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

Summary

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.

Eligibility

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

Conditions2

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