A Phase 1b/2a Study Evaluating AMG 232 in Metastatic Melanoma

The study will be conducted in 3 parts: Part 1 - Dose Escalation, Part 2 - Dose Expansion and
Part 3, a randomized Phase 2a.

In both part 1 and 2, subjects will be enrolled open-label into 1 of 2 arms. For both Arm 1
and Arm 2, the part 1 dose escalation is aimed at determining an AMG 232 maximum tolerated
dose (MTD) with a fixed dose of the combination drug(s) and evaluating safety, tolerability,
pharmacokinetics and pharmacodynamics of each combination. Part 2 dose expansion will enroll
subjects to receive therapy with a dose and schedule of AMG 232 selected from the
corresponding part 1 dose escalation. In part 2 subjects will be enrolled to confirm safety
and tolerability and to assess clinical activity prior to proceeding to Part 3, Phase 2a. In
Phase 2a, Subjects will be randomized open-label in a 1:1 ratio to receive AMG 232 in
combination with trametinib plus dabrafenib versus trametinib plus dabrafenib alone.

Inclusion Criteria: Subjects must have histologically or cytologically confirmed metastatic
cutaneous or mucosal melanoma, Able to swallow and retain orally administered medication,
Adequate hematological, renal, hepatic, and coagulation laboratory assessments Exclusion
Criteria: Clinically significant bleeding within 4 weeks of screening, Current use of
warfarin, factor Xa inhibitors, and direct thrombin inhibitors, Infection requiring
anti-infective treatments within 1 week of study enrollment, Anti-tumor therapy, Major
surgery within 28 days