Study of ASN003 in Subjects With Advanced Solid Tumors

NCT02961283 | Terminated Phase 1

• 1 other identifier: ASN003-101
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 5

Brief 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)

Conditions

Neoplasms; Melanoma; Colorectal Neoplasm; Carcinoma, Non-small Cell Lung

Keywords

BRAF Kinases; PIK3CA protein, human

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (7)

• Calculate the Pharmacokinetic Area Under the Curve

  First 22 days

• Calculate the Pharmacokinetic Maximum Concentration

  First 22 days

• Calculate the Pharmacokinetic Half-life

  First 22 days

• Change from baseline in pharmacodynamic biomarkers

  Up to 1 year

• Change in the size of measurable tumor lesions

  Up to 1 year

Other Outcomes (1)

• Change in tumor mutational status

  Up to 1 year

Study Arms (4)

ASN003 Dose Escalation

EXPERIMENTAL

Multiple ascending doses of ASN003 will be administered to determine the maximum tolerated dose (MTD).

Drug: ASN003 ascending doses

ASN003 MTD - BRAFv600 melanoma

EXPERIMENTAL

ASN003 administered at the MTD in subjects with BRAF v600 mutated metastatic melanoma

Drug: ASN003 MTD

ASN003 MTD - BRAFv600 colon or lung cancer

EXPERIMENTAL

ASN003 administered at the MTD in subjects with BRAFv600 mutated metastatic colorectal or non-small cell lung cancer.

Drug: ASN003 MTD

ASN003 MTD - PIK3 pathway mutated cancers

EXPERIMENTAL

ASN003 administered at the MTD in subjects who have mutations in PI3 kinase or loss of PTEN.

Drug: ASN003 MTD

Interventions

ASN003 ascending doses DRUG

ASN003 Dose Escalation

ASN003 MTD DRUG

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

ASN003 MTD - BRAFv600 colon or lung cancer; ASN003 MTD - BRAFv600 melanoma; ASN003 MTD - PIK3 pathway mutated cancers

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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;

Sponsors & Collaborators

• Asana BioSciences: lead

Study Sites (5)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

START MidWest

Grand Rapids, Michigan, 49503, United States

Location

South Texas Accelerated Research Therapeutics

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Neoplasms; Melanoma; Colorectal Neoplasms; Carcinoma, Non-Small-Cell Lung; Hereditary Sensory and Autonomic Neuropathies

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Study Officials

• Asana BioSciences

  Asana BioSciences, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2016
• First Posted: November 10, 2016
• Study Start: October 1, 2016
• Primary Completion: February 1, 2019
• Study Completion: February 1, 2019
• Last Updated: May 9, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)