Clinical trial NCT03415126: A Study of ASN007 in Patients With Advanced Solid Tumors
Official title: A Phase 1, Open-Label, Dose-Finding Study Of ASN007 In Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Malignancy
Neoplasia
Neoplasm
Neoplasm Metastasis
Colon Cancer
Colonic Neoplasms
Colon Cancer Liver Metastasis
Metastatic Cancer
Metastatic Melanoma
Metastatic Colon Cancer
Metastatic Lung Cancer
Non Small Cell Lung Cancer Metastatic
Pancreatic Cancer
Pancreas Cancer
Pancreas Adenocarcinoma
Pancreas Neoplasm
Metastatic Nonsmall Cell Lung Cancer
Metastatic Pancreatic Cancer
Keywords: KRAS mutant
NRAS mutant
BRAF mutant
HRAS mutant
ERK 1/2 inhibitor
Lead sponsor: Asana BioSciences
Sponsor class: INDUSTRY
First posted: 2018-01-30
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study is divided into two parts. The first part of the study will test various doses of ASN007 to find out the highest safe dose to test in five specific groups. The second part of the study will test how well ASN007 can control cancer.

Detailed description: Part A is a dose escalation study to determine a safe and tolerable dose of ASN007 for patients with advanced solid tumors. Part A will also describe how the body works on ASN007(pharmacokinetics) and the effects of ASN007 on the body (pharmacodynamics) of ASN007, through blood sampling and optional biopsies..

Part B of the study will enroll patients with particular tumor types and genetic mutations for treatment at the Recommended Phase 2 Dose. Part B will enroll patients in five groups of fifteen patients each:

Group 1: Patients with metastatic BRAF mutated melanoma Group 2: Patients with metastatic NRAS and HRAS mutated solid tumors Group 3: Patients with metastatic KRAS mutated colorectal cancer (CRC) Group 4: Patients with metastatic KRAS mutated non-small cell lung cancer (NSCLC) Group 5: Patients with metastatic pancreatic ductal adenocarcinoma (PDAC) Patients with melanoma will be required to have pre-dose and post-dose biopsies.

Group 6: Patients with metastatic MEK1, BRAF V600E, non-BRAF V600E solid tumors or BRAF fusions without prior treatment with BRAF, MEK, ERK inhibitors

Eligibility criteria: Inclusion Criteria:

* Written informed consent obtained prior to any study-related procedure being performed;
* Male or non-pregnant, non-lactating female patient at least 18 years of age at the time of consent;
* Eastern Cooperative Oncology Group Performance Status 0-1 (Part A) and PS 0-2 (Part B)
* Histologically or cytologically confirmed
* advanced or metastatic solid tumor (Part A)
* Group 1: BRAF mutant melanoma (Part B)
* Group 2: NRAS or HRAS mutant solid tumors(Part B)
* Group 3: KRAS mutant CRC.(Part B)
* Group 4: KRAS mutant NSCLC (Part B)
* Group 5: Pancreatic Ductal Adenocarcinoma (Part B)
* Progressive disease after failure of or intolerant to all available standard systemic treatments that have shown a documented benefit in overall survival for their respective tumor type.
* Measurable or evaluable disease per RECIST v1.1
* Screening hematology values of the following:
* absolute neutrophil count ≥ 1000/μL,
* platelets ≥ 100,000/μL,
* hemoglobin ≥ 9 g/dL
* 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,,
* albumin ≥ 2.8 g/dL.
* Screening heart function lab test
* creatinine kinase - MB, troponin-I, and troponin-T within normal limits
* Subject is willing and able to comply with all protocol required visits and assessments, including biopsy if assigned.

Exclusion Criteria:

* Prior treatment with ASN007 or another ERK1/2 inhibitor
* Known hypersensitivity to ASN007 or its excipients;
* Part B: Prior treatment with a RAF or MEK pathway inhibitor, except BRAFmutant melanoma (Group 1)
* Prior chemotherapy, targeted therapy or monoclonal antibody therapy within 3 weeks of start of study treatment (Day1), or 5 half-lives, whichever is shorter.
* Concurrent or prior bone marrow factors (e.g. G-CSF, GM-CSF or erythropoietin) within 3 weeks prior to Day 1 of treatment.
* Febrile neutropenia or serious persistent infection within 2 weeks prior to Day 1 of treatment
* Failure to recover from major surgery or traumatic injury within 4 weeks or minor surgery within 2 weeks prior to Day 1 of treatment.
* History of or current evidence / risk of retinal vein occlusion (RVO) central serous retinopathy (CSR), or glaucoma with intraocular pressures ≥ 21 mmHg or other pre-existing ocular conditions that may put the patient at risk for ocular toxicities
* Known central nervous system (CNS) primary tumor, CNS metastases or carcinomatous meningitis (Part A). Patients may be enrolled with CNS metastasis in certain circumstances in Part B.
* Clinically significant heart disorders including an ejection fraction of \< 50%
* Other serious uncontrolled conditions such as fungal, bacterial or viral infection; HIV, Hepatitis B or C, bleeding disorders, interstitial lung disease,
* Any other condition that might place the patient at undue risk.

Primary outcomes:
measure: Part A: Determine the maximum tolerated dose (MTD) of ASN007
timeFrame: First 21 days
measure: Part B: evaluate the overall response rate (number of Complete Responses + Partial Responses) in subjects receiving ASN007 for the treatment of metastatic melanoma, CRC, NSCLC, or pancreatic cancer.
timeFrame: First 6 months
Secondary outcomes:
measure: Calculate the pharmacokinetic area under the plasma concentration (AUC) of ASN007
timeFrame: First 21 days
measure: Calculate the maximum plasma concentration (Cmax) at steady state.
timeFrame: First 21 days
measure: Calculate the terminal elimination rate (T 1/2).
timeFrame: First 21 days
Other outcomes:
measure: To evaluate the change from baseline in the intensity of phosphorylated ribosomal S6 kinase (RSK) found in tumor biopsies.
timeFrame: Through the study, average 6 months
measure: Evaluate the change from baseline in the amount of circulating tumor DNA
timeFrame: Every 8 weeks for the first 24 weeks, then every 12 weeks for up to 1 year
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
Study officials:
affiliation: Asana BioSciences
name: Medical Monitor
role: STUDY_DIRECTOR
References: