Evidence map›Paper›PMID 39030997›Full record

ArticleCancer medicine2024

Phase 1 dose escalation study of the MDM2 inhibitor milademetan as monotherapy and in combination with azacitidine in patients with myeloid malignancies.

Courtney D DiNardo, Rebecca Olin, Eunice S Wang, Barry Skikne, Joseph Rosenthal, Prasanna Kumar, Hiroyuki Sumi, Yoshiyuki Hizukuri, Ying Hong, Parul Patel and 4 more

Abstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Courtney D DiNardoDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.ORCID 0000-0001-9003-0390
Rebecca OlinUniversity of California, San Francisco, California, USA.
Eunice S WangRoswell Park Comprehensive Care Center, Buffalo, New York, USA.
Barry SkikneUniversity of Kansas Medical Center, Kansas City, Kansas, USA.
Joseph RosenthalDepartment of Pediatrics, City of Hope, Duarte, California, USA.
Prasanna KumarDaiichi Sankyo Inc., Basking Ridge, New Jersey, USA.
Hiroyuki SumiDaiichi Sankyo Co., Tokyo, Japan.
Yoshiyuki HizukuriDaiichi Sankyo Co., Tokyo, Japan.
Ying HongDaiichi Sankyo Inc., Basking Ridge, New Jersey, USA.
Parul PatelDaiichi Sankyo Inc., Basking Ridge, New Jersey, USA.
Takahiko SekiDaiichi Sankyo Inc., Basking Ridge, New Jersey, USA.
Tao DuanDaiichi Sankyo Inc., Basking Ridge, New Jersey, USA.
Arnaud LesegretainDaiichi Sankyo Inc., Basking Ridge, New Jersey, USA.
Michael AndreeffDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMouse double minute-2 homolog (MDM2) plays a key role in downregulating p53 activity in hematologic malignancies, and its overexpression is associated with poor outcomes.

methodsThis phase 1 study assessed the safety and efficacy of different dosing regimens of the MDM2 inhibitor milademetan as monotherapy and in combination with azacitidine (AZA) in patients with relapsed or refractory acute myeloid leukemia or high-risk myelodysplastic syndromes.

resultsSeventy-four patients (monotherapy, n = 57; milademetan-AZA combination, n = 17) were treated. The maximum tolerated dose of milademetan was 160 mg once daily given for the first 14-21 days of 28-day cycles as monotherapy and on Days 5-14 in combination with AZA. Dose-limiting toxicities were gastrointestinal, fatigue, or renal/electrolyte abnormalities. Treatment-emergent adverse events related to milademetan occurred in 82.5% and 64.7% of participants in the monotherapy and AZA combination arms, respectively. Two participants (4.2%) in the monotherapy arm achieved complete remission (CR), and 1 (2.1%) achieved CR with incomplete blood count recovery (CRi). Two participants (13.3%) achieved CRi in the combination arm. New TP53 mutations, detected only during milademetan monotherapy, were found pre-existing below standard detection frequency by droplet digital polymerase chain reaction.

interpretationMilademetan was relatively well tolerated in this population; however, despite signals of activity, clinical efficacy was minimal.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsAzacitidineLeukemia, Myeloid, AcuteMaximum Tolerated DoseMyelodysplastic SyndromesProto-Oncogene Proteins c-mdm2AdultAgedAged, 80 and overCarbolinesFemaleHeterocyclic Compounds, 4 or More RingsHumansMaleMiddle AgedTreatment OutcomeAzacitidineCarbolinesHeterocyclic Compounds, 4 or More RingsMDM2 protein, humanPM 01183Proto-Oncogene Proteins c-mdm2acute myeloid leukemiamilademetanmouse double minute‐2 homologmyelodysplastic syndromes

Identifiers

PMID39030997
PMCPMC11258486

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.