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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05275439
Recruitment Status : Recruiting
First Posted : March 11, 2022
Last Update Posted : January 25, 2023
Sponsor:
Information provided by (Responsible Party):
Shattuck Labs, Inc.

Tracking Information
First Submitted Date  ICMJE February 15, 2022
First Posted Date  ICMJE March 11, 2022
Last Update Posted Date January 25, 2023
Actual Study Start Date  ICMJE March 17, 2022
Estimated Primary Completion Date February 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 3, 2022)
  • 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 [ Time Frame: 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 [ Time Frame: From Day 1 to 90 days after Last Dose of SL-172154 ]
    Defined based on the rate of dose limiting toxicities (DLTs)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 3, 2022)
  • 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 [ Time Frame: 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 [ Time Frame: Approximately 24 months ]
    Number/proportion of subjects with positive or negative anti-drug antibody (ADA) titer
  • Maximum serum concentration (Cmax) of SL-172154 [ Time Frame: 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
  • Time at which maximum concentration of SL-172154 is observed (Tmax) [ Time Frame: Approximately 24 months ]
    The Tmax is the time at which the maximum concentration of SL-172154 is observed following single and multiple doses
  • Area under the serum concentration-time curve (AUC) [ Time Frame: 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) [ Time Frame: Approximately 24 months ]
    Terminal elimination half-life (t1/2) of SL-172154
  • Clearance (CL) [ Time Frame: Approximately 24 months ]
    Clearance of Sl-172154
  • Volume of distribution [ Time Frame: Approximately 24 months ]
    Volume of distribution of SL-172154
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 1 Study of Shattuck Labs (SL)-172154 in Subjects With MDS or AML
Official Title  ICMJE An Open-Label Phase 1a/1b Dose Escalation and Expansion Cohort Study of SL-172154 (SIRPα-Fc-CD40L) in Combination With Azacitidine or With Azacitidine and Venetoclax for the Treatment of Subjects With Higher-Risk Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML)
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).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Intervention  ICMJE Drug: SL-172154
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.
Other Names:
  • Azacitidine
  • Venetoclax
Study Arms  ICMJE
  • Experimental: SL-172154
    Patients will receive intravenous administration
    Intervention: Drug: SL-172154
  • Experimental: SL-172154 + Azacitidine
    Patients will receive intravenous administration of SL-172154 and Azacitidine.
    Intervention: Drug: SL-172154
  • Experimental: SL-172154 + Azacitidine + Venetoclax
    Patients will receive intravenous administration of SL-172154 and Azacitidine plus oral venetoclax.
    Intervention: Drug: SL-172154
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 3, 2022)
107
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2024
Estimated Primary Completion Date February 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Subject has voluntarily agreed to participate by giving written informed consent in accordance with International Council for Harmonisation/Good Clinical Practice (ICH/GCP) guidelines and applicable local regulations.
  2. Age ≥ 18 years.
  3. For subjects with AML, confirmation of AML diagnosis by 2016 World Health Organization (WHO) criteria [Arber, 2016] classification, excluding acute promyelocytic leukemia (APL).
  4. Subjects with MDS must have:

    1. 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.
    2. confirmation of intermediate, high or very high risk category by Revised International Prognostic Scoring System (IPSS-R)
  5. 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.
  6. Subjects with relapsed/refractory disease (as defined in Inclusion criterion 5) following at least 1 prior line of therapy but no more than 4 prior lines of therapy for AML or MDS.
  7. Subjects diagnosed with MDS must be previously untreated. Prior MDS therapy with lenalidomide or supportive care in the form of transfusions or growth factors is allowed.
  8. All subjects must have documentation of at least one tumor protein 53 (TP53) gene mutation/deletion based on local test.
  9. Subjects with previously untreated de novo AML or secondary AML with TP53 gene mutation or deletion and who are unlikely to benefit from standard intensive induction therapy or refuse intensive induction therapy at time of enrollment are eligible. All subjects must have documentation of at least one TP53 gene mutation/deletion based on local test. Subjects with secondary AML after MDS must not have received prior chemotherapy or no more than 2 cycles of prior hypomethylating agent for MDS.
  10. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0, 1, or 2
  11. Laboratory values must meet the criteria outlined in the protocol.
  12. Willing to provide consent for bone marrow aspirate samples for exploratory research at baseline and on-treatment per schedule described in the Schedule of Assessments.
  13. For subjects with relapsed/refractory disease, recovery from prior anti-cancer treatments including surgery, radiotherapy, chemotherapy or any other anti-cancer therapy to baseline or ≤ Grade 1.
  14. Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test within 72 hours of the first dose of study treatment.
  15. Male subjects with female partners of childbearing potential must have azoospermia from a prior vasectomy or underlying medical condition or agree to use an acceptable method of contraception during treatment and for 30 days (which exceeds 5 half-lives) or for the duration required by local regulatory guidance, whichever is longer, after last dose of study treatment.

