Clinical Trials /

Safety Study of SLC-391 in Subjects With Solid Tumors

NCT03990454

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Safety Study of SLC-391 in Subjects With Solid Tumors
  • Official Title: A Phase 1, Open-label, Dose-escalation, and Dose-expansion Study of the Safety and Pharmacokinetics of the AXL Inhibitor SLC-391 Administered Orally to Subjects With Solid Tumours

Clinical Trial IDs

  • ORG STUDY ID: SLC-391-101
  • NCT ID: NCT03990454

Conditions

  • Solid Tumor

Interventions

DrugSynonymsArms
SLC-391Dose escalation/expansion

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Dose escalation/expansionExperimentalThe starting dose will be 25 mg/day and subsequent doses will be determined after an internal review by Data Review Committee of all available safety, PK and PD data from the minimum required number of subjects who complete cycle 1. All dose-escalation decisions and the rationale for progressing to the next cohort will be documented. A subject may continue treatment with SLC-391 in 21-day cycles until the treatment discontinuation criteria are met. Subjects with certain tumour types (e.g., NSCLC or ovarian) may be enrolled in expansion cohorts of up to 12 subjects at doses less than or equal to the MTD to better characterise the activity and safety of SLC-391 and define the Recommended Phase 2 Dose (RP2D) dose.
  • SLC-391

Eligibility Criteria

        Inclusion Criteria:

          -  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
             (RECIST) 1.1.

          -  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
             administered.

          -  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.

        Exclusion Criteria:

          -  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
             (Mycobacterium 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).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants with Adverse Events (AEs) as assessed by NCI-CTCAE v5.0
Time Frame:2 years
Safety Issue:
Description:To assess AEs as criteria of safety of oral SLC-391

Secondary Outcome Measures

Measure:Area under the plasma concentration versus time curve (AUC) of SLC-391
Time Frame:Day 1 predose through to Day 21 post-final dose
Safety Issue:
Description:Changes in AUC over time in subjects taking SLC-391 once daily.
Measure:Maximum Observed Plasma Concentration (Cmax)
Time Frame:Day 1 predose through to Day 21 post-final dose
Safety Issue:
Description:Cmax is the maximum observed plasma concentration in ng/mL
Measure:Time to the Maximum Observed Plasma Concentration (Tmax)
Time Frame:Day 1 predose through to Day 21 post-final dose
Safety Issue:
Description:Tmax is the time in hours to reach Cmax following dosing
Measure:Terminal elimination half-life (t1/2)
Time Frame:Day 1 predose through to Day 21 post-final dose
Safety Issue:
Description:The time in hours required for the plasma level of the study drug to decrease by one-half during the terminal elimination phase
Measure:Recommended Dose of SLC-391 for future trials
Time Frame:2 years
Safety Issue:
Description:Determine the recommended phase 2 dose (RP2D) of SLC-391
Measure:Preliminary efficacy of SLC-391
Time Frame:2 years
Safety Issue:
Description:Determine tumour response defined by the Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 to SLC-391

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:SignalChem Lifesciences Corporation

Trial Keywords

  • AXL Inhibitor
  • Solid Tumor

Last Updated

October 28, 2019