Study of ASN003 in Subjects With Advanced Solid Tumors

Melanoma Clinical Trial

Official title:

A Phase 1, Open-label, Dose-finding and Cohort Expansion Study of ASN003 in Subjects With Advanced Solid Tumors

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02961283
• Other study ID #: ASN003-101
• Status: Terminated
• Phase: Phase 1
• Start date: October 2016
• Est. completion date: February 2019

Study information

• Verified date: May 2023
• Source: Asana BioSciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study is divided into two parts. The first part of the study will test various doses of ASN003 to find out the highest safe dose to test in three specific groups.

The second part of the study will test how well ASN003 can control cancer. Subjects will be enrolled into one of three groups.

Group 1: metastatic or recurrent melanoma with documented BRAFV600 mutation (n=20 evaluable patients) Group 2: metastatic colorectal cancer (CRC), or advanced non-small cell lung cancer (NSCLC) with documented BRAFV600 mutation (n=14 evaluable patients) Group 3: advanced solid tumors with documented PI3K pathway alterations (PIK3CA mutation or PTEN loss) (n=14 evaluable patients)

Description:

The study will be conducted in two parts. Part A is a dose escalation study to determine a safe and tolerable dose of ASN003 for subjects with advanced solid tumors. Part A will also characterize the pharmacokinetics and pharmacodynamics of ASN003 through blood sampling and optional biopsies.. Part B will only enroll subjects in three groups:

Group 1: subjects who have metastatic or recurrent melanoma with the BRAFv600 mutation.

Group 2: subjects who have advanced or metastatic non-small cell lung cancer, or colorectal cancer with the BRAFv600 mutation.

Group 3: subjects who have advanced or metastatic cancers with phosphatidylinositide 3-kinases (PI3K) mutations, or phosphatase and tensin homolog (PTEN) loss mutation. 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 ASN003 for up to 1 year in the absence of severe side effects or disease progression.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 24
• Est. completion date: February 2019
• Est. primary completion date: February 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• written informed consent obtained prior to any study-related procedures.

• Eastern Cooperative Oncology Group Performance Status: 0-1

• Part A only: Histologically or cytologically confirmed metastatic and/or advanced solid tumors with documented progressive disease for whom no further standard therapy is indicated.

• Part B only: 5. Histologically or cytologically confirmed, molecularly selected (i.e. BRAFV600 positive and/or PI3K mutation positive) advanced solid tumors. Prior molecular characterization should be based using a regulatory approved assay or analytically validated assay.

• Group 1: BRAFV600 positive metastatic or recurrent melanoma after failure of prior treatment with standard therapy such as a checkpoint inhibitor and an approved B-RAF inhibitor (vemurafenib or dabrafenib)

• Group 2: BRAFV600 positive metastatic colorectal carcinoma (CRC), or advanced non-small cell lung carcinoma (NSCLC) after failure of at least two lines of prior standard therapy or for whom no further standard therapy is indicated.

• Group 3: Advanced solid tumors with PI3K pathway alterations (PIK3CA mutation or PTEN loss) after failure of at least one line of prior standard therapy or for whom no further standard therapy is indicated. Prior treatment may not include inhibitors of the PI3K pathway.

• Screening hematology values of the following: absolute neutrophil count = 1000/µL, platelets = 100,000/µL, hemoglobin = 10 g/dL (without transfusion support);

• Screening chemistry values of the following: alanine aminotransferase (ALT) and aspartate transaminase (AST) = 3.0 × upper limit of the normal reference range (ULN), total bilirubin = 2 × ULN, creatinine = 1.5 × ULN, fasting blood glucose < 140 mg/dL, hemoglobin A1C = ULN, albumin = 2.8 g/dL.

• Screening fasting lipid panel: LDL cholesterol < 190 mg/dL, triglycerides < 300 mg/dL

• Subject is willing and able to comply with all protocol required visits and assessments, including biopsy if assigned to the MTD expansion cohort;

Exclusion Criteria:

• Have received prior chemotherapy, other investigational therapy, or major surgery within 4 weeks of Day 1;

• Have received oral anti-cancer therapy with oral tyrosine kinase inhibitors within 14 days or 5 half-lives, whichever is longer.