Exclusion Criteria:

  1. Subject with relapsed or refractory disease has received treatment for AML or MDS with any of the following:

    1. Chimeric antigen receptor (CAR)-T cell therapy
    2. Prior treatment with anti-cluster of differentiation 47 (CD47) targeting agent or cluster of differentiation 40 (CD40) agonist within 28 days prior to
    3. the first dose of study treatment.
    4. Prior treatment with signal-regulatory protein alpha (SIRPα)-targeting antibody
    5. 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
  2. Evidence of active central nervous system (CNS) involvement with leukemia
  3. Subjects requiring agents other than hydroxyurea to control blast counts within 14 days prior to the first dose of study treatment.
  4. Evidence of active bleeding or bleeding diathesis or major coagulopathy (including familial)
  5. [Only for Cohorts including Venetoclax in the regimen] Subject has received strong and/or moderate cytochrome P450, family 3, subfamily A (CYP3A) inducers within 7 days prior to the first dose of study treatment.
  6. Use of corticosteroids or other immunosuppressive medication, current or within 14 days of the first dose of study treatment
  7. Receipt of live attenuated vaccine within 30 days of first dose of SL-172154 treatment, the exception is that vaccines for coronavirus disease 19 (COVID-19) are permitted.
  8. Subject has active, uncontrolled infection (e.g, viral, bacterial, or fungal). Subjects are eligible if infection is controlled with antibiotics, antivirals and/or antifungals.
  9. [Only for Cohorts including Venetoclax in the regimen] Subject has a malabsorption syndrome or other condition that precludes enteral route of administration.
  10. Symptomatic peptic ulcer disease or gastritis, active diverticulitis, other serious gastrointestinal disease associated with diarrhea within 6 months of first dose of study treatment.
  11. Clinically significant or uncontrolled cardiac disease including any of the following:

    • Myocarditis
    • Unstable angina within 6 months from D1 of study treatment
    • Acute myocardial infarction within 6 months from D1 of study treatment
    • Uncontrolled hypertension
    • New York Heart Association (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)
  12. Subject has chronic respiratory disease that requires continuous oxygen, or significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, or any other medical condition that in the opinion of the investigator would adversely affect his/her participation in the study.
  13. Subjects who have had any major surgical procedure within 14 days of first dose of study treatment.
  14. Subject is a woman who is pregnant or breast feeding or planning to become pregnant or breast feed while enrolled in this study.
  15. Psychiatric illness/social circumstances that would limit compliance with study requirements and substantially increase the risk of adverse events (AEs) or compromised ability to provide written informed consent.
  16. Presence of another malignancy that requires active therapy and that in the opinion of the investigator and Sponsor would interfere with the monitoring of disease assessments in this study.
  17. Known hypersensitivity to any of the study medications including excipients of Azacitidine.
  18. Has undergone solid organ transplantation.
  19. Known or active human immunodeficiency virus (HIV) infection
  20. Known or active infection with hepatitis B (positive for hepatitis B surface antigen [HBsAg]) or hepatitis C virus ([HCV]; if hepatitis C virus (HCV) antibody (Ab) test is positive check for HCV ribonucleic acid [RNA]).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Shattuck Clinical Trials 919-864-2700 clinicaltrials@shattucklabs.com
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05275439
Other Study ID Numbers  ICMJE Shattuck Labs (SL) 03-OHD-104
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Shattuck Labs, Inc.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Shattuck Labs, Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Shattuck Labs Shattuck Labs
PRS Account Shattuck Labs, Inc.
Verification Date January 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP