A Study of Sabatolimab in Combination With Azacitidine and Venetoclax in High or Very High Risk MDS Participants

A Single-arm, Open-label, Phase II Study of Sabatolimab in Combination With Azacitidine and Venetoclax in Adult Participants With High or Very High Risk Myelodysplastic Syndromes (MDS) as Per IPSS-R Criteria

ClinicalTrials.gov Identifier: NCT04812548

Novartis Reference Number: CMBG453B12203

Last Update: May 11, 2022

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

The purpose of the study is to find out if the new drug sabatolimab when given in combination with azacitidine and venetoclax, is safe and has beneficial effects in participants with high or very high risk myelodysplastic syndrome (MDS) who are not suitable for treatment with intensive chemotherapy or a stem-cell transplant (HSCT).

Condition 
Myelodysplastic Syndrome (MDS)
Phase 
Phase 2
Overall status 
Recruiting
Start date 
May 31, 2021
Completion date 
Dec 06, 2025
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Drug
sabatolimab
Sabatolimab will be administered at a low dose (Safety run-in (Part 1) cohort 1) or a high dose (Safety run-in (Part 1) cohort 2 and Expansion (Part 2)) via i.v. infusion over 30 minutes on Day 8 of every treatment cycle.
Drug
azacitidine
A standard dose of azacitidine will be given subcutaneously or intravenously every day for seven consecutive days on days 1-7 of a confirmed treatment cycle. In keeping with standard clinical practice, the alternative schedules for five consecutive days on days 1-5, followed by a two day break, then two consecutive days on days 8-9 will be permitted (alternative schedule).
Drug
venetoclax
Venetoclax film-coated tablets will be administered at a dose of 400 mg orally or corresponding reduced dose for concomitant use with P-gp inhibitors or moderate or strong CYP3A4 inhibitors, once a day, from C1D1 to C1D14 during the treatment cycle. No ramp-up for venetoclax is necessary.

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 myelodysplastic syndrome (MDS) based on 2016 WHO classification (Arber et al, 2016) by local investigator assessment with one of the following Prognostic Risk Categories, based on the revised International Prognostic Scoring System (IPSS-R) (Greenberg et al 2012):

Very high (> 6 points)
High (> 4.5-6 points)
Not immediately eligible for hematopoietic stem-cell transplantation (HSCT) or intensive chemotherapy at the time of screening due to individual clinical factors such as age, comorbidities and performance status, donor availability (de Witte et al 2017)
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

Exclusion Criteria:

Prior exposure to TIM-3 directed therapy or any BCL-2 inhibitor (including venetoclax) at any time
Prior therapy with immune check point inhibitors (e.g. anti-CTLA4, anti-PD-1, anti-PD-L1, or anti-PD-L2) or cancer vaccines is not allowed if the last dose of the drug was administered within 4 months prior to start of treatment
Previous first-line treatment for very high risk or high risk myelodysplastic syndromes (based on IPSS-R,Greenberg et al 2012 and Arber et al, 2016) with any antineoplastic agents, approved or investigational, including for example chemotherapy, lenalidomide and hypomethylating agents (HMAs) such as decitabine or azacitidine However, a one single cycle of HMAs treatment only started prior to enrollment is allowed.
Live vaccine administered within 30 days prior to start of treatment
Current use or use within 14 days prior to start of treatment of systemic steroid therapy (> 10 mg/day prednisone or equivalent) or any immunosuppressive therapy. Topical, inhaled, nasal, ophthalmic steroids are allowed. Replacement therapy, steroids given in the context of a transfusion, are allowed and not considered a form of systemic treatment
History of severe hypersensitivity reactions to any ingredient of study drug(s) (azacitidine, venetoclax or sabatolimab) or monoclonal antibodies (mAbs) and/or their excipients
Participants with Myelodysplastic syndrome (MDS) based on 2016 WHO classification (Arber et al, 2016) with revised International Prognostic Scoring System (IPSS-R) ≤ 4.5

Other protocol-defined Inclusion/Exclusion may apply.

Study Locations

United States
City of Hope National Medical Center Medical Oncology & Therapeutic
Recruiting
Duarte, 91010 - California
Contact: (626-471-9200) Vinod Pullarkat
United States
University of Texas MD Anderson Cancer Center
Recruiting
Houston, 77030 - Texas
Contact: (713-792-2921) Guillermo Garcia-Manero
United States
Australia
Novartis Investigative Site
Recruiting
Melbourne, 3004
Victoria
Australia
Belgium
Novartis Investigative Site
Recruiting
Brasschaat, 2930
-
Belgium
France
Novartis Investigative Site
Recruiting
Marseille, 13273
-
France
Novartis Investigative Site
Recruiting
Nice Cedex, 06202
-
France
Germany
Novartis Investigative Site
Recruiting
Duesseldorf, 40479
-
Germany
Novartis Investigative Site
Recruiting
Leipzig, 04103
-
Germany
Novartis Investigative Site
Recruiting
Stuttgart, 70376
-
Germany
Greece
Novartis Investigative Site
Recruiting
Alexandroupolis, 681 00
Evros
Greece
Novartis Investigative Site
Recruiting
Patras, 265 00
-
Greece
Hungary
Novartis Investigative Site
Recruiting
Nyiregyhaza, 4400
-
Hungary
Italy
Novartis Investigative Site
Recruiting
Firenze, 50134
FI
Italy
Novartis Investigative Site
Recruiting
Genova, 16132
GE
Italy
Spain
Novartis Investigative Site
Recruiting
Barcelona, 08036
Catalunya
Spain

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
Name: 
Novartis Pharmaceuticals
Phone: 

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