A Phase 1b Study Evaluating AMG 232 Alone and in Combination With Trametinib in Acute Myeloid Leukemia

Study Overview
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Brief Summary
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Open-label, sequential dose escalation and expansion study of AMG 232 in subjects with acute myeloid leukemia.

Official Title
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A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AMG 232 Alone and in Combination With Trametinib in Adult Subjects With Relapsed/Refractory Acute Myeloid Leukemia

Conditions
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Advanced Malignancy, Cancer, Oncology, Oncology Patients, Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: AMG 232
* Drug: Trametinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women > 18 years old Pathologically-documented, definitively-diagnosed AML that is relapsed or refractory to standard treatment, for which no standard therapy is available or the subject refuses standard therapy Ability to take oral medications and willing to record daily adherance to investigational product Adequate hematological, renal, hepatic, and coagulation laboratory assessments Exclusion Criteria: Active infection requiring intravenous (IV) antibiotics Prior participation in an investigational study (procedure or device) within 21 days of study day 1 Major surgery within 28 days of study day 1 Anti-tumor therapy within 14 days of study day 1

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AMG 232<br>AMG 232 is an anti-cancer agent | Drug: AMG 232<br>* Given an an oral tablet in escalating doses.<br>Drug: Trametinib<br>* Trametinib is an oral tablet given in a fixed dose.<br>|
| Experimental: AMG 232 & Trametinib<br>AMG 232 and Trametinib are anti cancer agents | Drug: Trametinib<br>* Trametinib is an oral tablet given in a fixed dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety and tolerability of AMG 232 | To evaluate the safety and tolerability of AMG 232 by reviewing clinically significant or ≥ Grade 3 changes in safety laboratory tests, physical examinations, ECGs, or vitals signs in all subjects enrolled. | 36 months | 
| Characterize the pharmacokinetics of AMG 232 alone and in combination with trametinib when administered orally. | PK parameters will include, but are not limited to, area under the plasma concentration versus time curve (AUC) and Peak Plasma Concentration (Cmax). | 36 months | 
| Determine the maximum tolerated dose of AMG 232 alone and in combination with trametinib, if possible. | The MTD is defined at the highest dose level with an observed incidence of dose limiting toxicity in < 33% of subjects enrolled in a cohort. | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Response | Complete response (CR), complete response with incomplete recovery (CRi), and duration response. | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML