Study of SGR-2921 in Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome

Acute Myeloid Leukemia Clinical Trial

Official title:

A First-In-Human, Phase 1, Dose Escalation Study of SGR-2921 as Monotherapy In Subjects With Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05961839
• Other study ID #: SGR-2921-101
• Status: Recruiting
• Phase: Phase 1
• Start date: September 27, 2023
• Est. completion date: December 2025

Study information

• Verified date: June 2024
• Source: Schrödinger, Inc.
• Contact: Study Physician
• Phone: +15032991150
• Email: sdgr-trials-group[@]schrodinger.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate safety and tolerability and to determine the maximum tolerated dose (MTD) and/or recommended dose (RD) of SGR-2921.

Description:

This is a study of SGR-2921, an oral, small molecule inhibitor of cell division cycle 7-related protein kinase (CDC7), in subjects with Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD), maximum tolerated dose (MTD) and/or recommended dose (RD) of SGR-2921.

Exploratory cohorts may evaluate additional PK, PD, preliminary anti-tumor activity, and safety to establish the SGR-2921 RD. A planned amendment will evaluate SGR-2921 in combination with other approved AML/MDS treatments such as hypomethylating agents (HMA), BCL2 inhibitors, IDH inhibitors or FLT3 inhibitors, in patients with AML and/or MDS.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• = 18 years of age.

• Life expectancy = 8 weeks.

• Confirmed diagnosis of R/R AML or High Risk (HR) and Very High Risk (VHR) MDS.

• Eastern Cooperative Oncology Group (ECOG) performance status = 2.

Exclusion Criteria:

• Active malignancies within two years prior to the first dose, or requiring ongoing treatment, not related to AML or MDS.

• Clinical evidence of central nervous system (CNS) or pulmonary leukostasis, = Grade 3 disseminated intravascular coagulation, or active CNS leukemia.

• Use of experimental drug, or therapy, or anti-cancer therapy within 14 days or 5 half-lives of the first dose of study drug.

• QT interval corrected for heart rate per Fridericia's formula =470 msec during screening ECG.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• SGR-2921
SGR-2921 will be administered orally.

Locations

Country	Name	City	State
United States	St. David's South Austin Medical Center	Austin	Texas
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	The Ohio State University Wexner Medical Center - James Cancer Hospital	Columbus	Ohio
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	Oncology Associates of Oregon, P.C.	Eugene	Oregon
United States	MD Anderson Cancer Center	Houston	Texas
United States	TriStar Bone Marrow Transplant, LLC	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Research Organization	Philadelphia	Pennsylvania
United States	Oregon Health & Science University - Knight Cancer Institute - Center of Hematologic Malignancies	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Schrödinger, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Limiting Toxicities		From first dose until the end of Cycle 1 (approximately 28 days, up to 42 days).
Primary	Adverse Events	Incidence, nature, and severity of adverse events (AEs) as assessed by the NCI CTCAE v5.0.	Throughout the study, up to 26 months.
Primary	Electrocardiograms in Singlicate and Triplicate	Uncorrected QT interval, QTcF, PR duration, QRS interval, and RR interval.	Throughout the study, up to 26 months.
Secondary	SGR-2921 Maximal Plasma Concentration (Cmax)	Concentrations of SGR-2921 in plasma are measured at various timepoints following its administration to calculate typical exposure/PK parameters, including, but not limited to, the maximal plasma concentration (Cmax).	Throughout the study, up to 26 months.
Secondary	SGR-2921 Minimum Plasma Concentration (Cmin)	Concentrations of SGR-2921 in plasma are measured at various timepoints following its administration to calculate typical exposure/PK parameters, including, but not limited to, the minimum plasma concentration (Cmin).	Throughout the study, up to 26 months.
Secondary	SGR-2921 Time to Maximal Plasma Concentration (tmax)	Concentrations of SGR-2921 in plasma are measured at various timepoints following its administration to calculate typical exposure/PK parameters, including, but not limited to, the time to maximal plasma concentration (tmax).	Throughout the study, up to 26 months.
Secondary	SGR-2921 Area Under the Concentration Versus Time Curve (AUC)	Concentrations of SGR-2921 in plasma are measured at various timepoints following its administration to calculate typical exposure/PK parameters, including, but not limited to, the area under the concentration versus time curve (AUC).	Throughout the study, up to 26 months.
Secondary	Composite Complete Remission (CR) Rate for Subjects with AML	The percentage of subjects with CR, CR with Partial Hematologic Recovery (CRh), and CR with Incomplete Blood Count Recovery (CRi).	Throughout the study, up to 26 months.
Secondary	Objective Response Rate (ORR) for Subjects with AML	The percentage of subjects achieving CR, CRh, CRi, morphologic leukemia-free state (MLFS) and Partial Response (PR).	Throughout the study, up to 26 months.
Secondary	Objective Response Rate (ORR) for Subjects with MDS	The percentage of subjects achieving CR and PR.	Throughout the study, up to 26 months.
Secondary	Duration of Response (DOR) for Subjects with AML	The time from first response (CR, CRh, CRi, MLFS, or PR) to the date of initial objectively documented progression or death due to any cause, whichever occurs first.	Throughout the study, up to 26 months.
Secondary	Duration of Response (DOR) for subjects with MDS	The time from first response (CR or PR) to the date of initial objectively documented progression or death due to any cause, whichever occurs first.	Throughout the study, up to 26 months.