Study of Trametinib and Nab-paclitaxel in Patients With Melanoma

While treatment for melanoma has evolved in the last few years, advanced/metastatic melanoma
remains an aggressive disease with poor prognosis. Trametinib and nab-paclitaxel have
demonstrated single-agent activity in Phase III trials of patients with melanoma. The
investigators propose to investigate this drug combination in patients with advanced
unresectable or metastatic melanoma. This open-label Phase I study is designed to determine
the maximum tolerated dose (MTD), recommended Phase II dose (RP2D), and safety profile of
trametinib and nab-paclitaxel given in combination. Patients with melanoma and known BRAF
mutation status will receive escalating doses of trametinib and nab-paclitaxel to determine
the MTD. Once the MTD is determined an additional 6 patients will be treated at the MTD to
establish the dose for future studies.

Inclusion Criteria:

- Adults (≥18 years) with histologically or cytologically-confirmed advanced
unresectable or metastatic melanoma. BRAF mutation-positive and wild-type tumors are
allowed.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

- Adequate hematologic, renal, and hepatic function

- Life expectancy ≥12 weeks

- Any pre-existing neuropathy must be Adverse Events (CTCAE) version 4.0

Exclusion Criteria:

- More than 1 prior cytotoxic chemotherapy regimen in the metastatic setting

- Prior MEK inhibitor therapy (prior BRAF inhibitor allowed)

- Prior nab-paclitaxel (prior taxane allowed)

- Use of an investigational anti-cancer drug within 21 days or 5 half-lives (whichever
is shorter) prior to first dose. A minimum of 10 days after termination of
investigational drug is required. Any drug-related toxicity should have resolved to
Grade 1 or baseline.

- Symptomatic or untreated brain metastases

- History of retinal vein occlusion (RVO)