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

A Phase 1b/2a Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of AMG 232 Combined With Trametinib and Dabrafenib or Trametinib in Adult Subjects With Metastatic Cutaneous Melanoma

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02110355

Enrollment

Registered

2014-04-10

Start date

2014-12-19

Completion date

2018-12-27

Last updated

2021-03-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Advanced Malignancy, Advanced Solid Tumors, Cancer, Melanoma, Oncology, Oncology Patients, Tumors

Keywords

Metastatic melanoma

Brief summary

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.

Detailed description

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.

Interventions

DRUGAMG 232

Given as an oral tablet in escalating doses

DRUGTrametinib

Trametinib is an anti-cancer agent

DRUGDabrafenib

Dabrafenib is an anti-cancer agent

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Subject incidence of treatment-emergent adverse events, Results of safety laboratory tests, vital sign measurements, ECG measurements, PK parameters; Progression-free Survival Rate	36 months	Incidence and grade of treatment-emergent adverse events, including dose-limiting toxicities; AMG 232, trametinib, dabrafenib, and metabolite PK parameters; progression-free Survival

Secondary

Measure	Time frame	Description
Time to and duration of overall response and duration of stable disease measured by CT or MRI and assessed per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, Progression-free and Overall Survival	36 months	Objective Tumor Response

Countries

Australia, United States

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 26, 2026