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

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

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.

Study Overview

• Status: Terminated
• Conditions: Acute Myeloid Leukemia; High-Risk and Very High-Risk Myelodysplastic Syndromes
• Intervention / Treatment: Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute
  • Kansas
    • Fairway, Kansas, United States, 66205
      • The University of Kansas Clinical Research Center
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center - James Cancer Hospital
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Oncology Associates of Oregon, P.C.
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University - Knight Cancer Institute - Center of Hematologic Malignancies
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Research Organization
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • TriStar Bone Marrow Transplant, LLC
  • Texas
    • Austin, Texas, United States, 78745
      • St. David's South Austin Medical Center
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Schrödinger, Inc.
• Investigators: Study Director: Daniel Weiss, M.D., Schrödinger, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2023
• Primary Completion (Actual): August 14, 2025
• Study Completion (Actual): September 9, 2025

Study Registration Dates

• First Submitted: July 17, 2023
• First Submitted That Met QC Criteria: July 17, 2023
• First Posted (Actual): July 27, 2023

Study Record Updates

• Last Update Posted (Actual): September 22, 2025
• Last Update Submitted That Met QC Criteria: September 17, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: MDS; Relapsed or Refractory AML
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Leukemia, Myeloid, Acute
• Other Study ID Numbers: SGR-2921-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No