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

Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02110355
• Other study ID #: 20120238
• Status: Completed
• Phase: Phase 1
• Start date: December 19, 2014
• Est. completion date: December 27, 2018

Study information

• Verified date: March 2021
• Source: Kartos Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: December 27, 2018
• Est. primary completion date: December 27, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Malignancy
• Advanced Solid Tumors
• Cancer
• Melanoma
• Neoplasms
• Oncology
• Oncology Patients
• Tumors

Intervention

Drug:
• AMG 232
Given as an oral tablet in escalating doses
• Trametinib
Trametinib is an anti-cancer agent
• Dabrafenib
Dabrafenib is an anti-cancer agent

Locations

Country	Name	City	State
Australia	Research Site	Melbourne	Victoria
Australia	Research Site	North Sydney	New South Wales
United States	Research Site	Aurora	Colorado
United States	Research Site	Boston	Massachusetts
United States	Research Site	Chapel Hill	North Carolina
United States	Research Site	Los Angeles	California
United States	Research Site	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
Kartos Therapeutics, Inc.	GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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