SLC-391 is a novel, potent and specific small molecule inhibitor of receptor tyrosine kinase
AXL with desirable potency and pharmaceutical properties. It has demonstrated
antiproliferative activity against different tumour cell lines in vitro and efficacy in
different animal models including nonsmall cell lung cancer (NSCLC), chronic myeloid leukemia
(CML) and (acute myeloid leukemia (AML) models. It has also exhibited strong synergy with
other approved targeted therapies in different animal models.
This is the first clinical study with SLC-391. The goals of this study are to evaluate the
safety, pharmacokinetic (PK), and pharmacodynamic profile of SLC-391, and then to identify a
safe and pharmacologically active dose for evaluation in subsequent cohorts or clinical
studies. In addition, change from baseline of possible blood biomarkers (soluble AXL and Gas
6) may be evaluated.
This is an open-label, multicentre, phase 1, dose-escalation, dose-expansion, first in human
study to evaluate the safety of SLC-391 administered orally (once-daily) in 21-day cycles to
subjects with advanced solid tumours.
- Be 18 years of age or older at the time of signing the informed consent.
- Have a histologically or cytologically confirmed diagnosis of a solid tumour
malignancy that is advanced and/or metastatic or unresectable and for which standard
or curative measures do not exist or are no longer effective.
- Have measurable disease as per the Response Evaluation Criteria in Solid Tumours
- Have a performance status score of 0 or 1 according to the Eastern Cooperative
Oncology Group (ECOG) scale.
- Be able to ingest oral medication.
- Have adequate organ function,
- Have recovered to ≤ grade 1 from the effects of any prior cancer therapy, except for
alopecia; irreversible neuropathy should have recovered to ≤ grade 2. Toxic effects
also include laboratory test abnormalities.
- Be afebrile at baseline prior to SLC-391 administration (ie, < 38.0 °C).
- Have a life expectancy greater than 3 months, in the Investigator's opinion.
- The following time must have elapsed between previous therapy for cancer and first
dose of SLC-391:
1. At least 4 weeks since previous cancer-directed therapy, including
investigational agents or devices (cytotoxic agents, targeted therapy including
monoclonal antibodies, immunotherapy, hormonal therapy, and prior radiotherapy)
with the exception of nitrosoureas/mitomycin where 6 weeks since these therapies.
2. At least 4 weeks or 5 times the elimination half-life (whichever is shortest) of
any investigational agents, including drugs, biologics, or combination products.
3. At least 4 weeks since any major surgery.
- Sexually active women of child-bearing potential and sexually active male subjects
with a female partner of child-bearing potential or pregnant must agree to use
acceptable double-barrier methods of contraception to avoid pregnancy from screening,
for the duration of the study, and for 3 months after the last dose of study drug.
Male subjects must also agree to refrain from donating sperm for the duration of the
study, including during dose interruptions and for 3 months after the last dose
- Be able and willing to provide signed informed consent and comply with the
requirements, assessment schedule, dosing schedule, and restrictions listed in the
informed consent form (ICF) and study protocol.
- Prior use of any AXL inhibitor
- Localised or metastatic prostate cancer subjects who are concurrently receiving
anti-cancer hormonal therapy.
- Refractory nausea and vomiting, chronic gastrointestinal (GI) diseases, GI bleeding,
ulceration, or perforation within 12 weeks prior to the first dose of the study drug,
or significant bowel resection that would preclude adequate absorption, distribution,
metabolism, or excretion of the study drug.
- History of myocardial infarction, unstable angina, congestive heart failure (New York
Heart Association class ≥ III/IV), cerebrovascular accident, transient ischaemic
attack, limb claudication at rest, stroke or subarachnoid hemorrhage, coagulopathy,
deep vein thrombosis, pulmonary embolism in the 6 months prior to consent.
- Uncontrolled hypertension (≥ 160/100 mmHg).
- History of or ongoing symptomatic dysrhythmias, uncontrolled atrial or ventricular
arrhythmias, or heart block (excluding 1st degree block, consisting of PR interval
prolongation only). Controlled atrial fibrillation is allowed.
- QTcF interval > 480 msec.
- Severe respiratory illness requiring supplemental oxygen or that significantly impacts
functional status in daily life including a known history of active tuberculosis
- History of significant weight loss (≥ 7 kgs/15 lbs) within 4 weeks prior to the first
dose of study drug.
- Immunocompromised or those with known autoimmune conditions, known human
immunodeficiency virus (HIV), or known active hepatitis (according to diagnostic
serology results that are positive for active hepatitis B [HBV; including core
antibody and surface antigen; AntiHBc and HBsAg, respectively] or hepatitis C [HCV]
infection). Note: If any serology is positive, qualitative polymerase chain reaction
will be obtained and results must be negative for eligibility.
- Active uncontrolled infection, or an unstable or severe intercurrent medical condition
that requires treatment.
- History of solid organ transplant or bone marrow transplant.
- Any condition or illness that, in the opinion of the Investigator, would compromise
subject safety or interfere with the evaluation of the safety of the study drug and
jeopardises compliance with the protocol and study visits.
- Brain metastases and central nervous system disease including leptomeningeal disease.
- History of prior malignancy, except for the following: curatively treated basal or
squamous cell carcinoma of the skin (nonmelanoma skin cancer); cervical or vaginal
intra-epithelial neoplasia; or noninvasive breast cancer in situ at screening.
Subjects with other curatively treated malignancies who have had no evidence of
metastatic disease and a > 2-year disease-free interval may be enrolled after approval
by the Medical Monitor or SignalChem Lifesciences (SLC) designee.
- Females who are pregnant, planning to become pregnant, or breastfeeding.
- Hypersensitivity to the study drug or excipients (lactose, microcrystalline cellulose,
magnesium stearate, and gelatin capsule shell).