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.
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
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.
