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

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.

Study Overview

• Status: Completed
• Conditions: Melanoma; Cancer; Advanced Solid Tumors; Oncology; Tumors; Advanced Malignancy; Oncology Patients
• Intervention / Treatment: Drug: AMG 232; Drug: Trametinib; Drug: Dabrafenib

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.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • North Sydney, New South Wales, Australia, 2060
      • Research Site
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Research Site
• United States
  • California
    • Los Angeles, California, United States, 90095
      • Research Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Research Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Research Site
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AMG 232 with Trametinib and Dabrabenib; Arm 1 of Part 1 and 2 and Part 3	Drug: AMG 232; Given as an oral tablet in escalating doses; Drug: Trametinib; Trametinib is an anti-cancer agent; Drug: Dabrafenib; Dabrafenib is an anti-cancer agent
Experimental: AMG 232 with Trametinib; Arm 2 of Part 1 and 2	Drug: AMG 232; Given as an oral tablet in escalating doses; Drug: Trametinib; Trametinib is an anti-cancer agent
Active Comparator: Trametinib and Dabrafenib; Part 3	Drug: Trametinib; Trametinib is an anti-cancer agent; Drug: Dabrafenib; Dabrafenib is an anti-cancer agent

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Objective Tumor Response	36 months

Collaborators and Investigators

• Sponsor: Kartos Therapeutics, Inc.
• Collaborators: GlaxoSmithKline
• Investigators: Study Director: John Mei, Kartos Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2014
• Primary Completion (Actual): December 27, 2018
• Study Completion (Actual): December 27, 2018

Study Registration Dates

• First Submitted: April 8, 2014
• First Submitted That Met QC Criteria: April 8, 2014
• First Posted (Estimate): April 10, 2014

Study Record Updates

• Last Update Posted (Actual): March 26, 2021
• Last Update Submitted That Met QC Criteria: March 24, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Metastatic melanoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Neoplasms; Melanoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Trametinib; Dabrafenib
• Other Study ID Numbers: 20120238

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO