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Acute Myeloid Leukemia (AML)Phase 1NCT03940352

HDM201 in Combination With MBG453 or Venetoclax in Patients With Acute Myeloid Leukemia (AML) or High-risk Myelodysplastic Syndrome (MDS)

A Phase 1 study testing HDM201, MBG453 and Venetoclax in people with Acute Myeloid Leukemia (AML) and High-risk Myelodysplastic Syndrome (MDS), run by Novartis Pharmaceuticals at 9 sites in 7 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This was a phase 1b, multi-arm, open-label study of HDM201 in combination with MBG453 or venetoclax in subjects with AML or high-risk MDS. For all subjects, TP53wt status had to be characterized by, at a minimum, no mutations noted in exons 5, 6, 7 and 8. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
HDM201, MBG453 and Venetoclax
Could I receive a placebo?
No, everyone receives an active treatment
How many people
52 participants
Where
9 sitesin 7 countries
Study dates
24 Jun 2019to 20 Aug 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Main Inclusion Criteria:

  • Male or female patients ≥ 18 years of age at the date of ICF signature who present with one of the following:
  1. Relapsed/refractory AML following ≥1 prior therapies (but ≤3 prior therapies) who have relapsed or exhibited refractory disease (primary failure) and are deemed by the Investigator not to be candidates for standard therapy, including re-induction with cytarabine or other established chemotherapy regimens for patients with AML (patients who are suitable for standard re-induction chemotherapy or hematopoietic stem cell transplantation and willing to receive it are excluded)
  2. First line AML patient unfit for standard induction chemotherapy (includes both de novo and secondary AML), except in countries where approved therapies are available. Patients who are suitable for hematopoietic stem cell transplantation and willing to receive it are excluded.
  3. High-risk MDS patient (high and very high-risk groups according to rIPSS) who have failed hypomethylating agent therapy.
  • ECOG performance status ≤ 1
  • TP53wt tumor. At minimum exons 5, 6, 7 and 8 in the TP53 gene must be sequenced and determined to contain no mutations. The TP53 status must be obtained from a bone-marrow sample, collected no longer than 3 months before signing the main ICF.
  • Patient must be a candidate for serial bone marrow aspirate and/or biopsy according to the institutional guidelines and be willing to undergo a bone marrow aspirate and/or biopsy at screening, during and at the end of therapy on this study. Exceptions may be considered after documented discussion with Novartis.

Main Exclusion Criteria:

Patients eligible for this study must not meet any of the following criteria:

  • Prior combination treatment with compounds having the same mode of action:
  • mdm2 or mdm4 inhibitors combined with TIM-3 inhibitors (for patients enrolled in treatment arm1)
  • mdm2 or mdm4 inhibitors combined with Bcl-2 inhibitor (for patients enrolled in treatment arm2)
  • History of severe hypersensitivity reactions to any ingredient of study drug(s) and other monoclonal antibodies (mAbs) and/or their excipients.
  • Patients with acute promyelocytic leukemia with PML-RARA.
  • Allogeneic stem cell transplant (HSCT) within last 6 months and/or active GvHD requiring systemic immunosuppressive therapy.
  • GI disorders impacting absorption of oral HDM201 or venetoclax.
  • Evidence of active bleeding or bleeding diathesis or major coagulopathy (including familial).
  • Patients with active, known or suspected autoimmune disease (treatment arm 1 only).

Other eligibility criteria apply.

Trial locations and contacts

9 sites in 7 countries.

9 sites in 7 countries

Germany2 sites

  • Novartis Investigative Site

    Heidelberg, 69120

  • Novartis Investigative Site

    Würzburg, 97080

Other trials in Germany

Italy2 sites

  • Novartis Investigative Site

    Milan, MI, 20132

  • Novartis Investigative Site

    Roma, RM, 00161

Other trials in Italy

United States1 site

  • Duke University Medical Center .

    Durham, North Carolina, 27710

Other trials in United States

Australia1 site

  • Novartis Investigative Site

    Melbourne, Victoria, 3004

Other trials in Australia

Finland1 site

  • Novartis Investigative Site

    Helsinki, FIN 00290

Other trials in Finland

Singapore1 site

  • Novartis Investigative Site

    Singapore, 119228

Other trials in Singapore

Spain1 site

  • Novartis Investigative Site

    Madrid, 28041

Other trials in Spain

About this study

Official title: A Phase Ib, Multi-arm, Open-label, Study of HDM201 in Combination With MBG453 or Venetoclax in Adult Subjects With Acute Myeloid Leukemia (AML) or High-risk Myelodysplastic Syndrome (MDS)

This was a phase 1b, multi-arm, open-label study of HDM201 in combination with MBG453 or venetoclax in subjects with AML or high-risk MDS.

For all subjects, TP53wt status had to be characterized by, at a minimum, no mutations noted in exons 5, 6, 7 and 8.

Read more

Two treatment arms enrolled subjects in parallel to characterize the safety, tolerability, PK, PD and preliminary antitumor activity of HDM201+MBG453 (treatment arm 1) and HDM201+venetoclax (treatment arm 2).

  • In the treatment arm 1, subjects received HDM201 in combination with MBG453.
  • In the treatment arm 2, subjects received HDM201 in combination with venetoclax. Venetoclax dose was gradually increased (ramp-up) over a period of 4 to 5 days to achieve the daily target dose tested that was subsequently continued.

Upon the completion of the escalation part, MTD(s) and/or RD(s) of HDM201 in combination with MBG453 or venetoclax in AML and high-risk MDS subjects was planned to be determined for each treatment arm.

