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

NCT05275439 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: SL03-OHD-104
• Study Type: interventional
• Target: 106
• Locations: 3 countries
• Sites: 23

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.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (3)

• Safety Profile of SL-172154 Monotherapy or in Combination With Azacitidine

  Number of participants with treatment emergent adverse events from dose escalation and dose expansion cohorts

  From Day 1 to study completion, an average of 2-5 months depending on the treatment arm

• Recommended Phase 2 Dose of SL-172154 Administered With Azacitidine

  Based on review of all data, including safety, tolerability, PK, antitumor activity, and PD effects

  From Day 1 to study completion, an average of 2-5 months depending on the treatment arm

• Safety Profile of SL-172154 in Combination With Azacitidine or Azacitidine Monotherapy

  Number of participants with treatment emergent adverse events from Part D cohorts

  From Day 1 to study completion, an average of 2-5 months depending on the treatment arm

Secondary Outcomes (8)

• Preliminary Evidence of Anti-tumor Activity of SL-172154 Administered Alone or With Azacitidine

  Approximately 24 months

• Immunogenicity to SL-172154 During and After Treatment of SL-172154 Alone or With Azacitidine

  Approximately 24 months

• Maximum Serum Concentration (Cmax) of SL-172154

  Cycle 1 Day 1/2, Cycle 1 Day 15/16, and Cycle 2 Day 1/2 (cycle = 28 days)

• Time at Which Maximum Concentration of SL-172154 is Observed (Tmax)

  Cycle 1 Day 1/2, Cycle 1 Day 15/16, and Cycle 2 Day 1/2 (cycle = 28 days)

• Area Under the Serum Concentration-time Curve (AUC)

  Cycle 1 Day 1, Cycle 1 Day 15/16, and Cycle 2 Day 1 (cycle = 28 days)

Study Arms (4)

SL-172154

EXPERIMENTAL

Patients will receive intravenous administration

Drug: SL-172154

SL-172154 + Azacitidine

EXPERIMENTAL

Patients will receive intravenous administration of SL-172154 and Azacitidine.

Drug: SL-172154; Drug: Azacitidine (AZA)

SL-172154 + Azacitidine + Venetoclax

EXPERIMENTAL

Patients will receive intravenous administration of SL-172154 and Azacitidine plus oral venetoclax.

Drug: SL-172154; Drug: Azacitidine (AZA); Drug: Venetoclax

Part D-Previously untreated HR-MDS 1:1:1 Randomization

EXPERIMENTAL

Patients will randomized to receive intravenous administration of the following: * 3 mg/kg SL-172154 + Azacitidine * 1 mg/kg SL-172154 + Azacitidine * Azacitidine Monotherapy

Drug: SL-172154; Drug: Azacitidine (AZA)

Interventions

SL-172154 DRUG

The investigational product (IP), SL-172154, is a novel fusion protein consisting of human SIRPα and CD40L (SIRPα -Fc-CD40L) linked via a human Fc.

Part D-Previously untreated HR-MDS 1:1:1 Randomization; SL-172154; SL-172154 + Azacitidine; SL-172154 + Azacitidine + Venetoclax

Azacitidine (AZA) DRUG

Chemotherapy drug approved for use in MDS and AML.

Part D-Previously untreated HR-MDS 1:1:1 Randomization; SL-172154 + Azacitidine; SL-172154 + Azacitidine + Venetoclax

Venetoclax DRUG

Drug approved for use in AML.

SL-172154 + Azacitidine + Venetoclax

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.
• 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.

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.

Sponsors & Collaborators

• Shattuck Labs, Inc.: lead

Study Sites (23)

City of Hope

Duarte, California, 91010, United States

Location

UCLA Medical Center-Bowyer Oncology Center

Los Angeles, California, 90095, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06510, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

The University of Chicago

Chicago, Illinois, 60637, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40202, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

START Midwest

Grand Rapids, Michigan, 49546, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263, United States

Location

University of North Carolina, Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Baylor Scott & White Research Institute

Dallas, Texas, 75246, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

VCU Massey Cancer Center

Richmond, Virginia, 23219, United States

Location

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2C1, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

King's College Hospital NHS Foundation Trust

London, Denmark Hill, SE5 9RS, United Kingdom

Location

University Hospitals Plymouth NHS Trust, Derriford Hospital

Crownhill, Plymouth, PL6 8DH, United Kingdom

Location

Imperial College Healthcare NHS Trust

London, W12 0HS, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Azacitidine; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: VP, Clinical Operations
• Organization: Shattuck Labs

clinicaltrials@shattucklabs.com

919-864-2700

Study Officials

• Shattuck Labs

  Shattuck Labs

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2022
• First Posted: March 11, 2022
• Study Start: March 17, 2022
• Primary Completion: February 6, 2025
• Study Completion: February 6, 2025
• Last Updated: March 18, 2026
• Results First Posted: March 18, 2026

Record last verified: 2026-02

Locations

GB (4); US (16); CA (3)