STIMULUS MDS-US : Sabatolimab Added to HMA in Higher Risk MDS

Myelodysplastic Syndrome (MDS) Clinical Trial

Official title:

Single-arm, Open Label, Phase II Study of MBG453 (Sabatolimab) Added to FDA Approved Hypomethylating Agents of Investigator's Choice (IV/SC/Oral) for Patients With Intermediate, High or Very High Risk Myelodysplastic Syndrome (MDS) as Per IPSS-R Criteria (US Multi-center) (STIMULUS MDS-US)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04878432
• Other study ID #: CMBG453B1US01
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 17, 2022
• Est. completion date: June 14, 2024

Study information

• Verified date: May 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Main objective of this study is to describe and evaluate safety and efficacy of MBG453 (sabatolimab) in combination with FDA approved HMAs of investigator's choice (IV Decitabine or Azacitidine /SC Azacitidine /Oral Decitabine (cedazuridine combination (INQOVI))

Description:

This is a single-arm, non- randomized, open label, phase II multi-center study of intravenous MBG453 (sabatolimab) added to FDA approved Hypomethylating agents of investigator's choice (IV/SC/ Oral) in adult participants with intermediate, high or very high risk myelodysplastic syndrome (MDS) as per IPSS-R criteria. There are three separate periods of this study: 1. Screening period (signing of written informed consent through Day 1); 2. Core phase for 12 months; 3. Extension phase for efficacy and/or survival status (up to 12 months after core phase) 4. Post treatment safety follow-up monitoring for adverse events (AEs) for 30 days following the last dose of azacitidine or decitabine or INQOVI (oral decitabine), or 150 days following the last dose of MBG453 (sabatolimab), whichever is later).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 39
• Est. completion date: June 14, 2024
• Est. primary completion date: September 8, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

• Signed informed consent must be obtained prior to participation in the study.
• Age = 18 years at the date of signing the informed consent form (ICF).
• Morphologically confirmed diagnosis of a myelodysplastic syndrome (MDS) primary or secondary based on 2016 WHO classification (Arber et al 2016) by investigator assessment with one of the following Prognostic Risk Categories, based on the International Prognostic Scoring System (IPSS-R). Note: MDS diagnosis history will be

recorded in the CRF:

• Very high (> 6 points)
• High (> 4.5 - = 6 points)
• Intermediate (> 3 - = 4.5 points)
• Not suitable at the time of screening for immediate myeloablative/ chemotherapy or hematopoietic stem cell transplantation based on investigator assessment of age, comorbidities, local guidelines, institutional practice (any or all of these).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
• AST and ALT = 3 × upper limit of normal (ULN).
• Total bilirubin = 2 × ULN (except in the setting of isolated Gilbert syndrome).
• Estimated Glomerular Filtration Rate (eGFR) = 30 mL/min/1.73m2 (estimation based on Modification of Diet in Renal Disease (MDRD) formula, by local laboratory).
• Patient is able to communicate with the investigator and has the ability to comply with the requirements of the study procedures.

Exclusion Criteria:

• Prior exposure to TIM-3 directed therapy at any time. Prior therapy with immune checkpoint inhibitors (e.g. anti-CTLA4, anti-PD-1, anti-PD-L1, or anti-PD-L2), cancer vaccines are allowed only if the last dose of the drug was administered more than 4 months prior to enrollment.
• Previous treatment for intermediate, high or very high risk myelodysplastic syndromes (based on IPSS-R) with chemotherapy or other antineoplastic agents including lenalidomide and hypomethylating agent (HMAs) such as decitabine or azacitidine or INQOVI (oral decitabine) (patients who had up to 1 cycle of HMAs can be included). However, previous treatment with hydroxyurea is permitted.
• Diagnosis of acute myeloid leukemia (AML) including acute promyelocytic leukemia and extra-medullary acute myeloid leukemia based on WHO 2016 classification (Arber et al 2016).
• Diagnosis of Chronic myelomonocytic leukemia (CMML), or primary or secondary myelofibrosis based on 2016 WHO classification (Arber et al 2016).
• History of organ transplant or allogenic hematopoietic stem cell transplant
• Participants with prior malignancy, except:

1. Participants with history of lower risk MDS treated by supportive care (e.g. growth factors, TGF-beta agents) or untreated are eligible

2. Participants with history of lower risk MDS who were treated adequately with lenalidomide and then failed are eligible

3. Participants with history of adequately treated malignancy for which no anticancer systemic therapy (namely chemotherapy, radiotherapy or surgery) is ongoing or required during the course of the study. Participants who are receiving adjuvant therapy such as hormone therapy are eligible.

