Evidence map›Paper›PMID 41310838›Full record

Trial reportJournal of hematology & oncology2025

A phase 1/2 study of DS-1594 menin inhibitor in relapsed/refractory acute leukemias.

Jayastu Senapati, Marina Konopleva, Ghayas C Issa, Elias Jabbour, Tapan Kadia, Courtney DiNardo, Gautam Borthakur, Naveen Pemmaraju, Nicholas J Short, Musa Yilmaz and 17 more

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

Trial report in Journal of hematology & oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Review
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

27 authors.

Jayastu SenapatiDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, 77030, Houston, TX, USA.
Marina KonoplevaDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, 77030, Houston, TX, USA.
Ghayas C IssaDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, 77030, Houston, TX, USA.
Elias JabbourDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, 77030, Houston, TX, USA.
Tapan KadiaDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, 77030, Houston, TX, USA.
Courtney DiNardoDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, 77030, Houston, TX, USA.
Gautam BorthakurDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, 77030, Houston, TX, USA.
Naveen PemmarajuDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, 77030, Houston, TX, USA.
Nicholas J ShortDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, 77030, Houston, TX, USA.
Musa YilmazDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, 77030, Houston, TX, USA.
Indraneel DeshmukhDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, 77030, Houston, TX, USA.
Joie AlvarezDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, 77030, Houston, TX, USA.
Sanam LoghaviDepartment of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, USA.
Guilin TangDepartment of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, USA.
Hussein A AbbasDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, 77030, Houston, TX, USA.
Michael AndreeffDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, 77030, Houston, TX, USA.
Kapil BhallaDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, 77030, Houston, TX, USA.
Narasimha M MiddeDaiichi Sankyo, Inc, Basking Ridge, NJ, USA.
Nabil SaidDaiichi Sankyo, Inc, Basking Ridge, NJ, USA.
Amy NoyalisDaiichi Sankyo, Inc, Basking Ridge, NJ, USA.
Derek E MiresDaiichi Sankyo, Inc, Basking Ridge, NJ, USA.
Jing NingDepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, USA.
Lianchun XiaoDepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, USA.
Farhad RavandiDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, 77030, Houston, TX, USA.
Guillermo Garcia-ManeroDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, 77030, Houston, TX, USA.
Hagop M KantarjianDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, 77030, Houston, TX, USA.
Naval G DaverDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, 77030, Houston, TX, USA. ndaver@mdanderson.org.

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
NCI NIH HHS P30 CA016672University of Texas MD Anderson Cancer Center Grant CA016672University of Texas MD Anderson SPORE C1100632
6 · The paper itself

Abstract

Several menin inhibitors are in development targeting menin dependent leukemias, however available preclinical results show variable level of activity. We report the phase 1 portion (to establish a recommended phase 2 dose [RP2D]) and pharmacokinetic analysis of a phase 1/2 first-in-human clinical trial of DS-1594b menin inhibitor. Eligible patients included adults (≥ 18 years of age) with relapsed/refractory (R/R) acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) including but not restricted to those with KMT2A-rearrangement (r) or NPM1 mutation. Seventeen patients at a median of age 56 years (range, 19-82 years) were treated, 15 (88%) had R/R AML, and 2 (12%) had R/R B-ALL; 9 (53%) had a KMT2A-r but none had an NPM1 mutation. The median prior lines of therapy was 3 (range 1-8) and 5 patients (29%) had received prior menin inhibitors. Five dose escalation cohorts were evaluated; no RP2D was established, and the trial was stopped at phase 1 due to a decision by supporting company due to lack of efficacy at studied dose levels and portfolio realignment. Differentiation syndrome (DS) was seen in 5 patients (29%); 2 in cohort 1 (70 mg twice daily, n = 4) 1 each had grade 1 and grade 4 DS, 3 patients in cohort 2 (50 mg twice daily/100 mg daily, n = 4) of whom 2 had grade 2 and 1 patient had grade 3 DS (considered as dose limiting toxicity). No DS was noted at cohort 3 (20 mg/day), and in subsequent dose-escalation cohorts (cohorts 4 and 5) a lead-in ramp-up dosing starting at 20 mg/day was instituted to improve tolerability. Other relevant treatment emergent adverse events of grade ≥ 3 included infections; pneumonia and febrile neutropenia in 7 patients each (41%), and sepsis in 6 patients (35%). No study drug related deaths were noted. No patient achieved a response, however 4 patients (23%) had > 25% bone marrow blast reduction. Pharmacokinetic analysis showed DS-1594b reached maximum concentration approximately in 2 h with total exposure increasing with escalating doses and reached stead-state by Cycle 1 Day 8. DS-1594b showed limited efficacy at the doses tested but appeared safe with a lead-in dosing approach.

Indexed as

Antineoplastic AgentsLeukemia, Myeloid, AcutePrecursor Cell Lymphoblastic Leukemia-LymphomaProto-Oncogene ProteinsAdultAgedAged, 80 and overFemaleHumansMaleMiddle AgedNucleophosminRecurrenceYoung AdultAntineoplastic AgentsMEN1 protein, humanNPM1 protein, humanNucleophosminProto-Oncogene ProteinsAcute myeloid leukemiaDifferentiation syndromeKMT2AMenin inhibitorNPM1

Identifiers

PMID41310838
PMCPMC12661886

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Registered trials

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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 OpenQuestion graph.