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

Advanced Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05382936
• Other study ID #: STML-901-0119
• Status: Completed
• Phase: Phase 1
• Start date: March 19, 2021
• Est. completion date: June 30, 2023

Study information

• Verified date: July 2023
• Source: Stemline Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: June 30, 2023
• Est. primary completion date: May 5, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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) 1.5×10?/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.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

Intervention

Drug:
• SL-901
Patients will take study medication daily, with dosage based on their assigned cohort and regimen.

Locations

Country	Name	City	State
United Kingdom	Christie Hospital	Manchester
United Kingdom	Royal Marsden Hospital	Sutton	Surrey

Sponsors (1)

Lead Sponsor	Collaborator
Stemline Therapeutics, Inc.

Country where clinical trial is conducted

United Kingdom, 

References & Publications (7)

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. — View Citation

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. — View Citation

Gatsonis C, Greenhouse JB. Bayesian methods for phase I clinical trials. Stat Med. 1992 Jul;11(10):1377-89. doi: 10.1002/sim.4780111011. — View Citation

Greenwell IB, Ip A, Cohen JB. PI3K Inhibitors: Understanding Toxicity Mechanisms and Management. Oncology (Williston Park). 2017 Nov 15;31(11):821-8. — View Citation

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. — View Citation

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. — View Citation

Storer BE. Design and analysis of phase I clinical trials. Biometrics. 1989 Sep;45(3):925-37. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Characterize the pharmacokinetics (PK) profile of SL-901	Determine the maximum concentration of SL-901 in plasma	Approximately 1 year
Primary	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	Characterize the pharmacodynamics (PD) of SL-901 in blood		Approximately 1 year
Secondary	Assess preliminary clinical activity of SL-901	Determine the objective response rate	Approximately 1 year
Secondary	Characterize the pharmacodynamics (PD) of SL-901 in tissue		Approximately 1 year