Glembatumumab Vedotin in Treating Patients With Metastatic or Locally Recurrent Uveal Melanoma

PRIMARY OBJECTIVES:

I. To characterize the clinical anti-tumor activity of CDX-011 (glembatumumab vedotin) as a
single-agent in the treatment of patients with metastatic uveal melanoma.

SECONDARY OBJECTIVES:

I. Description of the clinical safety and benefit of CDX-011 (glembatumumab vedotin) and
pharmacodynamics changes in glycoprotein NMB (glycoprotein [transmembrane] NMB) (GPNMB)
expression.

TERTIARY OBJECTIVES:

I. Characterization of the anti-tumor immunophenotype of patients receiving treatment.

II. Post hoc, correlation of rash with clinical benefit, or lack of rash with lack of
benefit, will also be explored.

OUTLINE:

Patients receive glembatumumab vedotin intravenously (IV) over 90 minutes every 3 weeks in
the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Inclusion Criteria:

- Patients must have histologically or cytologically confirmed metastatic or locally
recurrent uveal melanoma; because histologic or cytologic confirmation of primary
uveal melanoma is not always possible, confirmation of the clinical diagnosis of uveal
melanoma by the treating investigator is allowed; clinical diagnosis of uveal melanoma
is often made by an ophthalmologist, not by tissue diagnosis; if an ophthalmologist
diagnosed and treated a patient for uveal melanoma in the past, it is sufficient for a
clinical diagnosis

- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded for
non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) with
conventional techniques or as >= 10 mm (>= 1 cm) with spiral computed tomography (CT)
scan, magnetic resonance imaging (MRI), or calipers by clinical exam

- The study will be limited to patients who are chemotherapy naive; patients may have
received prior systemic or liver-directed local therapies for advanced uveal melanoma
as long as those treatments do not involve chemotherapy; this includes, but is not
limited to: immunotherapy, targeted therapy, transarterial embolization,
radiofrequency ablation, or cryoablation; treatment must be completed at least 28 days
prior to initiation of study therapy; radiation therapy is also allowed and must be
completed at least 28 days prior to initiation of study therapy; lesions treated via
radiation or liver-directed therapy may not be used as target lesions unless they
demonstrate growth over a minimum of 3 months on subsequent imaging

- All prior treatment-related toxicities must be Common Terminology Criteria for Adverse
Events (CTCAE) version (V) 5 grade =< 1 (except alopecia); certain exceptions apply,
such as immunotherapy-induced hypothyroidism or adrenal insufficiency or
panhypopituitarism requiring stable doses of hormone replacement or rash from prior
therapy

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2

- Life expectancy of greater than 3 months

- Leukocytes >= 3,000/uL

- Absolute neutrophil count >= 1,500/uL

- Platelets >= 100,000/uL

- Total bilirubin =< 1.5 x institutional upper limit of normal

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 x institutional upper limit of normal; =< 5 x institutional upper limit of
normal if liver metastasis present

- Creatinine =< institutional upper limit of normal OR creatinine clearance >= 60
mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry, for
the duration of study participation, and for 4 months after last CDX-011
(glembatumumab vedotin) dose; women of child-bearing potential must have a negative
serum pregnancy test within 14 days prior to start of protocol treatment; should a
woman become pregnant or suspect she is pregnant while she or her partner is
participating in this study, she should inform her treating physician immediately; men
and women treated or enrolled on this protocol must also agree to use adequate
contraception prior to the study, for the duration of study participation, and 4
months after completion of glembatumumab vedotin administration

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Patients with a history of another malignancy except for those who have been
disease-free for 2 years; patients with a history of definitively treated non-melanoma
skin cancer or squamous cell carcinoma of the cervix are eligible; patients with
definitively treated in-situ cancers are eligible, regardless of timeframe

- Patients with neuropathy > grade 1

- Patients who are receiving any other investigational agents; if the patient received a
previous investigational or other agent or treatment, a washout period of 4 weeks is
required

- Patients receiving any medications or substances that are substrates of cytochrome
P450 family 3, subfamily A, polypeptide 4 (CYP3A4) will be closely monitored for
toxicity; as part of the enrollment/informed consent procedures, the patient will be
counseled on the risk of interactions with other agents, and what to do if new
medications need to be prescribed or if the patient is considering a new
over-the-counter medicine or herbal product

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Human immunodeficiency virus (HIV)-positive patients on antiretroviral medications
that are CYP3A4 substrates will be closely monitored; HIV-positive patients will be
excluded if they have a cluster of differentiation 4 (CD4) count < 200

- Pregnant or nursing women

- Patients who have previously received CDX-011 (glembatumumab vedotin) or other
monomethyl auristatin E (MMAE)-containing agents

- Patients with a history of allergic reactions attributed to compounds of similar
composition to dolastatin or auristatin (e.g. Auristatin PHE, Auristatin PE, and
symplostatin)