-202
    • Drug: nivolumab
  • Experimental: vedolizumab + nivolumab + ipilimumab
    Vedolizumab intravenous, once in Week 1, 3, 5, and 13 along with nivolumab infusion, intravenous, once in Week 1, 4, 7, 10, and 13 and every 2 weeks thereafter, along with ipilimumab intravenous, once in Week 1, 4, 7, and 10.
    Interventions:
    • Drug: vedolizumab
    • Drug: nivolumab
    • Drug: ipilimumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: May 22, 2018)
22
Original Estimated Enrollment  ICMJE
 (submitted: March 25, 2016)
156
Actual Study Completion Date  ICMJE May 11, 2018
Actual Primary Completion Date May 11, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Is a male or female participant of 18 years or older.
  2. Has histologically confirmed, unresectable Stage III or Stage IV melanoma per the American Joint Committee on Cancer (AJCC) staging system.
  3. Has an eastern cooperative oncology group (ECOG) performance status of 0-1.
  4. Adequate bone marrow reserve and renal and hepatic function within 28 days before the first dose of study drug on the basis of the defined laboratory parameters.
  5. For TAK-580 + nivolumab and TAK-202 (plozalizumab) + nivolumab only: Had disease accessible for repeat nonsignificant risk biopsy (those occurring outside the brain, lung/mediastinum, and pancreas, or obtained with endoscopic procedures extending beyond the esophagus, stomach, or bowel) and willingness to undergo serial tumor biopsies.
  6. Additional Inclusion Requirements for TAK-580 + nivolumab

    a) BRAF V600 mutation-positive or NRAS mutation-positive disease previously untreated with RAF, MEK, or other inhibitors of the mitogen-activated protein kinase (MAPK) pathway. Participants who have progressed on these agents can still be enrolled in TAK-202 (plozalizumab) + nivolumab or vedolizumab + nivolumab + ipilimumab.

  7. Additional Inclusion Requirements for expansion cohorts only a) Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (Version 1.1) and at least 1 nonsignificant risk, non-target lesion accessible for biopsy per the guidelines above (for TAK-580 + nivolumab and TAK-202 (plozalizumab) + nivolumab only).

Exclusion Criteria:

  1. Has active brain metastases or leptomeningeal metastases. Participants with brain metastases are eligible if these have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for at least 4 weeks after treatment is complete and within 28 days prior to first dose of study drug administration. There must also be no requirement for high doses of systemic corticosteroids that could result in immunosuppression (greater than [>] 10 milligram per day [mg/day] prednisone equivalents) for at least 2 weeks prior to study drug administration.
  2. Completed a prior therapy less than (<) 2 weeks prior to first dose and for whom adverse events (AEs) related to prior therapy had not returned to baseline or improved to Grade 1.
  3. Has active, known or suspected autoimmune disease.
  4. Has a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of study drug administration.
  5. Has a history of pneumonitis requiring treatment with steroids; history of idiopathic pulmonary fibrosis (including pneumonitis), interstitial lung disease, drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest computed tomography (CT) scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  6. Is previously diagnosed human immunodeficiency virus (HIV) infection or active hepatitis B or C.
  7. Additional Exclusion Requirements for arm 1 only (nivolumab Plus TAK-580)

    1. Concomitant use or administration of clinically significant enzyme inducers less than or equal to (<=) 14 days before the first dose of TAK-580.
    2. Treatment with gemfibrozil (or other strong CYP2C8 inhibitor) within 14 days before the first dose of TAK-580.
    3. Left ventricular ejection fraction (LVEF) <50 percent (%) as measured by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA) within 4 weeks before receiving the first dose of study drug.
    4. Known gastrointestinal (GI) disease or prior GI procedure that could interfere with the oral absorption or tolerance of the TAK-580.
  8. Additional Exclusion Requirements for arm 3 only (vedolizumab Plus nivolumab Plus ipilimumab)

    1. Had prior exposure to rituximab, natalizumab, vedolizumab, or alemtuzumab.
    2. Has a history of any major neurological disorders, including stroke, multiple sclerosis, or neurodegenerative disease.
    3. Has taken any live vaccinations within 30 days before study drug administration except for the influenza vaccine.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02723006
Other Study ID Numbers  ICMJE C28003
U1111-1177-4142 ( Other Identifier: WHO )
2015-005554-35 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach 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.
Responsible Party Takeda ( Millennium Pharmaceuticals, Inc. )
Study Sponsor  ICMJE Millennium Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
PRS Account Takeda
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP