A Phase 1/2 Study To Evaluate ASN002 In Relapsed/Refractory Lymphoma And Advanced Solid Tumors

Study Overview
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Brief Summary
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This study is a dose escalation, and cohort expansion study in subjects with advanced cancer for which no standard therapy exists. Subjects must have received prior treatment for cancer that has not worked, or has stopped working.

Detailed Description
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The study will be conducted in two parts. Part A is a dose escalation study to determine a safe and tolerable dose of ASN002 for subjects with relapsed or refractory lymphoma, or advanced solid tumors. Part A will also characterize the pharmacokinetics and pharmacodynamics of ASN002 through blood sampling. Subjects in Part B will enroll subjects with four types of lymphoma Diffuse Large B-cell Lymphoma (DLBCL), Follicular Lymphoma (FL), Mantle Cell Lymphoma (MCL) and Peripheral T-cell lymphoma (PTCL). Additional groups of subjects with Myelofibrosis (MF) and Chronic Lymphocytic Leukemia (CLL) will be enrolled. Subjects will be treated with the highest safe and tolerable dose determined in Part A of the study to determine preliminary efficacy. Subjects may continue to receive ASN002 for up to 1 year in the absence of severe side effects or disease progression.

Official Title
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A Phase 1/2, Open-Label, Uncontrolled, Multiple Dose Escalation, Cohort Expansion Study To Evaluate The Safety, Tolerability, Pharmacokinetics And Preliminary Efficacy Of ASN002 In Relapsed/Refractory Lymphoma, Myelofibrosis, Chronic Lymphocytic Leukemia, And Advanced Solid Tumors

Conditions
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Lymphoma, Large B-Cell, Diffuse, Lymphoma, Mantle-Cell, Lymphoma, Follicular, Cancer, Neoplasm, Tumor, Lymphoma, Malignant, Lymphoma, B-cell, Lymphoma, Non-Hodgkin, B-Cell Chronic Lymphocytic Leukemia, B-Cell Leukemia, Chronic, B-Lymphocytic Leukemia, Chronic, Chronic Lymphocytic Leukemia, Leukemia, Lymphocytic, Chronic, Leukemia, Lymphocytic, Chronic, B Cell, Myelofibrosis, Chronic Idiopathic Myelofibrosis, Idiopathic Myelofibrosis, Lymphoma, T Cell, Peripheral, Peripheral T-Cell Lymphoma, T-Cell Lymphoma, Peripheral

Intervention / Treatment
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* Drug: ASN002 Dose Escalation
* Drug: ASN002 RD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent obtained prior to any study-related procedure being performed; Male or female subjects at least 18 years of age at the time of consent; Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2; Recovered from the reversible effects of prior antineoplastic therapy (with the exception of alopecia and Grade 1 neuropathy). Screening blood counts of the following: Absolute neutrophil count ≥ 1000/μL, Platelets ≥ 75,000/μL, Hemoglobin ≥ 8 g/dL (with transfusion support); Screening chemistry values of the following: Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 3.0 × upper limit of the normal (ULN), total bilirubin ≤ 1.5 × ULN, Creatinine ≤ 1.5 × ULN; At screening, life expectancy of at least 3 months; Subject is willing and able to comply with all protocol required visits and assessments; Male and female subjects of child-bearing potential must agree to use medically acceptable methods of birth control throughout the study and for thirty (30) days after the last dose of study medication. (Part A only) Histologically or cytologically confirmed metastatic and/or advanced solid tumors or lymphomas for which no standard therapy exists, or who are not eligible for standard treatment. Subjects must have received at least one prior therapy for their malignancy; (Part B only) Histologically confirmed DLBCL/MCL/FL/PTCL/MF/CLL on the basis of excisional lymph node or extranodal tissue biopsy; diagnosis of relapsed/refractory disease defined as 1) recurrence of disease after a Complete Response (CR), or 2) Partial Response (PR), Stable Disease (SD) at completion of treatment regimen preceding entry into study, subjects must not be candidates for standard therapy, subjects who have not received Stem Cell Translplant (SCT) must be ineligible to receive SCT. Exclusion Criteria Have received prior chemotherapy regimens within 4 weeks of Day 1; Have received prior treatment with monoclonal antibodies within 6 weeks of first dose of Day 1; Have had major surgery within 30 days prior to the start of Day 1; Received any investigational treatment within 4 weeks prior to the start of study medication; Have had an infection requiring the use of parenteral antibiotics within 14 days prior to the start of Day 1; Have known central nervous system metastasis or Central Nervous System lymphoma; Is receiving high dose corticosteroids (>10 mg prednisone daily or equivalent); Has known bleeding diathesis that would be a safety risk; Has a history of other malignancy within the 3 years prior to screening, except adequately treated basal cell or squamous cell carcinoma of the skin, or carcinoma in-situ; Has difficulty swallowing medications, or known history of malabsorption syndrome; Has a serious concurrent medical condition, such as: congestive heart failure New York Heart Association (NYHA) class III or IV or uncontrolled hypertension at screening, 12-Lead electrocardiogram (ECG) abnormalities considered by the investigator to be clinically significant including myocardial infarction, angioplasty, or cardiac stent placement within the last 6 months, HIV infection, known Hepatitis B or C infection. Subjects at high risk for Hepatitis B or C infection should have serology testing to rule out infection, a medical condition requiring the therapeutic use of anticoagulants. Known hypersensitivity to ASN002 or its excipients; Prior participation, i.e., receipt of study medication, in this study; Any condition that, in the opinion of the investigator, would impair the subject's ability to comply with study procedures; Female subjects that are pregnant or lactating. Part B only: Prior treatment with SYK or Janus Kinase (JAK) inhibitors, except MF subjects.

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: Parallel Assignment
Interventional Model Description: Study terminated early so no all groups per protocol were conducted
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A ASN002 Dose Escalation<br>Multiple ascending doses of ASN002 will be administered to determine the maximum tolerated dose (MTD). Arm Closed | Drug: ASN002 Dose Escalation<br>* Multiple ascending doses of ASN002 assigned by cohort<br>|
| Experimental: Part B ASN002 Recommended dose (RD)<br>ASN002 administered at the recommended dose | Drug: ASN002 RD<br>* Recommended dose of ASN002 from Part A<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Due to the early termination of the study, data for efficacy endpoints were insufficient for the planned efficacy analyses. | First 29 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DLBCL, FL, MCL, PTCL, MF, CLL