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
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
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.
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
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
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)
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both