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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Acute Myeloid Leukemia, High-Risk and Very High-Risk Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: SGR-2921


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation in the Absence of Specific Azole Antifungal Treatments<br>Up to 9 dose levels will be evaluated in subjects not receiving specific azole antifungal treatment. | Drug: SGR-2921<br>* SGR-2921 will be administered orally.<br>|
| Experimental: Dose Escalation in the Presence of Specific Azole Antifungal Treatments<br>Up to 9 dose levels will be evaluated in subjects receiving specific azole antifungal treatment. | Drug: SGR-2921<br>* SGR-2921 will be administered orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicities |  | From first dose until the end of Cycle 1 (approximately 28 days, up to 42 days). | 
| 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. | 
| Electrocardiograms in Singlicate and Triplicate | Uncorrected QT interval, QTcF, PR duration, QRS interval, and RR interval. | Throughout the study, up to 26 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 
| 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. | 
| 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. | 
| 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. | 
| 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. | 
| 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. | 
| Objective Response Rate (ORR) for Subjects with MDS | The percentage of subjects achieving CR and PR. | Throughout the study, up to 26 months. | 
| 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. | 
| 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MDS, Relapsed or Refractory AML