A Phase 1, Open-Label, Dose-Finding Study of ASN007 in Patients with Advanced Solid Tumors

NOT ENROLLING
Protocol # :
18-228
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
Phase
I
Disease Sites
Neuroendocrine/Carcinoid
Gastroesophageal Junction
Gallbladder/Biliary
Lip, Oral Cavity and Pharynx
Esophagus
Stomach
Small Intestine
Colon
Rectum
Anus
Liver
Pancreas
Other Digestive Organ
Larynx
Lung
Other Respiratory and Intrathoracic Organs
Bones and Joints
Soft Tissue
Mycosis Fungoides
Other Skin
Breast
Cervix
Corpus Uteri
Ovary
Other Female Genital
Prostate
Other Male Genital
Urinary Bladder
Kidney
Other Urinary
Eye and Orbit
Brain and Nervous System
Thyroid
Unknown Sites
Ill-Defined Sites
Other Endocrine System
Kaposi's Sarcoma
Melanoma, Skin
Principal Investigator
Sullivan, Ryan, Joseph
Site Investigator
Hidalgo Medina, Manuel
Shapiro, Geoffrey, I.
Weiss, Glen
Site Research Nurses
Blaikie, Anna, Rose
Blaikie, Anna, Rose
Bowers, Mary, Ellen
Caramella, Anne
Cash, Hanna, Marie
Creaton, Eileen
DeGonge, Danielle
Delrosso, Alexandria, P.
Gotthardt, Susan, Jean
Harran, John
Lundin, Aishlinn
Lundquist, Debra
McIntyre, Casandra
Powers, Allison
QUINN, NICHOLAS

Trial Description

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.

Eligibility Requirements

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.

18-228