A Phase 1b/2a Study Evaluating AMG 232 in Metastatic Melanoma
A Phase 1b/2a Study Evaluating AMG 232 in Metastatic Melanoma
Phase 1b/2a, open-label, sequential dose escalation and expansion study of AMG 232 in
 combination with trametinib and dabrafenib in subjects with metastatic melanoma followed by a
 direct comparison of AMG 232 combined with trametinib and dabrafenib versus trametinib
 combined with dabrafenib alone.
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.

 Only Part 1 of the study was enrolled and the study did not proceed into Phase 2.
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