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

• Sponsor: Kartos Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02110355
• Collaborator: GlaxoSmithKline (Industry)
• Enrollment: 31
• Locations: 7
• Arms: 3
• Actual Duration (Months): 48.3
• Patients Per Site: 4.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Malignancy; Advanced Solid Tumors; Cancer; Oncology; Oncology Patients; Tumors; Melanoma	Drug: AMG 232; Drug: Trametinib; Drug: Dabrafenib	Phase 1

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 Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Dec 19, 2014
• Actual Primary Completion Date: Dec 27, 2018
• Actual Study Completion Date: Dec 27, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Los Angeles	California	United States	90095
2	Research Site	Aurora	Colorado	United States	80045
3	Research Site	Boston	Massachusetts	United States	02114
4	Research Site	Chapel Hill	North Carolina	United States	27599
5	Research Site	Nashville	Tennessee	United States	37232
6	Research Site	North Sydney	New South Wales	Australia	2060
7	Research Site	Melbourne	Victoria	Australia	3000

Sponsors and Collaborators

• Kartos Therapeutics, Inc.
• GlaxoSmithKline

Investigators

• Study Director: John Mei, Kartos Therapeutics

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Kartos Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT02110355
• Other Study ID Numbers: 20120238
• First Posted: Apr 10, 2014
• Last Update Posted: Mar 26, 2021
• Last Verified: Mar 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Kartos Therapeutics, Inc.: Metastatic melanoma
• Additional relevant MeSH terms: Neoplasms; Melanoma; Trametinib; Dabrafenib

Study Results

No Results Posted as of Mar 26, 2021