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

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

This is an open-label, dose-escalation, multi-center phase 1 study evaluating the safety, tolerability, and pharmacokinetics (PK) of SR-8541A, an ENPP1 inhibitor, administered orally as a monotherapy in subjects with solid tumors.

Study Overview

• Status: Recruiting
• Conditions: Advanced / Metastatic Solid Tumor
• Intervention / Treatment: Drug: SR-8541A

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.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Monil Shah; Phone Number: 201-978-8032; Email: mshah@stingraytx.com

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Recruiting
      • Scientia Clinical Research Ltd
      • Contact: Charlotte Lemech
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Not yet recruiting
      • Monash Health
      • Contact: Amy Body
    • Frankston, Victoria, Australia, 3199
      • Recruiting
      • Peninsula & South Eastern Haematology & Oncology Group
      • Contact: Vinod Ganju

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

Exclusion Criteria:

1. Primary central nervous system (CNS) tumor
2. Prior systemic anti-cancer treatment including other investigational agents, surgery, or radiation within 28 days or 5 half-lives, whichever is less
3. Continuous systemic treatment with either corticosteroids (>10 milligram [mg] daily prednisone equivalents) or other immunosuppressive medications within 28 days
4. Active autoimmune disease that has required systemic treatment in past 2 years
5. 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
6. Troponin I > ULN
7. Blood pressure (BP) - Systolic < 95 mmHg or > 160 mmHg or diastolic > 100 mmHg
8. Resting heart rate (HR) > 100 beats per minute (BPM)
9. Corrected QT interval by Fridericia (QTcF) ≥ 470 ms
10. Left Ventricular Ejection Fraction (LVEF) < 50%
11. Symptomatic uncontrolled CNS disease requiring treatment with steroids or anti-seizure medications within 2 months
12. Leptomeningeal disease
13. 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
14. Bleeding diathesis due to underlying medical condition or anticoagulation medication which is unable to be promptly reversed by medical treatment
15. Prior additional malignancy that is progressing or has received treatment the previous 3 years
16. Active infection requiring systemic treatment
17. 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
18. Major surgery within 28 days prior to Day 1 and/or minor surgery (excluding biopsy) within 7 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SR-8541A Monotherapy; SR-8541A will be orally administered.	Drug: SR-8541A; orally administered ENPP1 inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency and severity of Adverse Events	Adverse events will be graded according to CTCAE v5.0.	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)	From first dose of study drug through 28 days following the first dose of study treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum plasma concentration (Cmax)	Cmax measured in ng/mL	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	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	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	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	From first dose of study drug through 28 days following the first dose of study treatment
Half-life (t1/2)	t1/2 measured in h	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	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	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	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	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	From first dose of study drug through 2 years following first dose

Collaborators and Investigators

• Sponsor: Stingray Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2023
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: September 23, 2023
• First Submitted That Met QC Criteria: September 23, 2023
• First Posted (Actual): October 2, 2023

Study Record Updates

• Last Update Posted (Actual): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 21, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Refractory; Solid Tumors; Relapsing
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: StingrayTx

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No