Being tested
HDM201, MBG453, Venetoclax
Keywords
Phase Ib, BHLRM, AML, MDS, HDM201, TP53, MBG453, TIM-3, venetoclax, Bcl-2
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HDM201Drug

    Capsule

  • MBG453Biological

    LIVI (Liquid in vial) Concentrate for Solution for infusion

  • VenetoclaxDrug

    Tablet

Study groups in NCT03940352
Study groupRoleWhat they receive
treatment arm1: HDM201+MBG453ExperimentalPhase Ib (escalation)
Receives: Drug: HDM201; Biological: MBG453
treatment arm2: HDM201+venetoclaxExperimentalPhase Ib (escalation)
Receives: Drug: HDM201; Drug: Venetoclax

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) as a measure of safety

    Month 24 is assumed to be study end

    Measured: at month 24

  2. Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) as a measure of safety

    Month 24 is assumed to be study end

    Measured: at month 24

  3. Incidence of dose limiting toxicities (DLTs) of treatment

    end of first cycle

    Measured: at day 28

  4. Frequency of dose interuptions

    Month 24 is assumed to be study end

    Measured: at month 24

  5. Frequency of dose reductions

    Month 24 is assumed to be study end

    Measured: at month 24

  6. Dose intensities

    measured in mg/ day Month 24 is assumed to be study end

    Measured: at month 24

Secondary outcomes (20)

  1. Overall Response Rate (ORR)

    Month 24 is assumed to be study end

    Measured: at month 24

  2. Best Overall Response (BOR)

    Month 24 is assumed to be study end

    Measured: at month 24

  3. Event Free Survival (EFS) for AML (Cheson 2003) or Progression Free Survival (PFS) for MDS (Cheson 2006)

    Month 24 is assumed to be study end

    Measured: at month 24

  4. Relapse Free Survival (RFS) for AML (Cheson 2003) or Time To Response (TTR) for MDS (Cheson 2006)

    Month 24 is assumed to be study end

    Measured: at month 24

  5. Duration Of Response (DOR) for AML (Cheson 2003) and MDS (Cheson 2006)

    Month 24 is assumed to be study end

    Measured: at month 24

  6. Presence of anti-MBG453 antibodies (treatment arm 1 HD201+MBG453)

    Measured: at Day 1, Day 29 and at month 24

  7. Concentration of HDM201 (Treatment arm 1 HDM201+MBG453 and treatment arm 2 HDM201+venetoclax)

    Measured: at Day 1, Day 2, Day 5, Day 6 and Day 29

  8. Concentration of MBG453 (treatment arm 1 HDM201+MBG453)

    Measured: at Day 1, Day 2, Day 8, Day 11, Day 15, Day 29 and at month 24

  9. Concentration of venetoclax (treatment arm 2 HDM201+venetoclax)

    Measured: at Day 1, Day 2, Day 3, Day 5, Day 6, Day 8, Day 9, Day 14, Day 15 and Day 29

  10. PK parameter (AUC) of HDM201 (Treatment arm 1 HDM201+MBG453 and treatment arm 2 HDM201+venetoclax)

    Cycle 6

    Measured: at month 6

  11. PK parameter (Cmax) of HDM201 (Treatment arm 1 HDM201+MBG453 and treatment arm 2 HDM201+venetoclax)

    Cycle 6

    Measured: at month 6

  12. PK parameter (Tmax) of HDM201 (Treatment arm 1 HDM201+MBG453 and treatment arm 2 HDM201+venetoclax)

    Cycle 6

    Measured: at month 6

  13. PK parameter (AUC) of MBG453 (treatment arm 1 HDM201+MBG453)

    Cycle 6

    Measured: at month 6

  14. PK parameter (Cmax) of MBG453 (treatment arm 1 HDM201+MBG453)

    Cycle 6

    Measured: at month 6

  15. PK parameter (Tmax) of MBG453 (treatment arm 1 HDM201+MBG453)

    Cycle 6

    Measured: at month 6

  16. PK parameter (AUC) of venetoclax (treatment arm 2 HDM201+venetoclax)

    Cycle 6

    Measured: at month 6

  17. PK parameter (Cmax) of venetoclax (treatment arm 2 HDM201+venetoclax)

    Cycle 6

    Measured: at month 6

  18. PK parameter (Tmax) of venetoclax (treatment arm 2 HDM201+venetoclax)

    Cycle 6

    Measured: at month 6

  19. Changes from baseline in GDF-15 (Treatment arm 1 HDM201+MBG453 and treatment arm 2 HDM201+venetoclax)

    Measured: at Day 1 and Day 2

  20. Changes from baseline in soluble TIM-3 (Treatment arm 1 HDM201+MBG453)

    Cycle 6

    Measured: at month 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 May 2019
  2. Study start24 Jun 2019
  3. Primary completion20 Aug 2024
  4. Study completion20 Aug 2024

Why it stopped: Business decision

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
52 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03940352
Sponsor's protocol ID
CHDM201H12101C
Other IDs
2018-004001-62, 2018
Status last verified
Oct 2025
First submitted
2 May 2019
Last updated
10 Oct 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing HDM201, MBG453 and Venetoclax in people with Acute Myeloid Leukemia (AML) and High-risk Myelodysplastic Syndrome (MDS), run by Novartis Pharmaceuticals at 9 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 10 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Germany, Italy, United States, Australia, Finland and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Business decision). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) as a measure of safety (time frame: at month 24). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03940352.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2025.

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