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

Kartos Therapeutics

Status and phase: Completed; Phase 1

Conditions: Tumors; Melanoma; Oncology; Advanced Malignancy; Advanced Solid Tumors; Cancer; Oncology Patients

Treatments: Drug: Trametinib; Drug: Dabrafenib; Drug: AMG 232

Study type: Interventional

Funder types: Industry

Identifiers

NCT02110355

20120238

Details and patient eligibility

About

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.

Full 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.

Enrollment: 31 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

31 participants in 3 patient groups

AMG 232 with Trametinib and Dabrabenib

Experimental group

Description:

Arm 1 of Part 1 and 2 and Part 3

Treatment:

Drug: Trametinib

Drug: AMG 232

Drug: Dabrafenib

AMG 232 with Trametinib

Experimental group

Description:

Arm 2 of Part 1 and 2

Treatment:

Drug: Trametinib

Drug: AMG 232

Trametinib and Dabrafenib

Active Comparator group

Description:

Part 3

Treatment:

Drug: Trametinib

Drug: Dabrafenib