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.

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 (Clinical Trial)
• Estimated 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
• Actual Study Start Date: September 27, 2023
• Estimated Primary Completion Date: December 2025
• Estimated Study Completion Date: December 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.

Outcome Measures

Primary Outcome Measures :

1. Dose Limiting Toxicities [ Time Frame: From first dose until the end of Cycle 1 (approximately 28 days, up to 42 days). ]
2. 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.
3. 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.

Secondary Outcome Measures :

1. 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).
2. 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).
3. 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).
4. 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).
5. 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).
6. 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).
7. 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.
8. 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.
9. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

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

Locations

United States, Colorado

Colorado Blood Cancer Institute; Recruiting

Denver, Colorado, United States, 80218

Principal Investigator: Marcello Rotta, MD

United States, New York

Roswell Park Cancer Institute; Recruiting

Buffalo, New York, United States, 14263

Principal Investigator: Eunice Wang, MD

United States, Ohio

Cleveland Clinic Foundation; Recruiting

Cleveland, Ohio, United States, 44195

Principal Investigator: Hetty Carraway, MD

The Ohio State University Wexner Medical Center - James Cancer Hospital; Recruiting

Columbus, Ohio, United States, 43210

Principal Investigator: Alice Mims, MD

United States, Oregon

Oncology Associates of Oregon, P.C.; Recruiting

Eugene, Oregon, United States, 97401

Principal Investigator: Luke Fletcher, MD

Oregon Health & Science University - Knight Cancer Institute - Center of Hematologic Malignancies; Recruiting

Portland, Oregon, United States, 97239

Principal Investigator: Elie Traer, MD

United States, Pennsylvania

Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Research Organization; Recruiting

Philadelphia, Pennsylvania, United States, 19107

Principal Investigator: Gina Keiffer, MD

United States, Tennessee

TriStar Bone Marrow Transplant, LLC; Recruiting

Nashville, Tennessee, United States, 37203

Principal Investigator: Steven Strickland, MD

United States, Texas

St. David's South Austin Medical Center; Recruiting

Austin, Texas, United States, 78745

Principal Investigator: Aravind Ramakrishnan, MD

MD Anderson Cancer Center; Recruiting

Houston, Texas, United States, 77030

Principal Investigator: Courtney DiNardo, MD

Sponsors and Collaborators

Schrödinger, Inc.

Investigators

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

More Information

• Responsible Party: Schrödinger, Inc.
• ClinicalTrials.gov Identifier: NCT05961839
• Other Study ID Numbers: SGR-2921-101
• First Posted: July 27, 2023
• Last Update Posted: April 26, 2024
• Last Verified: April 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Schrödinger, Inc.:

MDS; Relapsed or Refractory AML

Additional relevant MeSH terms:

Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Myelodysplastic Syndromes; Syndrome; Disease; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Bone Marrow Diseases; Precancerous Conditions