A Study of ASN007 in Patients With Advanced Solid Tumors

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.