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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

NCT02723006

Description:

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.

Related Conditions:
  • Melanoma
Recruiting Status:

Terminated

Phase:

Phase 1

Trial Eligibility

Document

Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of Investigational Treatments in Combination With Standard of Care Immune Checkpoint Inhibitors in Participants With Advanced <span class="go-doc-concept go-doc-disease">Melanoma</span>

Title

  • Brief Title: 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: 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
  • Clinical Trial IDs

    NCT ID: NCT02723006

    ORG ID: C28003

    NCI ID: U1111-1177-4142

    Trial Conditions

    Melanoma

    Trial Interventions

    Drug Synonyms Arms
    TAK-580 MLN2480 TAK-580 + nivolumab
    TAK-202 MLN1202, plozalizumab TAK-202 (plozalizumab) + nivolumab
    Vedolizumab Entyvio vedolizumab + nivolumab + ipilimumab
    nivolumab Opdivo TAK-580 + nivolumab, TAK-202 (plozalizumab) + nivolumab, vedolizumab + nivolumab + ipilimumab
    ipilimumab Yervoy vedolizumab + nivolumab + ipilimumab

    Trial Purpose

    The purpose of this study is to determine the initial safety profile 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 will
    look at the safety profile of the combination treatments in each arm when administered to
    participants with advanced melanoma.

    The study will enroll approximately 156 participants. Participants will be 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 will make
    multiple visits to the clinic and 30 days after last dose of study drug for a follow-up
    assessment.

    Trial Arms

    Name Type Description Interventions
    TAK-580 + nivolumab Experimental TAK-580 orally, once weekly along with nivolumab, intravenous, twice weekly. TAK-580, nivolumab
    TAK-202 (plozalizumab) + nivolumab Experimental TAK-202 (plozalizumab) 2 mg, intravenous, once in Week 1, 3, 5, 9, and every 4 weeks thereafter with nivolumab infusion, intravenous, twice weekly. TAK-202, nivolumab
    vedolizumab + nivolumab + ipilimumab Experimental Vedolizumab intravenous, once in Week 1, 3, 5, and 13 along with nivolumab infusion, intravenous, once in Week 3, 6, 9, and 12 and every 2 weeks thereafter, along with ipilimumab intravenous, once in Week 3, 6, 9, and 12. Vedolizumab, nivolumab, ipilimumab

    Eligibility Criteria

    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. Had disease accessible for repeat biopsy and willingness to undergo serial tumor
    biopsies.

    6. Additional Inclusion Requirements for arm 1 only (nivolumab + TAK-580)

    a) BRAF (gene) V600 mutation-positive or NRAS (gene) 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 Arms 2 or 3.

    7. Additional Inclusion Requirements for expansion cohorts only a) Measurable disease
    per RECIST guidelines (v 1.1) and at least 1 non-target lesion accessible for biopsy
    per the guidelines above.

    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 mg/day prednisone equivalents) for
    at least 2 weeks prior to study drug administration.

    2. Has ocular melanoma.

    3. Had prior treatment with an anti-programmed cell death 1 (PD-1) , anti-PD-L1 (ligands
    for PD-1), anti-PD-L2 (ligands for PD-1).

    4. Has active, known or suspected autoimmune disease.

    5. Has a condition requiring systemic treatment with either corticosteroids or other
    immunosuppressive medications within 14 days of study drug administration.

    6. 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 CT scan; history of radiation pneumonitis in the radiation field (fibrosis) is
    permitted.

    7. Is previously diagnosed HIV infection or active hepatitis B or C.

    8. Additional Exclusion Requirements for arm 1 only (nivolumab Plus TAK-580)

    1. Concomitant use or administration of clinically significant enzyme inducers less
    than 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) less than (<)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 GI disease or prior GI procedure that could interfere with the oral
    absorption or tolerance of the TAK-580.

    9. 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, brain tumor, or neurodegenerative disease.

    3. Has taken any live vaccinations within 30 days before study drug administration
    except for the influenza vaccine.

    4. Has previous anti- cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4)
    therapies.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE's)

    Secondary Outcome Measures

    Overall Response Rate (ORR)

    Duration of Response (DOR)

    Progression-free Survival (PFS)

    Overall Survival (OS)

    Trial Keywords

    Drug Therapy