A Phase 1 Study Evaluating AMG 232 in Advanced Solid Tumors or Multiple Myeloma

Study Overview
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Brief Summary
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First in human, open-label, sequential dose escalation and expansion study of AMG 232 in subjects with advanced solid tumors or multiple myeloma

Detailed Description
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Study Design: This is an open-label, dose exploration study evaluating AMG 232 in subjects with advanced p53WT solid tumors or multiple myeloma. The study will be conducted in 2 parts: Part 1 - Dose Exploration (parts 1a, 1b and 1c) and Part 2 - Dose Expansion. Part 1a is aimed at evaluating the safety, tolerability, PK and PD of AMG 232 and determining the MTD of a 7-day once daily (QD) dosing schedule in subjects with advanced solid tumors using a practical continuous reassessment method (CRM). Part 1b will evaluate the safety and tolerability of 3-day QD dosing schedule (or alternate dosing schedule based upon emerging data) with a particular emphasis on evaluating the tolerability of daily doses equal to or higher than the part 1a MTD in subjects with solid tumors or multiple myeloma. Part 1c will evaluate the safety and tolerability of 7-day twice daily (BID) dosing schedule with daily cumulative doses equal to or higher than the part 1a MTD in subjects with solid tumors. The dose expansion part of the study (Part 2) can open once the MTD has been determined in Part 1a. Part 2, part 1b and part 1c can be explored in parallel. The dose expansion part will consist of up to 85 additional subjects with specific tumors harboring MDM2 amplification (liposarcoma [LPS], gliobastoma [ GBM ] and all other solid tumors) or potentially harboring MDM2 overexpression (ER+ metastatic breast cancer) and a group of subjects with multiple myeloma.

Official Title
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A Phase 1 First-in-Human Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 232 in Adult Subjects With Advanced Solid Tumors or Multiple Myeloma

Conditions
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Advanced Malignancy, Advanced Solid Tumors, Cancer, Oncology, Oncology Patients, Tumors, Glioblastoma, Multiple Myeloma

Intervention / Treatment
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* Drug: AMG 232


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women > 18 years old Pathologically documented, definitively diagnosed, advanced solid tumor that is refractory to standard treatment, or which no standard therapy is available, or the subject refuses standard therapy or multiple myeloma Willing to undergo pre-dose core needle tumor biopsies or bone marrow aspirate for subjects with multiple myeloma. 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 brain metastases For solid tumor-History or presence of hematological malignancies unless curatively treated with no evidence of disease for greater than or equal to 5 years Active infection requiring intravenous (IV) antibiotics Anti-tumor therapy Therapeutic or palliative radiation therapy within 30 days of starting treatment Currently enrolled in another investigational device or drug study

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
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>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of AMG 232 | Subject incidence of adverse events, dose limiting toxicities, and clinically significant changes in vital signs, weight, ECGs and clinical laboratory tests | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Tumor Response | 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, for multiple myeloma using IMWG response criteria | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Solid Tumors, Multiple Myeloma