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

• ClinicalTrials.gov Identifier: NCT02440685
• Recruitment Status: Terminated
• First Posted: May 12, 2015
• Last Update Posted: August 14, 2018
• Sponsor: Asana BioSciences
• Information provided by (Responsible Party): Asana BioSciences

Study Description

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.

Condition or disease	Intervention/treatment	Phase
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	Drug: ASN002 Dose Escalation; Drug: ASN002 RD	Phase 1; Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 51 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: May 2015
• Actual Primary Completion Date: June 2018
• Actual Study Completion Date: July 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: ASN002 Dose Escalation; Multiple ascending doses of ASN002 will be administered to determine the maximum tolerated dose (MTD). Arm Closed	Drug: ASN002 Dose Escalation; Multiple ascending doses of ASN002 assigned by cohort
Experimental: ASN002 Recommended dose (RD) - DLBCL; ASN002 administered at the recommended dose in subjects with DLBCL. Arm Closed	Drug: ASN002 RD; Recommended dose of ASN002 from Part A
Experimental: ASN002 RD - Mantle Cell Lymphoma; ASN002 administered at the recommended dose in subjects with MCL. Arm Closed	Drug: ASN002 RD; Recommended dose of ASN002 from Part A
Experimental: ASN002 RD - Follicular Lymphoma; ASN002 administered at the recommended dose in subjects with FL.	Drug: ASN002 RD; Recommended dose of ASN002 from Part A
Experimental: ASN002 RD - Peripheral T-cell Lymphoma; ASN002 administered at the recommended dose in subjects with PTCL.	Drug: ASN002 RD; Recommended dose of ASN002 from Part A
Experimental: ASN002 RD - Myelofibrosis; ASN002 administered at the recommended dose in subjects with MF.	Drug: ASN002 RD; Recommended dose of ASN002 from Part A
Experimental: ASN002 RD - Chronic Lymphocytic Leukemia; ASN002 administered at the recommended dose in subjects with CLL.	Drug: ASN002 RD; Recommended dose of ASN002 from Part A

Outcome Measures

Primary Outcome Measures :

1. Part A: Determine the maximum tolerated dose (MTD) of ASN002 [ Time Frame: First 28 days ]
   The MTD will be determined by evaluating the number of subjects with treatment related dose limiting toxicity. This is the primary endpoint of Part A
2. Part B: evaluate the overall response rate (number of Complete Responses + Partial Responses) in subjects receiving ASN002 for the treatment of lymphoma, MF and CLL. [ Time Frame: First 6 months ]
   Change from baseline in the severity of disease, This is the primary endpoint for Part B.

Secondary Outcome Measures :

1. Calculate the pharmacokinetic area under the plasma concentration (AUC) of ASN002 [ Time Frame: First 29 days ]
   Calculate the amount of ASN002 in the bloodstream
2. Calculate the maximum plasma concentration (Cmax) at steady state. [ Time Frame: First 29 days ]
   Calculate the maximum amount of ASN002 in the bloodstream
3. Calculate the terminal elimination rate (T 1/2). [ Time Frame: First 29 days ]
   Calculate how fast ASN002 leaves the body

Other Outcome Measures:

1. To evaluate the change from baseline in the intensity of Phospho-STAT3 protein found in the blood of patients with lymphoma. [ Time Frame: First 29 days ]
   Evaluate the effect of ASN002 on tumor biomarkers
2. To evaluate the change from baseline in the intensity of Phospho-S6 protein found in the blood of patients with lymphoma. [ Time Frame: First 29 days ]
   Evaluate the effect of ASN002 on biomarkers
3. To evaluate the change from baseline in the intensity of Phospho-spleen tyrosine kinase (SYK) 525/526 protein found in the blood of patients with lymphoma.. [ Time Frame: First 29 days ]
   Evaluate the effect of ASN002 on biomarkers
4. To evaluate the change from baseline in the intensity of Phospho-extracellular signal-regulated kinases (ERK) protein found in the blood of patients with lymphoma. [ Time Frame: First 29 days ]
   Evaluate the effect of ASN002 on biomarkers
5. The number of patients who show a decrease from baseline in a serum panel of biomarkers of inflammation [ Time Frame: First 29 days ]
   Evaluate the effect of ASN002 on biomarkers

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Arizona

Arizona Oncology

Tempe, Arizona, United States, 85206

United States, California

University of California, San Francisco

San Francisco, California, United States, 94122

United States, Georgia

Winship Cancer Institute - Emory

Atlanta, Georgia, United States, 30322

United States, Michigan

University of Michigan

Ann Arbor, Michigan, United States, 48109

START - Midwest

Grand Rapids, Michigan, United States, 49503

United States, Mississippi

University of Mississippi Medical Center

Jackson, Mississippi, United States, 39216

United States, Ohio

Gabrail Cancer Center

Canton, Ohio, United States, 44718

United States, Oregon

Oregon Health & Science University

Portland, Oregon, United States, 97239

United States, Pennsylvania

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States, 19111

United States, Texas

MD Anderson Cancer Center

Houston, Texas, United States, 77030

South Texas Accelerated Research Therapeutics

San Antonio, Texas, United States, 78229

United States, Virginia

Virginia Cancer Specialists

Fairfax, Virginia, United States, 22031

Argentina

Hospital Universitario Austral

Buenos Aires, Derqui, Pilar, Argentina, 1629

Instituto Alexander Fleming

Ciudad Autonoma de Buenos Aires, Argentina, 1426

Sponsors and Collaborators

Asana BioSciences

Investigators

• Study Director: Niranjan Rao, PhD; Asana BioSciences

More Information

• Responsible Party: Asana BioSciences
• ClinicalTrials.gov Identifier: NCT02440685
• Other Study ID Numbers: ASN002-101
• First Posted: May 12, 2015
• Last Update Posted: August 14, 2018
• Last Verified: August 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Asana BioSciences:

DLBCL; FL; MCL; PTCL; MF; CLL

Additional relevant MeSH terms:

Lymphoma; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Leukemia, B-Cell; Primary Myelofibrosis; Chronic Disease; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Disease Attributes; Pathologic Processes