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.