An Efficacy and Safety Study of JNJ-42756493 in Participants With Urothelial Cancer

This is a multicenter, open-label study (participants will know the identity of study drugs
administered) to evaluate the efficacy and safety of JNJ-42756493 in participants with
urothelial cancer. The study comprises a 30-days Screening Phase, a Treatment Phase comprised
of 28-day treatment cycles that will continue until disease progression or unacceptable
toxicity occurs, and a post-treatment Follow-up Phase that will extend from the
End-of-Treatment Visit until the participant has died, withdraws consent, is lost to
follow-up, or the end of the study, whichever comes first. The end of study is defined as
approximately 12 months after last participant is enrolled. Safety will be monitored
throughout the study.

Inclusion Criteria:

- Must have histologic demonstration of metastatic or surgically unresectable urothelial
cancer. Minor components of variant histology such as glandular or squamous
differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or
micropapillary change are acceptable

- Must have measurable disease according to the Response Evaluation Criteria in Solid
Tumors (RECIST, version 1.1) at baseline

- Must have an Eastern Cooperative Oncology Group (ECOG) performance status score 0, 1,
or 2

- Must have adequate bone marrow, liver, and renal function as described in protocol

- Negative pregnancy test (urine or serum beta human chorionic gonadotropin [b-hCG]) at
Screening for women of child bearing potential who are sexually active

- Must have shown disease progression according to RECIST, version 1.1, following prior
chemotherapy for metastatic or surgically unresectable urothelial cancer. Subjects who
received neoadjuvant or adjuvant chemotherapy and showed disease recurrence or
progression according to RECIST, version 1.1, within 12 months of the last dose are
considered to have received chemotherapy in the metastatic setting. These subjects
will be referred to as chemo-refractory subjects. (Subjects who have shown disease
progression according to RECIST, version 1.1 following prior treatment with
anti-Programmed death-ligand 1 (anti PDL1/PD1) antibodies are also eligible)

Exclusion Criteria:

- Received chemotherapy, targeted therapies, definitive radiotherapy, or treatment with
an investigational anticancer agent within 2 weeks (in the case of nitrosoureas and
mitomycin C, within 6 weeks; in the case of immunotherapy, within 4 weeks) before the
first administration of study drug. Localized palliative radiation therapy (but should
not include radiation to target lesions) and ongoing bisphosphonates and denosumab,
are permitted

- Has persistent phosphate level greater than upper limit of normal (ULN) during
screening (within 14 days of treatment and prior to Cycle 1 Day 1) and despite medical
management

- Has a history of or current uncontrolled cardiovascular disease

- Females who are pregnant, breast-feeding, or planning to become pregnant within 3
months after the last dose of study drug and males who plan to father a child while
enrolled in this study or within 5 months after the last dose of study drug

- Has not recovered from reversible toxicity of prior anticancer therapy (except
toxicities which are not clinically significant such as alopecia, skin discoloration,
or Grade 1 neuropathy)