A Study of ASN007 in Patients With Advanced Solid Tumors

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.