A Study of MBG453 in Combination With Azacitidine and Venetoclax in AML Patients Unfit for Chemotherapy (STIMULUS-AML1)

Novartis

Status and phase: Active, not recruiting; Phase 2

Conditions: Acute Myeloid Leukemia

Treatments: Drug: MBG453; Drug: Venetoclax; Drug: Azacitidine

Study type: Interventional

Funder types: Industry

Identifiers

NCT04150029

CMBG453C12201

2019-000439-14 (EudraCT Number)

Details and patient eligibility

About

This trial will seek to extend the preliminary findings of efficacy of MBG453 in combination with hypomethylating agents (HMA) by evaluating MBG453 in combination with the HMA azacitidine and the Bcl-2 inhibitor venetoclax.

Full description

The primary purpose of Part 1 (Safety Run-in) is to rule out excessive toxicity of MBG453, when administered in combination with azacitidine and venetoclax.

The primary purpose of the combined Part 1 and Part 2 (Safety run-in and Expansion Part) is to evaluate efficacy of MBG453, when administered in combination with azacitidine and venetoclax in adult patients with newly diagnosed AML, who are not suitable for treatment with intensive chemotherapy.

There will be an analyis of the CR rate, after all subjects have completed at least 12 cycles of treatment ( cycle =28Days) or discontinued earlier.

Enrollment: 90 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Signed informed consent must be obtained prior to participation in the study.
2. Age ≥ 18 years at the date of signing the informed consent form (ICF)
3. Newly diagnosed with AML based on 2016 WHO classification (Arber et al 2016) and not suitable for intensive chemotherapy defined as: age ≥75, ECOG performance Status 2 or 3, or any of the following comomorbitities: severe cardiac comorbities (including congestive heart failure, LVEF ≤ 50%, chronic stable Angina) , pulmonary comorbidity (DLCO ≤ 65% or FEVI ≤ 65%). moderate hepatic impairment (with total Bilirubin >1.5 to 3x ULN) , renal impairment (eGFR≥ 30 ml/min/1.73m^2 to 45 30 ml/min/1.73m^2), or other comorbidity incompatible with intensive chemotherapy per Investigator assessement and approved by the Novartis Medical monitor)
4. .Not planned for hematopoietic stem-cell transplantation (HSCT)
5. .Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 , 2 or 3

Exclusion criteria

1. Prior exposure to TIM-3 directed therapy
2. History of severe hypersensitivity reactions to any ingredient of study drug(s) (azacitidine, venetoclax or MGB453) or monoclonal antibodies (mAbs) and/or their excipients
3. Current use or use within 14 days prior to randomization 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.
4. Previous treatment at any time, with any of the following antineoplastic agents, approved or investigational; checkpoint inhibitors, venetoclax and hypomethylating agents (HMAs) such as decitabine or azacitidine.
5. Active autoimmune disease requiring systemic therapy (e.g.corticosteroids).
6. Live vaccine administered within 30 Days prior to randomization

Other protocol-defined Inclusion/Exclusion may apply.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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90 participants in 1 patient group

MBG453+Venetoclax +Azacitidine

Experimental group

Description:

Patients will receive MBG453 in combination with Venetoclax and Azacitidine

Treatment:

Drug: Azacitidine

Drug: Venetoclax

Drug: MBG453