NeoplasmsPhase 1NCT02961283
Study of ASN003 in Subjects With Advanced Solid Tumors
A Phase 1 study testing ASN003 ascending doses and ASN003 MTD in people with Neoplasms and Melanoma, run by Asana BioSciences at 5 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms, Melanoma, Colorectal Neoplasm
- What is being tested?
- ASN003 ascending doses and ASN003 MTD
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 5 sitesUnited States
- Study dates
- Oct 2016to Feb 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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;
Who cannot join
- 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:
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- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
START MidWest
Grand Rapids, Michigan, 49503
Cedars-Sinai Medical Center
Los Angeles, California, 90048
South Texas Accelerated Research Therapeutics
San Antonio, Texas, 78229
Moffitt Cancer Center
Tampa, Florida, 33612
About this study
Official title: A Phase 1, Open-label, Dose-finding and Cohort Expansion Study of ASN003 in Subjects With Advanced Solid Tumors
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)
Read the 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 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.
- Being tested
- ASN003 ascending doses, ASN003 MTD
- Keywords
- BRAF Kinases, PIK3CA protein, human
- Medical subject headings
- Neoplasms, Melanoma, Colorectal Neoplasms, Carcinoma, Non-Small-Cell Lung, Hereditary Sensory and Autonomic Neuropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ASN003 ascending dosesDrug
ASN003 MTDDrug
The highest safe and well tolerated dose selected from the doses tested in Part A of the study.
| Study group | Role | What they receive |
|---|---|---|
| ASN003 Dose Escalation | Experimental | Multiple ascending doses of ASN003 will be administered to determine the maximum tolerated dose (MTD). Receives: Drug: ASN003 ascending doses |
| ASN003 MTD - BRAFv600 melanoma | Experimental | ASN003 administered at the MTD in subjects with BRAF v600 mutated metastatic melanoma Receives: 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. Receives: 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. Receives: Drug: ASN003 MTD |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: Up to 1 year
Secondary outcomes (7)
Calculate the Pharmacokinetic Area Under the Curve
A plot of the concentration of ASN003 in blood plasma over time.
Measured: First 22 days
Calculate the Pharmacokinetic Maximum Concentration
The peak plasma concentration of ASN003
Measured: First 22 days
Calculate the Pharmacokinetic Half-life
The time required for ASN003 to lose half of its pharmacologic activity.
Measured: First 22 days
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
Measured: Up to 1 year
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.
Measured: Up to 1 year
Change in the status of non-measurable tumor lesions
Number of subjects that have resolution of non-measurable tumor lesions.
Measured: Up to 1 year
Appearance of new tumor lesions
Number of subjects with new lesions
Measured: Up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2016 (estimated)
- Study startOct 2016
- Primary completionFeb 2019
- Study completionFeb 2019
Why it stopped: reformulation
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Asana BioSciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Asana BioSciences, Study director, Asana BioSciences, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02961283
- Sponsor's protocol ID
- ASN003-101
- Status last verified
- May 2023
- First submitted
- 25 Oct 2016
- Last updated
- 9 May 2023
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-label, Dose-finding and Cohort Expansion Study of ASN003 in Subjects With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT02961283
- Acronym / sponsor ID
- ASN003-101
- Keywords
- BRAF Kinases, PIK3CA protein, human
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: reformulation
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Asana BioSciencesIndustry (pharma, biotech, devices)
- Study start
- Oct 2016
- Primary completion
- Feb 2019 (actual)
- Study completion
- Feb 2019 (actual)
- First posted
- 10 Nov 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| ASN003 Dose Escalation | Experimental | Drug: ASN003 ascending dosesMultiple ascending doses of ASN003 will be administered to determine the maximum tolerated dose (MTD). |
| ASN003 MTD - BRAFv600 melanoma | Experimental | Drug: ASN003 MTDASN003 administered at the MTD in subjects with BRAF v600 mutated metastatic melanoma |
| ASN003 MTD - BRAFv600 colon or lung cancer | Experimental | Drug: ASN003 MTDASN003 administered at the MTD in subjects with BRAFv600 mutated metastatic colorectal or non-small cell lung cancer. |
| ASN003 MTD - PIK3 pathway mutated cancers | Experimental | Drug: ASN003 MTDASN003 administered at the MTD in subjects who have mutations in PI3 kinase or loss of PTEN. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
- Screening hematology values of the following: absolute neutrophil count ≥ 1000/μL, platelets ≥ 100,000/μL, hemoglobin ≥ 10 g/dL (without transfusion support);
Key exclusion criteria (18 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ASN003 ascending doses | Drug | ASN003 Dose Escalation |
| ASN003 MTDThe highest safe and well tolerated dose selected from the doses tested in Part A of the study. | Drug | ASN003 MTD - BRAFv600 colon or lung cancer, ASN003 MTD - BRAFv600 melanoma, ASN003 MTD - PIK3 pathway mutated cancers |
Primary outcome
Part A: Determine the maximum tolerated dose (MTD) of ASN003
Time frame: First 21 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
Part B: evaluates the preliminary efficacy of ASN003 in subjects with selected BRAF and PI3 kinase mutated cancers
Time frame: Up to 1 year
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
7 secondary outcomes
Calculate the Pharmacokinetic Area Under the Curve
Time frame: First 22 days
Calculate the Pharmacokinetic Maximum Concentration
Time frame: First 22 days
Calculate the Pharmacokinetic Half-life
Time frame: First 22 days
Change from baseline in pharmacodynamic biomarkers
Time frame: Up to 1 year
Change in the size of measurable tumor lesions
Time frame: Up to 1 year
Change in the status of non-measurable tumor lesions
Time frame: Up to 1 year
Appearance of new tumor lesions
Time frame: Up to 1 year
Results and safety
The study was stopped early (reason given: reformulation). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Asana BioSciences study director
Asana BioSciences, LLC
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ASN003 ascending doses and ASN003 MTD in people with Neoplasms and Melanoma, run by Asana BioSciences at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: reformulation). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part A: Determine the maximum tolerated dose (MTD) of ASN003 (time frame: First 21 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2023.