• Participants with Myelodysplastic syndrome (MDS) based on 2016 WHO classification (Arber et al 2016) with revised International Prognostic Scoring System (IPSS-R) = 3

Related Conditions & MeSH terms

• Myelodysplastic Syndrome (MDS)
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• MBG453
Solution for intravenous infusion
• Azacitidine
Solution for subcutaneous injection or intravenous infusion
• Decitabine
Solution for intravenous infusion
• INQOVI (oral decitabine)
Tablet for oral administration

Locations

Country	Name	City	State
United States	University of Michigan .	Ann Arbor	Michigan
United States	Cleveland Clinic	Cleveland	Ohio
United States	University Hospitals Of Cleveland	Cleveland	Ohio
United States	SCRI- Colorado Blood Cancer Institute	Denver	Colorado
United States	Karmanos Cancer Institute Div.of Hematology/Oncology	Detroit	Michigan
United States	Duke Cancer Institute	Durham	North Carolina
United States	Uni of TX MD Anderson Cancer Cntr	Houston	Texas
United States	Yale University School Of Medicine .	New Haven	Connecticut
United States	Mount Sinai Medical Center	New York	New York
United States	Tisch Hospital NYU Langone	New York	New York
United States	Advent Health Orlando	Orlando	Florida
United States	Mayo Clinic Arizona	Phoenix	Arizona
United States	Texas Oncology San Antonio USO	San Antonio	Texas
United States	Arizona Oncology Associates .	Tucson	Arizona
United States	Uni of Massachusetts Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of treatment emergent adverse events and serious adverse events	Adverse events will be assessed at each visit. Any clinically significant laboratory value or vital sign determined by the investigator to meet the definition of an adverse event will be reported.	Baseline up to approximately 12 months plus 30 - 150 day safety follow up dependent on HMA
Secondary	Complete remission (CR) rate according to International Working Group (IWG) for MDS (2006) * as per investigator assessment by 12 months.	Complete remission with MBG453 (sabatolimab) in combination with HMAs (IV/SC/Oral) in participants with intermediate, high, or very high risk MDS by 12 months	Baseline, by 12 months
Secondary	Progression free survival in participants with intermediate, high or very high risk MDS	Defined as time from enrollment to disease progression (including transformation to leukemia per WHO 2016 classification), relapse from CR according to IWG-MDS or death due to any cause, whichever occurs first, as per investigator assessment by 12 months post LPFT	Baseline, every 12 weeks up to approximately 12 months
Secondary	Overall Survival	Time from enrollment to death due to any cause	Baseline, every 12 weeks up to approximately 24 months
Secondary	Leukemia-free survival	Time from enrollment to > 20% blasts in bone marrow/peripheral blood (per WHO 2016 classification) or death due to any cause	Baseline, every 12 weeks up to approximately 12 months
Secondary	Percentage of participants with complete response, marrow complete response and/or partial response	Percentage of complete response, marrow complete response, and/or partial response according to IWG-MDS response criteria as per investigator assessment	Baseline, every 12 weeks up to approximately 24 months
Secondary	Duration of complete remission	Time from the date of the first documented CR to the date of first documented relapse from CR or death due to any cause, whichever occurs first	Baseline, every 12 weeks up to approximately 12 months
Secondary	Time to complete remission	Time from first treatment to the first documented complete remission	Baseline, every 12 weeks up to approximately 12 months
Secondary	Percentage of participants with improvement in RBC/platelets transfusion independence	Transfusion independence is defined as less than 3 units of transfusion within any 8 consecutive weeks on study	Baseline, every 12 weeks up to approximately 12 months