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

Sponsor

Schrödinger, Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05961839

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia High-Risk and Very High-Risk Myelodysplastic Syndromes	Drug: SGR-2921	Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Oct 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2025

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Dose Escalation in the Absence of Specific Azole Antifungal Treatments

Up to 9 dose levels will be evaluated in subjects not receiving specific azole antifungal treatment.

Drug: SGR-2921

SGR-2921 will be administered orally.

Experimental: Dose Escalation in the Presence of Specific Azole Antifungal Treatments

Up to 9 dose levels will be evaluated in subjects receiving specific azole antifungal treatment.

Drug: SGR-2921

SGR-2921 will be administered orally.

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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).
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).
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).
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 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.