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

Stopped early · Phase 1

Conditions studied: Acute Myeloid Leukemia, Myelodysplastic Syndromes

In brief

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.

Key facts

Study ID

NCT05275439

Run by

Shattuck Labs, Inc.

People needed

106

Starts

2022-03-17

Expected to finish

2025-02-06

Last updated by the study team

2026-03-18

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Participants are eligible to be included in the study only if all the following criteria apply.
• Subject has voluntarily agreed to participate by giving written informed consent in accordance with ICH/GCP guidelines and applicable local regulations.
• Age ≥ 18 years.
• For subjects with AML, confirmation of AML diagnosis by 2016 WHO criteria [Arber, 2016] (World Health Organization [WHO] classification, excluding acute promyelocytic leukemia [APL]).
• Subjects with MDS must have:
• morphologically confirmed diagnosis of MDS by 2016 WHO criteria [Arber, 2016] with <20% blasts in bone marrow per bone marrow biopsy/aspirate or peripheral blood.
• confirmation of intermediate, high or very high risk category by Revised International Prognostic Scoring System (IPSS-R).
• Subjects with a diagnosis of any of the following are excluded: Atypical CML, juvenile myelomonocytic leukemia (JMML), chronic myelomonocytic leukemia (CMML), and unclassifiable MDS/ myeloproliferative neoplasm (MPN).
• [Dose Escalation Cohort - SL-172154 Monotherapy] Subjects with AML must have relapsed/refractory disease (≥5% blasts by manual aspirate differential, flow cytometry, or immunohistochemistry) following at least 1 prior line of therapy but no more than 4 prior lines of therapy. Subjects with higher-risk MDS must have relapsed/refractory disease following at least 1 prior line but no more than 4 prior lines of therapy.
• Prior hydroxyurea or other supportive care in the form of transfusions or growth factors will not be considered prior therapy.
• Subjects who have undergone allogeneic-hematopoietic cell transplantation (HCT) are eligible if they are at least 6 months post-HCT, have relapsed AML or MDS as defined above, are not on treatment or prophylaxis for graft versus host disease (GVHD) for at least 6 weeks before administration of study treatment, and have no active GVHD.
• Subjects must not be eligible for rescue chemotherapy and allogeneic-HCT per local or institutional guidelines at the time of screening.
• [Dose Escalation Cohort - SL-172154 Administered with Azacitidine] Subjects with relapsed/refractory AML and MDS (as defined in Inclusion criterion 5) following at least 1 prior line of therapy but no more than 4 prior lines of therapy.
• Treatment for MDS preceding secondary AML will not be considered as a prior line of therapy for secondary AML.
• Prior hydroxyurea or other supportive care in the form of transfusions or growth factors will not be considered prior therapy.
• Subjects who have undergone allogeneic-HCT are eligible if they are at least 6 months post-HCT, have relapsed AML or MDS as defined above, are not on treatment or prophylaxis for GVHD for at least 6 weeks before the first dose of study treatment, and have no active GVHD.
• Subjects must not be eligible for rescue chemotherapy and allogeneic-HCT per local or institutional guidelines at the time of screening.
• In addition, previously untreated subjects meeting either of the following criteria are eligible for this cohort:
• Previously untreated subjects with AML with known adverse cytogenetics who fall into the adverse ELN risk group and who are unlikely to benefit from standard intensive induction therapy or refuse intensive induction therapy at time of enrollment.
• Previously untreated subjects with MDS with documentation of at least one TP53 gene mutation or deletion based on a local test. Prior MDS therapy with lenalidomide or other supportive care in the form of transfusions or growth factors is allowed.
• [Dose Expansion Cohort Part A: SL-172154 Administered with Azacitidine] Subjects diagnosed with MDS must be previously untreated. Prior MDS therapy with lenalidomide, luspatercept or supportive care in the form of transfusions or growth factors is allowed. Up to 1 cycle of prior therapy with a hypomethylating agent is permitted. Subjects with newly diagnosed treatment-related MDS are also eligible for enrollment.
• [Dose Escalation - Safety Run-in Cohort AND Dose Expansion Cohort Part B: SL 172154 Administered with Azacitidine and Venetoclax] Subjects with AML must be previously untreated as defined by:
• Subject must be ineligible for induction therapy with a standard cytarabine and anthracycline induction regimen due to age or co-morbidities as defined by the following:
• ≥ 75 years of age
• ≥ 60 to 74 years of age with at least one of the following co-morbidities:

You may not qualify if…

• Participants are excluded from the study if any of the following criteria apply:
• [Monotherapy and Combination Regimen Dose Escalation Cohorts] Prior treatment with:
• CAR-T cell therapy within 3 months from the first dose of the study drug.
• Prior treatment with anti-CD47 targeting agent or CD40 agonist within 28 days prior to the first dose of study treatment.
• Prior treatment with signal-regulatory protein alpha (SIRPα)-targeting agent.
• Other experimental therapies for AML or MDS within 14 days or at least 5 half-lives (whichever is shorter) prior to the first dose of study treatment.
• Evidence of active CNS involvement with leukemia.
• Subjects requiring agents other than hydroxyurea to control blast counts within 14 days prior to the first dose of study treatment.
• Evidence of active bleeding or bleeding diathesis or major coagulopathy (including familial).
• [Only for Cohorts Including Venetoclax in the Regimen] Subject has received strong and/or moderate CYP3A inducers within 7 days prior to the first dose of venetoclax.
• Use of systemic corticosteroids (>10 mg daily of prednisone or equivalent) or other non-steroidal immunosuppressive medication, current or within 14 days of the first dose of study treatment with the following exceptions (i.e., the following are allowed within 14 days of first dose):
• Topical, intranasal, inhaled, ocular, intraarticular corticosteroids
• Physiological doses of replacement steroid (e.g., for adrenal insufficiency)
• Steroid premedication for hypersensitivity reactions (e.g., reaction to IV contrast) or a brief course of treatment of non-autoimmune conditions (e.g., transfusion reactions, delayed-type hypersensitivity reaction caused by contact allergen).
• Receipt of live attenuated vaccine within 30 days of first dose of SL-172154 treatment.
• Subject has active, uncontrolled infection (e.g., viral, bacterial, or fungal). Subjects are eligible if infection is controlled with antibiotics, antivirals and/or antifungals.
• [Only for Cohorts Including Venetoclax in the Regimen] Subject has a malabsorption syndrome or other condition that precludes the enteral route of administration.
• Symptomatic peptic ulcer disease or gastritis, active diverticulitis, other serious gastrointestinal disease associated with diarrhea within 6 months of first dose of study treatment.
• Clinically significant or uncontrolled cardiac disease including any of the following:
• Myocarditis
• Unstable angina within 6 months from first dose of study treatment
• Acute myocardial infarction within 6 months from first dose of study treatment
• Uncontrolled hypertension
• NYHA Class III or IV congestive heart failure
• Clinically significant (symptomatic) cardiac arrhythmias (e.g., sustained ventricular tachycardia, second- or third- degree atrioventricular (AV) block without a pacemaker, circulatory collapse requiring vasopressor or inotropic support, or arrhythmia not stabilized on therapy)

Where it is running

• City of Hope — Duarte, California, United States
• UCLA Medical Center-Bowyer Oncology Center — Los Angeles, 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
• Norton Cancer Institute — Louisville, Kentucky, United States
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States
• University of Michigan — Ann Arbor, Michigan, 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
• 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
• 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 — Montreal, 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

Full record on ClinicalTrials.gov

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