Clinical trial NCT04878432: STIMULUS MDS-US : Sabatolimab Added to HMA in Higher Risk MDS
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myelodysplastic Syndrome (MDS)
Keywords: sabatolimab
phase II
MBG453
TIM-3
decitabine
azacitidine
oral decitabine
INQOVI
myelodysplastic syndrome (MDS)
adult
MDS
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2021-05-07
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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))

Detailed 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).

Eligibility criteria: 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

Primary outcomes:
measure: Number of treatment emergent adverse events and serious adverse events
timeFrame: Baseline up to approximately 12 months plus 30 - 150 day safety follow up dependent on HMA
Secondary outcomes:
measure: Complete remission (CR) rate according to International Working Group (IWG) for MDS (2006) * as per investigator assessment by 12 months.
timeFrame: Baseline, by 12 months
measure: Progression free survival in participants with intermediate, high or very high risk MDS
timeFrame: Baseline, every 12 weeks up to approximately 12 months
measure: Overall Survival
timeFrame: Baseline, every 12 weeks up to approximately 24 months
measure: Leukemia-free survival
timeFrame: Baseline, every 12 weeks up to approximately 12 months
measure: Percentage of participants with complete response, marrow complete response and/or partial response
timeFrame: Baseline, every 12 weeks up to approximately 24 months
measure: Duration of complete remission
timeFrame: Baseline, every 12 weeks up to approximately 12 months
measure: Time to complete remission
timeFrame: Baseline, every 12 weeks up to approximately 12 months
measure: Percentage of participants with improvement in RBC/platelets transfusion independence
timeFrame: Baseline, every 12 weeks up to approximately 12 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates .
state: Arizona
city: Denver
country: United States
facility: SCRI-Colorado Blood Cancer Institute
state: Colorado
city: New Haven
country: United States
facility: Yale University School Of Medicine .
state: Connecticut
city: Orlando
country: United States
facility: Advent Health Orlando
state: Florida
city: Worcester
country: United States
facility: Uni of Massachusetts Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University Of Michigan .
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Institute Div.of Hematology/Oncology
state: Michigan
city: New York
country: United States
facility: Tisch Hospital NYU Langone
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Durham
country: United States
facility: Duke Cancer Institute
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Of Cleveland
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Houston
country: United States
facility: Uni Of TX MD Anderson Cancer Cntr
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology San Antonio USO
state: Texas
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: