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

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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: SL-901

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Mary Ann Samparani; Phone Number: (646)731-2146; Email: msamparani@stemline.com

Study Locations

• United Kingdom
  • Manchester, United Kingdom, M20 4BX
    • Christie Hospital
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • Royal Marsden Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 18 years old or older.

2. Population by study stage:

   1. Part 1a: Patients with advanced, metastatic, and/or progressive solid tumors for whom there is no effective standard therapy available.
   2. 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.
3. Evaluable or measurable disease.
4. Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
5. Able to take oral medications.
6. 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.
7. 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.
8. Able to provide written informed consent.
9. Willing to provide consent for biomarker analysis of existing paraffin-embedded tumor samples.

Exclusion Criteria:

1. Received an investigational anticancer drug within 4 weeks of the first planned SL-901 dose.
2. Received major surgery, radiotherapy, or immunotherapy within 4 weeks of C1D1. Localized palliative radiotherapy is permitted for symptom control.
3. Received chemotherapy regimens with delayed toxicity within 4 weeks (6 weeks for prior nitrosourea or mitomycin C) of C1D1.
4. Received chemotherapy regimens given continuously or on a weekly basis which have limited potential for delayed toxicity within 2 weeks of C1D1.
5. 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.
6. Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of drugs.
7. Left ventricular ejection fraction <50%.
8. Corrected QT interval (based on Fridericia's formula) >450 msec.
9. 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.)
10. Known active human immunodeficiency virus, hepatitis B, or hepatitis C infection.
11. Ongoing systemic bacterial, fungal, or viral infection.
12. History of interstitial pneumonitis.
13. Absolute neutrophil count (ANC) 1.5×10⁹/L.
14. Hemoglobin <10 g/dL.
15. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5x the upper limit of normal (ULN).
16. Known hypersensitivity or allergy to the active ingredient or excipients of SL-901.
17. Breast-feeding females.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Stemline Therapeutics, Inc.

Publications and helpful links

General Publications

• Storer BE. Design and analysis of phase I clinical trials. Biometrics. 1989 Sep;45(3):925-37.
• Ahn C. An evaluation of phase I cancer clinical trial designs. Stat Med. 1998 Jul 30;17(14):1537-49. doi: 10.1002/(sici)1097-0258(19980730)17:143.0.co;2-f.
• Gatsonis C, Greenhouse JB. Bayesian methods for phase I clinical trials. Stat Med. 1992 Jul;11(10):1377-89. doi: 10.1002/sim.4780111011.
• Courtney KD, Corcoran RB, Engelman JA. The PI3K pathway as drug target in human cancer. J Clin Oncol. 2010 Feb 20;28(6):1075-83. doi: 10.1200/JCO.2009.25.3641. Epub 2010 Jan 19.
• Greenwell IB, Ip A, Cohen JB. PI3K Inhibitors: Understanding Toxicity Mechanisms and Management. Oncology (Williston Park). 2017 Nov 15;31(11):821-8.
• Krause G, Hassenruck F, Hallek M. Copanlisib for treatment of B-cell malignancies: the development of a PI3K inhibitor with considerable differences to idelalisib. Drug Des Devel Ther. 2018 Aug 21;12:2577-2590. doi: 10.2147/DDDT.S142406. eCollection 2018.
• Liu P, Cheng H, Roberts TM, Zhao JJ. Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009 Aug;8(8):627-44. doi: 10.1038/nrd2926.

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2021
• Primary Completion (Actual): May 5, 2023
• Study Completion (Actual): June 30, 2023

Study Registration Dates

• First Submitted: October 21, 2021
• First Submitted That Met QC Criteria: May 16, 2022
• First Posted (Actual): May 19, 2022

Study Record Updates

• Last Update Posted (Actual): July 12, 2023
• Last Update Submitted That Met QC Criteria: July 10, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: STML-901-0119

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: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No