Safety Study of SLC-391 in Subjects With Solid Tumors
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|ClinicalTrials.gov Identifier: NCT03990454|
Recruitment Status : Not yet recruiting
First Posted : June 19, 2019
Last Update Posted : August 2, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Solid Tumor||Drug: SLC-391||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||
The study will employ a 3+3 dose-escalation design. Cohorts (same dose level) of 3 to 6 evaluable subjects will participate in a dose-escalation scheme in which the dose of SLC-391 will be increased in each consecutive cohort. Evaluation of a cohort of ≥ 3 subjects that have completed a 21-day cycle (cycle 1) is required prior to defining a new SLC-391 dose and schedule for the next cohort. Dose-escalation decisions by the Data Review Committee will take into account all available data including PK/pharmacodynamic data and the safety profile of prior cohorts. Based on all available emerging data, alternative dosing schedules, frequency, or dose reductions may be considered.
Subjects with certain tumour types (eg, nonsmall cell lung cancer, ovarian) may be enrolled in expansion cohorts (≤ 12 subjects) at doses less than or equal to Maximum Tolerated Dose (MTD) in order to better characterise the antitumour activity and safety of SLC-391 and to define the Recommended Phase 2 Dose dose.
|Masking:||None (Open Label)|
|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|
|Estimated Study Start Date :||September 2019|
|Estimated Primary Completion Date :||August 1, 2020|
|Estimated Study Completion Date :||August 1, 2020|
Experimental: Dose escalation/expansion
The 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 is an AXL inhibitor
- Number of Participants with Adverse Events (AEs) as assessed by NCI-CTCAE v5.0 [ Time Frame: 2 years ]To assess AEs as criteria of safety of oral SLC-391
- Maximum Tolerated Dose of SLC-391 [ Time Frame: 21 days ]To determine the maximum tolerated dose (MTD) of SLC-391
- Area under the plasma concentration versus time curve (AUC) of SLC-391 [ Time Frame: Day 1 predose through to Day 21 post-final dose ]Changes in AUC over time in subjects taking SLC-391 once daily.
- Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Day 1 predose through to Day 21 post-final dose ]Cmax is the maximum observed plasma concentration in ng/mL
- Time to the Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Day 1 predose through to Day 21 post-final dose ]Tmax is the time in hours to reach Cmax following dosing
- Terminal elimination half-life (t1/2) [ Time Frame: Day 1 predose through to Day 21 post-final dose ]The time in hours required for the plasma level of the study drug to decrease by one-half during the terminal elimination phase
- Recommended Dose of SLC-391 for future trials [ Time Frame: 2 years ]Determine the recommended phase 2 dose (RP2D) of SLC-391
- Preliminary efficacy of SLC-391 [ Time Frame: 2 years ]Determine tumour response defined by the Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 to SLC-391
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03990454
|Contact: Zaihui Zhang, PhD||1-604-232-4600 ext firstname.lastname@example.org|
|Contact: Madhu Singh, PhDemail@example.com|
|Juravinski Cancer Centre||Not yet recruiting|
|Hamilton, Ontario, Canada, L8V 5C2|
|Contact: Yvonne Kirndale|
|Principal Investigator: Sebastien Hotte, MD|
|The Ottawa Hospital Cancer Center||Not yet recruiting|
|Ottawa, Ontario, Canada, K1H 8L6|
|Contact: Lena McAleer|
|Principal Investigator: Scott Laurie, MD|
|Princess Margaret Cancer Centre||Not yet recruiting|
|Toronto, Ontario, Canada, M5G 2M9|
|Contact: Tuhina Paul|
|Principal Investigator: Natasha Leighl, MD|
|Study Director:||Zaihui Zhang, PhD||SignalChem Lifesciences Corporation|