B-Cell Chronic Lymphocytic Leukemia, B-Cell Leukemia, Chronic, B-Lymphocytic Leukemia, Chronic, Cancer, Chronic Idiopathic Myelofibrosis, Chronic Lymphocytic Leukemia, Idiopathic Myelofibrosis, Leukemia, Lymphocytic, Chronic, Leukemia, Lymphocytic, Chronic, B Cell, Lymphoma, B-cell, Lymphoma, Follicular, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Malignant, Lymphoma, Mantle-Cell, Lymphoma, Non-Hodgkin, Lymphoma, T Cell, Peripheral, Myelofibrosis, Neoplasm, Peripheral T-Cell Lymphoma, T-Cell Lymphoma, Peripheral, Tumor
Conditions
Keywords
DLBCL, FL, MCL, PTCL, MF, CLL
Brief summary
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
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.
Interventions
DRUGASN002 Dose Escalation
Multiple ascending doses of ASN002 assigned by cohort
DRUGASN002 RD
Recommended dose of ASN002 from Part A
Sponsors
Asana BioSciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Study terminated early so no all groups per protocol were conducted
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | First 29 days | Due to the early termination of the study, data for efficacy endpoints were insufficient for the planned efficacy analyses. |
Countries
Argentina, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 10 mg BID ASN002 10 mg BID | 3 |
| 20 mg BID ASN002 20 mg BID | 4 |
| 30 mg BID ASN002 30 mg BID | 3 |
| 40 mg BID ASN002 40 mg BID | 4 |
| 50 mg BID ASN002 50 mg BID | 7 |
| 75 mg BID ASN002 75 mg BID | 15 |
| 100 mg BID ASN002 100 mg BID | 5 |
| 80 mg QD ASN002 80 mg QD | 7 |
| 120 mg QD ASN002 120 mg QD | 3 |
| Total | 51 |
Baseline characteristics
| Characteristic | Total | 120 mg QD | 100 mg BID | 75 mg BID | 50 mg BID | 40 mg BID | 30 mg BID | 20 mg BID | 10 mg BID | 80 mg QD |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 65.2 years STANDARD_DEVIATION 11.78 | 74.0 years STANDARD_DEVIATION 7 | 63.2 years STANDARD_DEVIATION 13.81 | 65.1 years STANDARD_DEVIATION 9.92 | 62.9 years STANDARD_DEVIATION 20.39 | 62.0 years STANDARD_DEVIATION 6.68 | 66.3 years STANDARD_DEVIATION 5.51 | 67.5 years STANDARD_DEVIATION 9.47 | 65.0 years STANDARD_DEVIATION 19.31 | 65.6 years STANDARD_DEVIATION 10.33 |
| Disease Characteristic Lymphoma | 25 Participants | 1 Participants | 2 Participants | 11 Participants | 4 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 4 Participants |
| Disease Characteristic Myelofibrosis | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Disease Characteristic Solid tumor | 24 Participants | 2 Participants | 3 Participants | 2 Participants | 3 Participants | 2 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 0 Participants | 1 Participants | 3 Participants | 3 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants | 3 Participants | 4 Participants | 12 Participants | 4 Participants | 4 Participants | 1 Participants | 4 Participants | 2 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 50 Participants | 3 Participants | 5 Participants | 15 Participants | 7 Participants | 4 Participants | 3 Participants | 4 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Female | 20 Participants | 0 Participants | 1 Participants | 3 Participants | 4 Participants | 4 Participants | 2 Participants | 1 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Male | 31 Participants | 3 Participants | 4 Participants | 12 Participants | 3 Participants | 0 Participants | 1 Participants | 3 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 1 / 4 | 0 / 3 | 1 / 4 | 2 / 7 | 6 / 15 | 2 / 5 | 0 / 7 | 0 / 3 |
| other Total, other adverse events | 3 / 3 | 4 / 4 | 2 / 3 | 4 / 4 | 6 / 7 | 14 / 15 | 5 / 5 | 7 / 7 | 3 / 3 |
| serious Total, serious adverse events | 1 / 3 | 2 / 4 | 0 / 3 | 2 / 4 | 5 / 7 | 10 / 15 | 4 / 5 | 4 / 7 | 1 / 3 |
Outcome results
Primary
Objective Response Rate
Due to the early termination of the study, data for efficacy endpoints were insufficient for the planned efficacy analyses.
