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 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 may make
multiple visits to the clinic and 30, 60, and 90 days after last dose of study drug for
follow-up assessments.

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.