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

TERMINATEDPHASE1

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

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)

NCT03940352•Novartis Pharmaceuticals

View on ClinicalTrials.gov

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. 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.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

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.

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).
+1 more criteria

Locations (9)

Duke University Medical Center .

Durham, North Carolina, United States

Novartis Investigative Site

Melbourne, Victoria, Australia

Novartis Investigative Site

Helsinki, Finland

Novartis Investigative Site

Heidelberg, Germany

Novartis Investigative Site

Würzburg, Germany

Novartis Investigative Site

Milan, MI, Italy

Novartis Investigative Site

Roma, RM, Italy

Novartis Investigative Site

Singapore, Singapore

Novartis Investigative Site

Madrid, Spain

Key Dates

Start Date

June 24, 2019

Primary Completion Date

August 20, 2024

Completion Date

August 20, 2024

Last Updated

October 10, 2025

Enrollment

ACTUAL participants

Conditions

Acute Myeloid Leukemia (AML)High-risk Myelodysplastic Syndrome (MDS)

Interventions

HDM201

DRUG

MBG453

BIOLOGICAL

Venetoclax

DRUG

BCL2i CLAG-M in R/R Acute Myeloid Leukemia

NCT06660368

Relapsed or Refractory Acute Myeloid Leukemia (AML)

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RECRUITINGPHASE1

CLN-049 in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)

NCT05143996

Relapsed/Refractory Acute Myeloid Leukemia (AML)Myelodysplastic Syndrome (MDS)

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: October 10, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

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

Inclusion Criteria

Exclusion Criteria

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