A Study of SR-8541A (ENPPI Inhibitor) in Advanced/Metastatic Solid Tumors

Official title

Phase 1, Dose Escalation, Safety, Tolerability, and Pharmacokinetic Study of SR-8541A (ENPP1 Inhibitor) Administered Orally as Monotherapy or in Combination With Checkpoint Inhibitors in Subjects With Advanced/Metastatic Solid Tumors

Overview

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.

Detailed description

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.

Interventions

• Drug SR-8541A
  orally administered ENPP1 inhibitor
• Drug Immune checkpoint inhibitor (ICI)
  The ICI will be either nivolumab or pembrolizumab.

Primary outcome measures

• Frequency and severity of Adverse Events [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 [Time frame: From first dose of study drug through 28 days following the first dose of study treatment]

Secondary outcome measures (11)

• Maximum plasma concentration (Cmax) [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) [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) [Time frame: From first dose of study drug through 28 days following the first dose of study treatment]
• Maximal time for peak concentration (Tmax) [Time frame: From first dose of study drug through 28 days following the first dose of study treatment]
• Terminal phase rate constant (λz) [Time frame: From first dose of study drug through 28 days following the first dose of study treatment]
• Half-life (t1/2) [Time frame: From first dose of study drug through 28 days following the first dose of study treatment]
• Overall Response Rate [Time frame: From first dose of study drug through 2 years following first dose]
• Progression Free Survival [Time frame: From first dose of study drug through 2 years following first dose]
• Duration of Response [Time frame: From first dose of study drug through 2 years following first dose]
• Disease Control Rate [Time frame: From first dose of study drug through 2 years following first dose]
• Overall Survival [Time frame: From first dose of study drug through 2 years following first dose]

Eligibility criteria

Inclusion criteria

• Life expectancy of at least 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1
• Histopathologically/cytologically confirmed advanced solid tumor, which is refractory to standard therapeutic options, or for which there are no standard therapeutic options.
• Measurable disease per RECIST v1.1
• Willing to provide archival or fresh tumor tissue during screening (required) and post-treatment (optional)
• Adequate hematologic, renal and hepatic function

Exclusion criteria

• Primary central nervous system (CNS) tumor
• Prior systemic anti-cancer treatment including other investigational agents, surgery, or radiation within 28 days or 5 half-lives, whichever is less
• Continuous systemic treatment with either corticosteroids (>10 milligram \[mg\] daily prednisone equivalents) or other immunosuppressive medications within 28 days
• Active autoimmune disease that has required systemic treatment in past 2 years
• History of documented congestive heart failure (New York Heart Association \[NYHA\] class II - IV); unstable angina; poorly controlled hypertension; clinically significant valvular heart disease; high-risk uncontrolled arrhythmias (including sustained ventricular tachycardia); myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack within the last 6 months, or Canadian Cardiovascular Society angina class > 2
• Troponin I > ULN
• Blood pressure (BP) - Systolic < 95 mmHg or > 160 mmHg or diastolic > 100 mmHg
• Resting heart rate (HR) > 100 beats per minute (BPM)
• Corrected QT interval by Fridericia (QTcF) ≥ 470 ms
• Left Ventricular Ejection Fraction (LVEF) < 50%
• Symptomatic uncontrolled CNS disease requiring treatment with steroids or anti-seizure medications within 2 months
• Leptomeningeal disease
• Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for at least 8 weeks
• Bleeding diathesis due to underlying medical condition or anticoagulation medication which is unable to be promptly reversed by medical treatment
• Prior additional malignancy that is progressing or has received treatment the previous 3 years
• Active infection requiring systemic treatment
• Positive for human immunodeficiency virus (HIV) (HIV antibodies) or active hepatitis B (e.g., HbsAg reactive) or active hepatitis C (e.g., HCV ribonucleic acid \[RNA\] qualitative) infection with detectable viral load
• Major surgery within 28 days prior to Day 1 and/or minor surgery (excluding biopsy) within 7 days

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Australia · 3 centers

• Scientia Clinical Research Ltd — Randwick
• Monash Health — Clayton
• Peninsula & South Eastern Haematology & Oncology Group — Frankston

Identifiers

NCT: NCT06063681 · StingrayTx

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