Time frame: First 29 days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 10 mg BID | Objective Response Rate | Complete response | 0 Participants |
| 10 mg BID | Objective Response Rate | Stable disease | 0 Participants |
| 10 mg BID | Objective Response Rate | Progressive disease | 3 Participants |
| 10 mg BID | Objective Response Rate | Partial response | 0 Participants |
| 10 mg BID | Objective Response Rate | Not evaluable | 0 Participants |
| 20 mg BID | Objective Response Rate | Not evaluable | 1 Participants |
| 20 mg BID | Objective Response Rate | Stable disease | 2 Participants |
| 20 mg BID | Objective Response Rate | Progressive disease | 1 Participants |
| 20 mg BID | Objective Response Rate | Complete response | 0 Participants |
| 20 mg BID | Objective Response Rate | Partial response | 0 Participants |
| 30 mg BID | Objective Response Rate | Stable disease | 1 Participants |
| 30 mg BID | Objective Response Rate | Complete response | 0 Participants |
| 30 mg BID | Objective Response Rate | Progressive disease | 2 Participants |
| 30 mg BID | Objective Response Rate | Partial response | 0 Participants |
| 30 mg BID | Objective Response Rate | Not evaluable | 0 Participants |
| 40 mg BID | Objective Response Rate | Not evaluable | 2 Participants |
| 40 mg BID | Objective Response Rate | Progressive disease | 2 Participants |
| 40 mg BID | Objective Response Rate | Partial response | 0 Participants |
| 40 mg BID | Objective Response Rate | Complete response | 0 Participants |
| 40 mg BID | Objective Response Rate | Stable disease | 0 Participants |
| 50 mg BID | Objective Response Rate | Complete response | 0 Participants |
| 50 mg BID | Objective Response Rate | Progressive disease | 4 Participants |
| 50 mg BID | Objective Response Rate | Not evaluable | 2 Participants |
| 50 mg BID | Objective Response Rate | Stable disease | 1 Participants |
| 50 mg BID | Objective Response Rate | Partial response | 0 Participants |
| 75 mg BID | Objective Response Rate | Partial response | 1 Participants |
| 75 mg BID | Objective Response Rate | Not evaluable | 12 Participants |
| 75 mg BID | Objective Response Rate | Stable disease | 1 Participants |
| 75 mg BID | Objective Response Rate | Progressive disease | 1 Participants |
| 75 mg BID | Objective Response Rate | Complete response | 0 Participants |
| 100 mg BID | Objective Response Rate | Stable disease | 0 Participants |
| 100 mg BID | Objective Response Rate | Not evaluable | 3 Participants |
| 100 mg BID | Objective Response Rate | Complete response | 0 Participants |
| 100 mg BID | Objective Response Rate | Partial response | 0 Participants |
| 100 mg BID | Objective Response Rate | Progressive disease | 2 Participants |
| 80 mg QD | Objective Response Rate | Partial response | 0 Participants |
| 80 mg QD | Objective Response Rate | Not evaluable | 1 Participants |
| 80 mg QD | Objective Response Rate | Complete response | 0 Participants |
| 80 mg QD | Objective Response Rate | Progressive disease | 4 Participants |
| 80 mg QD | Objective Response Rate | Stable disease | 2 Participants |
| 120 mg QD | Objective Response Rate | Partial response | 1 Participants |
| 120 mg QD | Objective Response Rate | Stable disease | 1 Participants |
| 120 mg QD | Objective Response Rate | Complete response | 0 Participants |
| 120 mg QD | Objective Response Rate | Not evaluable | 0 Participants |
| 120 mg QD | Objective Response Rate | Progressive disease | 1 Participants |