A Study of Siremadlin in Combination With Venetoclax Plus Azacitidine in Adult Participants With Acute Myeloid Leukemia (AML) Who Are Ineligible for Chemotherapy.

A Phase Ib/II Open Label Dose Confirmation, Proof of Concept Study of Siremadlin in Combination With Venetoclax Plus Azacitidine in Unfit Adult AML Participants Who Responded Sub-optimally to First-line Venetoclax Plus Azacitidine Treatment and in Participants With Newly Diagnosed Unfit AML Presenting With High-risk Clinical Features

ClinicalTrials.gov Identifier: NCT05155709

Novartis Reference Number: CHDM201I12201

Last Update: May 24, 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

A study of siremadlin in combination with venetoclax plus azacitidine in adult participants with AML who are ineligible for chemotherapy.

Acute Myeloid Leukemia
Phase 1
Phase 2
Overall status 
Start date 
May 17, 2022
Completion date 
Jan 02, 2026
18 Years - 99 Years (Adult, Older Adult)


Siremadlin is a capsule taken orally once a day (QD) and comes in 10 mg and 20 mg strengths
Venetoclax is a tablet taken orally once a day (QD) and comes in 10 mg, 50 mg and 100 mg strengths.
Azacitidine is a powder for suspension for injection or powder for solution for infusion taken intravenously or subcutaneously according to standard local clinical practice

Eligibility Criteria

Inclusion Criteria:

- Age at the date of signing the informed consent form (ICF): Arm 1 and Arm 2: ≥ 18 years

- Participants diagnosed with AML based on WHO 2016 classification (Arber et al 2016) who are ineligible for standard induction chemotherapy and: Arm 1 : have received at least 2 cycles and not more than 4 cycles of first-line venetoclax plus azacitidine treatment and have not achieved a CR, CRi, CRh or MLFS.

Arm 2 : newly diagnosed AML with adverse genetic risk stratification (according to ELN 2017) (except TP53 mutation positive participants).

Participant must be considered ineligible for standard of care intensive induction chemotherapy defined by the following:

75 years of age; OR
18 to 74 years of age with at least one of the following co-morbidities: Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or 3; Cardiac history of congestive heart failure (CHF) requiring treatment or Ejection Fraction ≤ 50% or chronic stable angina; DLCO ≤ 65% or FEV1 ≤ 65%.

Participants must have an ECOG performance status:

0 to 2 for participants ≥ 75 years of age. OR 0 to 3 for participants ≥ 18 to 74 years of age.

WBC < 25x109/L
AST and ALT ≤ 3 × ULN
Estimated Glomerular Filtration Rate (eGFR)≥ 60 mL/min/1.73 m2

Exclusion Criteria:

Prior exposure to MDM2-inhibitor therapy at any time.
Participants with TP53 mutation positive, as defined by local TP53 testing.
Participants with del17p.
Participants with AML-M3 / APL (Acute promyelocytic leukemia) with PML-RARA (Promyelocytic leukemia/retinoic acid receptor alpha) or with AML secondary to Down's syndrome.
Participants treated with FLT3 inhibitors
Participants who require treatment with moderate or strong CYP3A4 inducers within 14 days prior to starting study treatment, or are expected to receive moderate or strong CYP3A4 inducers during the entire study
Participants who require treatment with substrates of CYP3A4/5 with a narrow therapeutic index.

Other protocol-defined inclusion/exclusion criteria may apply at the end

Study Locations

Novartis Investigative Site
Budapest, 1085
Novartis Investigative Site
Alor Setar, 05460
Novartis Investigative Site
Selangor, 68000


Novartis Pharmaceuticals
Novartis Pharmaceuticals

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