Study of the PI3K Inhibitor SL-901 in Patients With Advanced Solid Tumors With Advanced Solid Tumors

Study Overview
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Brief Summary
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Study STML-901-0119 is a dose-escalation study evaluating multiple doses and schedules of orally administered SL-901 in patients with Advanced Solid Tumors.

Detailed Description
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Study STML-901-0119 is a multi-center, open-label, dose-escalation and regimen-finding study aimed to investigate the safety, PK, and PD of SL-901 in patients with advanced solid tumors. Part 1a will take place in up to 5 centers in the United Kingdom and follow a 3+3 dose-escalation design to determine the maximum tolerated dose of SL-901 when administered on both a QD and BID schedule. Eligible patients will be enrolled and receive treatment with SL-901 daily on a 28-day cycle. SL-901 will be administered orally and the dose regimen will depend on the cohort and regimen in which the patient is enrolled. Part 1b will utilize the selected dose from Part 1a, and the clinical activity of SL-901 will be evaluated in patients with advanced solid tumors known to have specific genetic alterations, who may derive benefit from treatment with a phosphoinositide 3-kinase (PI3K) inhibitor.

Official Title
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A Phase 1, Open-label, Dose-escalation Study of the PI3K Inhibitor SL-901 in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: SL-901


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years old or older. Population by study stage: Part 1a: Patients with advanced, metastatic, and/or progressive solid tumors for whom there is no effective standard therapy available. Part 1b: Patients with histologically confirmed, advanced, metastatic, unresectable, and/or progressive solid tumors for whom there is no effective standard therapy available and their PI3K or DNA-PK pathway is deregulated or their tumor genetic profile has been shown to correlate with sensitivity to PI3K and/or DNA-PK inhibition based on clinical and preclinical experience. Specific criteria will be determined based on ongoing experiments and will be introduced in a future protocol amendment. Evaluable or measurable disease. Eastern Cooperative Oncology Group (ECOG) performance status ≤2. Able to take oral medications. If a woman of childbearing potential (WOCBP), the patient has a negative serum or urine pregnancy test within 1 week before Cycle 1, Day 1 (C1D1). Refer to Section 8.1.3 for further practical information about contraception. The patient (either male or female) agrees to use acceptable contraceptive methods for the duration of time in the study, and to continue to use acceptable contraceptive methods for 1 month after the last dose of SL-901. Refer to Section 8.1.3 for further practical information about contraception. Able to provide written informed consent. Willing to provide consent for biomarker analysis of existing paraffin-embedded tumor samples. Exclusion Criteria: Received an investigational anticancer drug within 4 weeks of the first planned SL-901 dose. Received major surgery, radiotherapy, or immunotherapy within 4 weeks of C1D1. Localized palliative radiotherapy is permitted for symptom control. Received chemotherapy regimens with delayed toxicity within 4 weeks (6 weeks for prior nitrosourea or mitomycin C) of C1D1. Received chemotherapy regimens given continuously or on a weekly basis which have limited potential for delayed toxicity within 2 weeks of C1D1. Clinically significant, unresolved toxicity from previous anticancer therapy ≥Grade 2 (except alopecia), as determined by the Investigator using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0. Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of drugs. Left ventricular ejection fraction <50%. Corrected QT interval (based on Fridericia's formula) >450 msec. Type 1 or 2 diabetes mellitus requiring medication. (In Part 1b, patients with type 2 diabetes mellitus controlled by medication, as indicated by a glycated hemoglobin of ≤7.5% are eligible.) Known active human immunodeficiency virus, hepatitis B, or hepatitis C infection. Ongoing systemic bacterial, fungal, or viral infection. History of interstitial pneumonitis. Absolute neutrophil count (ANC) 1.5×10⁹/L. Hemoglobin <10 g/dL. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5x the upper limit of normal (ULN). Known hypersensitivity or allergy to the active ingredient or excipients of SL-901. Breast-feeding females.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be assigned to the QD or BID regimen based on cohort assignment.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: QD Regimen<br>Patients in the QD regimen will take study medication once daily. | Drug: SL-901<br>* Patients will take study medication daily, with dosage based on their assigned cohort and regimen.<br>|
| Experimental: BID Regimen<br>Patients in the BID regimen will take study medication twice daily. | Drug: SL-901<br>* Patients will take study medication daily, with dosage based on their assigned cohort and regimen.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose | Identify the maximum tolerated dose (or maximum tested dose if no maximum tolerated dose is identified) of SL-901 to be utilized. | Approximately 1 year | 
| Identify an appropriate dosing regimen for further investigation of SL-901 | Identify if the QD or BID dosing regimen will be utilized | Approximately 1 year | 
| Characterize the pharmacokinetics (PK) profile of SL-901 | Determine the maximum concentration of SL-901 in plasma | Approximately 1 year | 
| Perform initial assessment of the safety profile of SL-901 | The percentage of patients experiencing treatment-related and treatment-emergent adverse events | Approximately 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterize the pharmacodynamics (PD) of SL-901 in blood |  | Approximately 1 year | 
| Assess preliminary clinical activity of SL-901 | Determine the objective response rate | Approximately 1 year | 
| Characterize the pharmacodynamics (PD) of SL-901 in tissue |  | Approximately 1 year |