• Have received prior treatment with monoclonal antibodies within 6 weeks of first dose of Day 1;

• Subject has received a live virus vaccine within the previous 8 weeks.

• Have known central nervous system metastasis or primary tumor (Part A). Previously-treated, CNS metastasis is permitted in Part B. CNS metastasis must be small, discrete metastasis; stable for at least 30 days without the need for concomitant prednisone for symptom management. No leptomeningeal disease is allowed. Is receiving therapeutic doses of corticosteroids (>20 mg prednisone daily or equivalent);

• Has a serious concurrent medical condition such as:

• history of Diabetes Mellitus, type 1 or type 2,

• known autoimmune disease, known bleeding diathesis, history of congestive heart failure New York Heart Association (NYHA) class III or IV;

• uncontrolled hypertension (systolic BP = 139 mmHg or diastolic BP = 89 mmHg) at screening, despite optimal antihypertensive therapy,

• clinically significant heart disease including but not limited to: myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or known cardiac ejection fraction measurement of < 50 %;

• history or family history of long QT syndrome; 12-Lead electrocardiogram (ECG) abnormalities considered by the investigator to be clinically significant or QTcF = 450 milliseconds, regardless of clinical significance, at screening. Abnormal ECG may be confirmed with one repeat assessment. For subjects with QTcF = 450 msec on initial ECG, the mean of the two QTcF assessments will determine eligibility;

• uncontrolled psychiatric illness;

• serious persistent infection within 14 days prior to the start of study medication;

• known gastrointestinal disease or condition which may affect the absorption of ASN003;

• known active or symptomatic viral hepatitis, chronic liver disease or liver cirrhosis;

• known glaucoma or other pre-existing ocular conditions that may put the patient at risk for ocular toxicities.

• any known condition or situation which may put the patient at significant risk, may confound the study results, or may interfere significantly with subject's participation in the study

• Female subjects who are pregnant or breast feeding

Related Conditions & MeSH terms

• Carcinoma, Non-small Cell Lung
• Carcinoma, Non-Small-Cell Lung
• Colorectal Neoplasm
• Colorectal Neoplasms
• Melanoma
• Neoplasms

Intervention

Drug:
• ASN003 ascending doses

• ASN003 MTD
The highest safe and well tolerated dose selected from the doses tested in Part A of the study.

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	START MidWest	Grand Rapids	Michigan
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	South Texas Accelerated Research Therapeutics	San Antonio	Texas
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Asana BioSciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in tumor mutational status	Tumor biopsy samples will be tested to look for changes	Up to 1 year
Primary	Part A: Determine the maximum tolerated dose (MTD) of ASN003	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	First 21 days
Primary	Part B: evaluates the preliminary efficacy of ASN003 in subjects with selected BRAF and PI3 kinase mutated cancers	Evaluation of the overall disease status using the RECIST 1.1 terms of complete response, partial response, stable disease, and progressive disease. This is the primary endpoint for Part B	Up to 1 year
Secondary	Calculate the Pharmacokinetic Area Under the Curve	A plot of the concentration of ASN003 in blood plasma over time.	First 22 days
Secondary	Calculate the Pharmacokinetic Maximum Concentration	The peak plasma concentration of ASN003	First 22 days
Secondary	Calculate the Pharmacokinetic Half-life	The time required for ASN003 to lose half of its pharmacologic activity.	First 22 days
Secondary	Change from baseline in pharmacodynamic biomarkers	Pre-dose and post-dose pharmacodynamic biomarkers in plasma and tumor biopsy will be compared to assess signs of pharmacodynamic activity	Up to 1 year
Secondary	Change in the size of measurable tumor lesions	Change from baseline in the sum of the longest dimension in centimeters of each measurable lesion, the presence/absence of lesions that cannot be measured in centimeters, or the presence of new lesions.	Up to 1 year
Secondary	Change in the status of non-measurable tumor lesions	Number of subjects that have resolution of non-measurable tumor lesions.	Up to 1 year
Secondary	Appearance of new tumor lesions	Number of subjects with new lesions	Up to 1 year