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

• ClinicalTrials.gov Identifier: NCT05961839
• Recruitment Status: Recruiting
• First Posted: July 27, 2023
• Last Update Posted: April 26, 2024
• Sponsor: Schrödinger, Inc.
• Information provided by (Responsible Party): Schrödinger, Inc.

Tracking Information

• First Submitted Date: July 17, 2023
• First Posted Date: July 27, 2023
• Last Update Posted Date: April 26, 2024
• Actual Study Start Date: September 27, 2023
• Estimated Primary Completion Date: December 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 17, 2023)

• Dose Limiting Toxicities [ Time Frame: From first dose until the end of Cycle 1 (approximately 28 days, up to 42 days). ]
• Adverse Events [ Time Frame: 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 [ Time Frame: Throughout the study, up to 26 months. ]
  Uncorrected QT interval, QTcF, PR duration, QRS interval, and RR interval.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 25, 2023)

• SGR-2921 Maximal Plasma Concentration (Cmax) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Throughout the study, up to 26 months. ]
  The percentage of subjects achieving CR and PR.
• Duration of Response (DOR) for Subjects with AML [ Time Frame: 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 [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: July 17, 2023)

• SGR-2921 Maximal Plasma Concentration (Cmax) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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-1505 Area Under the Concentration Versus Time Curve (AUC) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Throughout the study, up to 26 months. ]
  The percentage of subjects achieving CR and PR.
• Duration of Response (DOR) for Subjects with AML [ Time Frame: 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 [ Time Frame: 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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of SGR-2921 in Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome
• 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Acute Myeloid Leukemia
• High-Risk and Very High-Risk Myelodysplastic Syndromes

Intervention

Drug: SGR-2921

SGR-2921 will be administered orally.

Study Arms

• 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.
  Intervention: Drug: SGR-2921
• 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.
  Intervention: Drug: SGR-2921

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 17, 2023): 50
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2025
• Estimated Primary Completion Date: December 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Study Physician; +15032991150; sdgr-trials-group@schrodinger.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05961839
• Other Study ID Numbers: SGR-2921-101
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Schrödinger, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Schrödinger, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Schrödinger, Inc.
• Verification Date: April 2024