Clinical trial NCT05961839: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
High-Risk and Very High-Risk Myelodysplastic Syndromes
Keywords: MDS
Relapsed or Refractory AML
Lead sponsor: Schrödinger, Inc.
Sponsor class: INDUSTRY
First posted: 2023-07-27
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Dose Limiting Toxicities
timeFrame: From first dose until the end of Cycle 1 (approximately 28 days, up to 42 days).
measure: Adverse Events
timeFrame: Throughout the study, up to 26 months.
measure: Electrocardiograms in Singlicate and Triplicate
timeFrame: Throughout the study, up to 26 months.
Secondary outcomes:
measure: SGR-2921 Maximal Plasma Concentration (Cmax)
timeFrame: Throughout the study, up to 26 months.
measure: SGR-2921 Minimum Plasma Concentration (Cmin)
timeFrame: Throughout the study, up to 26 months.
measure: SGR-2921 Time to Maximal Plasma Concentration (tmax)
timeFrame: Throughout the study, up to 26 months.
measure: SGR-2921 Area Under the Concentration Versus Time Curve (AUC)
timeFrame: Throughout the study, up to 26 months.
measure: Composite Complete Remission (CR) Rate for Subjects with AML
timeFrame: Throughout the study, up to 26 months.
measure: Objective Response Rate (ORR) for Subjects with AML
timeFrame: Throughout the study, up to 26 months.
measure: Objective Response Rate (ORR) for Subjects with MDS
timeFrame: Throughout the study, up to 26 months.
measure: Duration of Response (DOR) for Subjects with AML
timeFrame: Throughout the study, up to 26 months.
measure: Duration of Response (DOR) for subjects with MDS
timeFrame: Throughout the study, up to 26 months.
Other outcomes:
Locations:
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Fairway
country: United States
facility: The University of Kansas Clinical Research Center
state: Kansas
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center - James Cancer Hospital
state: Ohio
city: Eugene
country: United States
facility: Oncology Associates of Oregon, P.C.
state: Oregon
city: Portland
country: United States
facility: Oregon Health & Science University - Knight Cancer Institute - Center of Hematologic Malignancies
state: Oregon
city: Philadelphia
country: United States
facility: Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Research Organization
state: Pennsylvania
city: Nashville
country: United States
facility: TriStar Bone Marrow Transplant, LLC
state: Tennessee
city: Austin
country: United States
facility: St. David's South Austin Medical Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Schrödinger, Inc.
name: Daniel Weiss, M.D.
role: STUDY_DIRECTOR
References: