This is an open-label, dose-escalation, multi-center phase 1 study evaluating the safety, tolerability, and pharmacokinetics (PK) of SR-8541A administered orally as a monotherapy or in combination with an immune checkpoint inhibitor (ICI) in subjects with solid tumors.
SR-8541A, an ENPP1 inhibitor, will be administered orally as a monotherapy to assess safety, tolerability, and pharmacokinetics (PK) in subjects with advanced/metastatic solid tumors. Subjects eligible for treatment include those whose disease is refractory to standard therapeutic options, or for which there are no standard therapeutic options available. All enrolled patients will orally administer SR-8541A daily. Treatment may continue until the subject's disease worsens or another treatment discontinuation criterion is met. The combination part will only commence once the SRC has deemed it safe to proceed and a SR-8541A dose from the dose escalation part is selected as the RP2D. The ICI will be either nivolumab or pembrolizumab and dosing will be per SOC. Both investigational products will start on C1D1. Treatment with ICI may be continued if SR-8541A is discontinued and treatment with SR-8541A may be continued after ICI is discontinued. Approximately 10 subjects will be enrolled.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
25
orally administered ENPP1 inhibitor
The ICI will be either nivolumab or pembrolizumab.
Scientia Clinical Research Ltd
Randwick, New South Wales, Australia
RECRUITINGMonash Health
Clayton, Victoria, Australia
RECRUITINGPeninsula & South Eastern Haematology & Oncology Group
Frankston, Victoria, Australia
RECRUITINGFrequency and severity of Adverse Events
Adverse events will be graded according to CTCAE v5.0.
Time frame: From first dose of study drug through 30 days following the last dose of study treatment
Recommended Phase 2 Dose (RP2D) of SR-8541A
Based on evaluation of Dose Limiting Toxicities (DLT)
Time frame: From first dose of study drug through 28 days following the first dose of study treatment
Maximum plasma concentration (Cmax)
Cmax measured in ng/mL
Time frame: From first dose of study drug through 28 days following the first dose of study treatment
Area under the curve from zero up to time t (AUC0-t)
AUC0-t measured in ng.h/mL
Time frame: From first dose of study drug through 28 days following the first dose of study treatment
Area under the concentration time curve from time 0 extrapolated to infinity (AUC0-inf)
AUC0-inf measured in ng.h/mL
Time frame: From first dose of study drug through 28 days following the first dose of study treatment
Maximal time for peak concentration (Tmax)
Tmax measured in h
Time frame: From first dose of study drug through 28 days following the first dose of study treatment
Terminal phase rate constant (λz)
λz measured in 1/h
Time frame: From first dose of study drug through 28 days following the first dose of study treatment
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Half-life (t1/2)
t1/2 measured in h
Time frame: From first dose of study drug through 28 days following the first dose of study treatment
Overall Response Rate
Defined as the proportion of subjects in the efficacy population who achieve a radiographic investigator-assessed confirmed complete response (CR)/immune CR (iCR) or partial response (PR)/immune PR (iPR) per RECIST v1.1 or immune Response Evaluation Criteria in Solid Tumors (iRECIST) v1.0
Time frame: From first dose of study drug through 2 years following first dose
Progression Free Survival
Defined as the time from start of treatment to the first documentation of progressive disease (PD) or death from any cause, whichever occurs first
Time frame: From first dose of study drug through 2 years following first dose
Duration of Response
Defined as the time from the date a response of PR or better was first recorded to the date on which PD was first noted or the date of death due to any cause
Time frame: From first dose of study drug through 2 years following first dose
Disease Control Rate
Defined as the proportion of subjects who achieve an investigator-assessed confirmed CR/iCR, PR/iPR, or Stable Disease (SD)/immune SD (iSD) at 16 weeks per RECIST v1.1 or iRECIST v1.0
Time frame: From first dose of study drug through 2 years following first dose
Overall Survival
Defined as the time from the start of treatment until death due to any cause
Time frame: From first dose of study drug through 2 years following first dose