Phase 1 Study of Shattuck Labs (SL)-172154 in Subjects with MDS or AML

Phase 1

Active, not recruiting

• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndromes
• Interventions: Drug: SL-172154

• Registration Number: NCT05275439
• Lead Sponsor: Shattuck Labs, Inc.

Brief Summary

SL03-Old Hundred(OHD)-104 is designed as a Phase 1a/1b open label, trial to evaluate the safety, pharmacokinetics (PK), pharmacodynamic (PD), and preliminary efficacy of SL-172154 monotherapy as well as in combination with azacitidine or in combination with Azacitidine and Venetoclax.

Detailed Description

This Phase 1a/1b study is an open label, multicenter trial in subjects with higher-risk (i.e., intermediate, high or very high risk by IPSS-R) MDS or AML. The study is designed to evaluate the safety, PK, pharmacodynamic effects, and preliminary anti tumor activity of SL-172154 monotherapy and SL-1712154 administered with either Azacitidine or Azacitidine and Venetoclax. Subjects will receive SL-172154 as monotherapy or administered with Azacitidine with or without Venetoclax until documented disease progression, unacceptable toxicity or intolerance, withdrawal of consent, or the subject meets other criteria for discontinuation (whichever occurs first).

Part D: Safety and efficacy will be further explored in Part D. Approximately 60 subjects with previously untreated higher-risk MDS will be randomized equally into 3 groups: 3.0 mg/kg SL-172154+azacitidine, 1.0 mg/kg SL-172154+azacitidine and azacitidine monotherapy. Patients will be stratified based on the TP53 mutation status (TP53m vs TP53wt) and bone marrow blast count at study entry (\<5% vs ≥5%).

Study Timeline

• Study First Submitted: 2022-02-15
• Study First Submitted QC: 2022-03-03
• Study First Posted: 2022-03-11
• Study Start: 2022-03-17
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-01
• Last Update Posted: 2024-10-03
• Primary Completion: 2024-11
• Study Completion: 2024-11

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 160

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
SL-172154	SL-172154	Patients will receive intravenous administration
SL-172154 + Azacitidine	SL-172154	Patients will receive intravenous administration of SL-172154 and Azacitidine.
SL-172154 + Azacitidine + Venetoclax	SL-172154	Patients will receive intravenous administration of SL-172154 and Azacitidine plus oral venetoclax.
Part D-Previously untreated HR-MDS 1:1:1 Randomization	SL-172154	Previously untreated MDS patients with or without TP53 mutation will be randomized to receive the following: * 3 mg/kg SL-172154 + Azacitidine * 1 mg/kg SL-172154 + Azacitidine * Azacitidine Monotherapy

Primary Outcome Measures

Name	Time	Method
Part D- To evaluate safety and anti-tumor activity of SL-172154 at 1.0 mg/kg vs 3.0 mg/kg administered with azacitidine in higher-risk MDS subjects	From Day 1 to 90 days after Last Dose of SL-172154	Complete remission (CR) based on Investigator assessed disease response according to International Working Group (IWG) 2006 criteria
To evaluate the safety and tolerability of SL-172154 administered alone or with Azacitidine OR Azacitidine + Venetoclax in subjects with higher-risk MDS or AML	From Day 1 to 90 days after Last Dose of SL-172154	Incidence of all treatment emergent adverse events
To select the recommended Phase 2 dose (RP2D) for SL-172154 administered with Azacitidine OR Azacitidine + Venetoclax in subjects with higher-risk MDS or AML	From Day 1 to 90 days after Last Dose of SL-172154	Defined based on the rate of dose limiting toxicities (DLTs)
Part D- To evaluate safety and anti-tumor activity of SL-172154 at 1.0 mg/kg and 3.0 mg/kg administered with azacitidine vs azacitidine monotherapy in higher-risk MDS subjects	From Day 1 to 90 days after Last Dose of SL-172154	Incidence of all treatment emergent adverse events

Secondary Outcome Measures

Name	Time	Method
Assess preliminary evidence of anti-tumor activity of SL-172154 administered alone or with Azacitidine OR Azacitidine + Venetoclax in subjects with higher-risk MDS or AML	Approximately 24 months	Investigator assessed disease response according to International Working Group (IWG) 2006 criteria (MDS) or European LeukemiaNet (ELN) 2017 criteria (AML)
To evaluate immunogenicity to SL-172154 during and after treatment of SL-172154 administered alone or with Azacitidine OR Azacitidine + Venetoclax in subjects with higher-risk MDS or AML	Approximately 24 months	Number/proportion of subjects with positive or negative anti-drug antibody (ADA) titer
Time at which maximum concentration of SL-172154 is observed (Tmax)	Approximately 24 months	The Tmax is the time at which the maximum concentration of SL-172154 is observed following single and multiple doses
Maximum serum concentration (Cmax) of SL-172154	Approximately 24 months	To assess the pharmacokinetic profile of SL-172154 when administered alone or with azacitidine OR azacitidine + venetoclax in subjects with higher-risk MDS or AML
Clearance (CL)	Approximately 24 months	Clearance of Sl-172154
Area under the serum concentration-time curve (AUC)	Approximately 24 months	The AUC is the area under the serum concentration time curve following single and multiple doses of SL-172154
Terminal elimination half-life (t1/2)	Approximately 24 months	Terminal elimination half-life (t1/2) of SL-172154
Volume of distribution	Approximately 24 months	Volume of distribution of SL-172154
Part D: To assess preliminary evidence of anti-tumor efficacy of SL-172154 administered with azacitidine compared to azacitidine monotherapy in subjects with higher-risk MDS	Approximately 24 months	Overall survival

Trial Locations

Locations (23)

University of Cincinnati Medical Center; 🇺🇸 Cincinnati, Ohio, United States

UPMC Hillman Cancer Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Baylor Scott & White Research Institute; 🇺🇸 Dallas, Texas, United States

UCLA Medical Center-Bowyer Oncology Center; 🇺🇸 Los Angeles, California, United States

City of Hope; 🇺🇸 Duarte, California, United States

Yale Cancer Center; 🇺🇸 New Haven, Connecticut, United States

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

The University of Chicago; 🇺🇸 Chicago, Illinois, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Norton Cancer Institute; 🇺🇸 Louisville, Kentucky, United States

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

START Midwest; 🇺🇸 Grand Rapids, Michigan, United States

Roswell Park Comprehensive Cancer Center; 🇺🇸 Buffalo, New York, United States

University of North Carolina, Lineberger Comprehensive Cancer Center; 🇺🇸 Chapel Hill, North Carolina, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

VCU Massey Cancer Center; 🇺🇸 Richmond, Virginia, United States

Tom Baker Cancer Centre; 🇨🇦 Calgary, Alberta, Canada

Princess Margaret Cancer Centre; 🇨🇦 Toronto, Ontario, Canada

Jewish General Hospital; 🇨🇦 Montréal, Quebec, Canada

King's College Hospital NHS Foundation Trust; 🇬🇧 London, Denmark Hill, United Kingdom

University Hospitals Plymouth NHS Trust, Derriford Hospital; 🇬🇧 Crownhill, Plymouth, United Kingdom

Imperial College Healthcare NHS Trust; 🇬🇧 London, United Kingdom

The Christie NHS Foundation Trust; 🇬🇧 Manchester, United Kingdom