Acute Myeloid Leukemia, High-Risk and Very High-Risk Myelodysplastic Syndromes
Conditions
Keywords
MDS, Relapsed or Refractory AML
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.
Interventions
DRUGSGR-2921
SGR-2921 will be administered orally.
Sponsors
Schrödinger, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Electrocardiograms in Singlicate and Triplicate | Throughout the study, up to 26 months. | Uncorrected QT interval, QTcF, PR duration, QRS interval, and RR interval. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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). |
| 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). |
| 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. |
| 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. |
| Objective Response Rate (ORR) for Subjects with MDS | Throughout the study, up to 26 months. | The percentage of subjects achieving CR and PR. |
| 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). |
| 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). |
Countries
United States
Outcome results
None listed