Study of SGR-2921 in Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome
- Conditions
- High-Risk and Very High-Risk Myelodysplastic SyndromesAcute Myeloid Leukemia
- Interventions
- Registration Number
- NCT05961839
- Lead Sponsor
- Schrödinger, Inc.
- Brief 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.
- Detailed 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 & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 50
- ≥ 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation in the Absence of Specific Azole Antifungal Treatments SGR-2921 Up to 9 dose levels will be evaluated in subjects not receiving specific azole antifungal treatment. Dose Escalation in the Presence of Specific Azole Antifungal Treatments SGR-2921 Up to 9 dose levels will be evaluated in subjects receiving specific azole antifungal treatment.
- Primary Outcome Measures
Name Time Method Electrocardiograms in Singlicate and Triplicate Throughout the study, up to 26 months. Uncorrected QT interval, QTcF, PR duration, QRS interval, and RR interval.
Dose Limiting Toxicities From first dose until the end of Cycle 1 (approximately 28 days, up to 42 days). Adverse Events Throughout the study, up to 26 months. Incidence, nature, and severity of adverse events (AEs) as assessed by the NCI CTCAE v5.0.
- Secondary Outcome Measures
Name Time Method SGR-2921 Area Under the Concentration Versus Time Curve (AUC) Throughout the study, up to 26 months. 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).
SGR-2921 Maximal Plasma Concentration (Cmax) Throughout the study, up to 26 months. 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).
SGR-2921 Minimum Plasma Concentration (Cmin) Throughout the study, up to 26 months. 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).
Duration of Response (DOR) for Subjects with AML Throughout the study, up to 26 months. 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.
SGR-2921 Time to Maximal Plasma Concentration (tmax) Throughout the study, up to 26 months. 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).
Composite Complete Remission (CR) Rate for Subjects with AML Throughout the study, up to 26 months. The percentage of subjects with CR, CR with Partial Hematologic Recovery (CRh), and CR with Incomplete Blood Count Recovery (CRi).
Objective Response Rate (ORR) for Subjects with AML Throughout the study, up to 26 months. The percentage of subjects achieving CR, CRh, CRi, morphologic leukemia-free state (MLFS) and Partial Response (PR).
Objective Response Rate (ORR) for Subjects with MDS Throughout the study, up to 26 months. The percentage of subjects achieving CR and PR.
Duration of Response (DOR) for subjects with MDS Throughout the study, up to 26 months. 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.
Trial Locations
- Locations (12)
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
TriStar Bone Marrow Transplant, LLC
🇺🇸Nashville, Tennessee, United States
The Ohio State University Wexner Medical Center - James Cancer Hospital
🇺🇸Columbus, Ohio, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Oncology Associates of Oregon, P.C.
🇺🇸Eugene, Oregon, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Colorado Blood Cancer Institute
🇺🇸Denver, Colorado, United States
Oregon Health & Science University - Knight Cancer Institute - Center of Hematologic Malignancies
🇺🇸Portland, Oregon, United States
The University of Kansas Clinical Research Center
🇺🇸Fairway, Kansas, United States
Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Research Organization
🇺🇸Philadelphia, Pennsylvania, United States
St. David's South Austin Medical Center
🇺🇸Austin, Texas, United States