Study of an Investigational Drug, ASP3026, in Patients With Advanced Malignancies (Solid Tumors and B-Cell Lymphoma)

Study Overview
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Brief Summary
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This study is to evaluate the safety and anti-tumor activity of ASP3026 in patients with advanced malignancies (solid tumors and B-cell lymphoma).

Detailed Description
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This study will be conducted using a traditional 3 + 3 dose escalation study design. Enrollment of at least 3 subjects is planned for each dosing cohort until the Maximum Tolerated Dose (MTD) is determined. Up to three additional subjects per cohort may be enrolled if each additional subject is known to be positive for Anaplastic Lymphoma Kinase (ALK) or Proto-Oncogene Tyrosine-Protein Kinase ROS (ROS) abnormalities. The decision to expand a cohort or dose escalate will be based on the occurrence of dose limiting toxicities (DLTs) in Cycle 1 that are considered by the Investigator to be related (possibly or probably) to ASP3026. Intra-subject dose escalation will be allowed at the discretion of the investigators. The Safety Data Review Committee may elect to enroll additional subjects in a cohort to further evaluate the dose level. Once the MTD is determined, approximately 20 additional subjects with Anaplastic Lymphoma Kinase (ALK) abnormalities will be enrolled at the Recommended Phase 2 Dose. Each cycle will include 28 days of continuous dosing with ASP3026. Treatment with ASP3026 may continue until one of the discontinuation criteria is met.

Official Title
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A Phase 1, Multicenter, Open-Label, Dose Escalation Study of ASP3026 in Subjects With Advanced Malignancies

Conditions
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Advanced Malignancies, Positive for Anaplastic Lymphoma Kinase, Positive for Proto-Oncogene Tyrosine-Protein Kinase ROS, Solid Tumor, B-Cell Lymphoma

Intervention / Treatment
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* Drug: ASP3026


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 Histologically or cytologically confirmed diagnosis of a relapsed/refractory solid tumor or B-cell lymphoma and meets at least 1 of the following criteria: Disease progression despite standard therapies No standard therapies are available or such therapies are not anticipated to result in a durable response Standard therapies are considered unsuitable or have been refused Able to take oral medications Life expectancy > 12 weeks For the expansion cohort of the study, all subjects must be confirmed to be positive for ALK gene abnormalities Subjects with stable brain metastasis will be allowed Exclusion Criteria: Active central nervous system (CNS) metastases or leptomeningeal involvement as assessed through medical history review and physical examination (dose escalation subjects only) Known history of a positive test for hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) Known hereditary or acquired immunodeficiency syndrome or human immunodeficiency virus (HIV) infection Cardiac arrhythmias > Grade 1 using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v. 4.03 Class 3 or 4 New York Heart Association congestive heart failure, acute coronary syndrome, myocardial infarction or cerebrovascular accident within 6 months prior to Cycle 1, Day 1 Inadequate bone marrow, renal, and/or hepatic function Confirmed active peptic ulcer disease or history of gastrointestinal bleeding within the past 3 months Known history of long QT syndrome

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: ASP3026<br>Subjects will receive escalated doses of ASP3026 to determine the maximum tolerated dose (MTD) | Drug: ASP3026<br>* Tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of ASP3026 assessed by recording of adverse events, laboratory assessments, vital signs, electrocardiograms (ECGs) and clinical observations |  | Up to 30 days after last subject discontinues treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic assessment through analysis of blood and urine samples |  | Up to Day 29 | 
| Objective response rate (ORR) | Objective response rate is the proportion of subjects who experience complete response/remission (CR) or partial response/remission (PR) | 30 Days after the last subject discontinues treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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B-cell Lymphoma, Advanced Malignancies, Anaplastic Lymphoma Kinase (ALK), ASP3026, Solid Tumor