Evidence map›Paper›PMID 40439882›Full record

ArticleCancer chemotherapy and pharmacology2025

Phase 1 studies of the indenoisoquinolines LMP776 and LMP744 in patients with solid tumors and lymphomas.

Geraldine O'Sullivan Coyne, Shivaani Kummar, Larry V Rubinstein, Deborah Wilsker, Nancy Moore, Murielle Hogu, Richard Piekarz, Joe Covey, Jan H Beumer, Katherine V Ferry-Galow and 11 more

2 registry-linked trialsAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer chemotherapy and pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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.

NCT01051635 phase1completednot on this map

A Phase I Study of Indenoisoquinolines LMP400 and LMP776 in Adults With Relapsed Solid Tumors and Lymphomas

TypeinterventionalSponsorNational Cancer Institute (NCI)Ran2010 to 2017Enrolled55ConditionsNeoplasms, LymphomaArmsLMP400, LMP776
NCT03030417 phase1completednot on this map

A Phase I Study of Indenoisoquinoline LMP744 in Adults With Relapsed Solid Tumors and Lymphomas

TypeinterventionalSponsorNational Cancer Institute (NCI)Ran2017 to 2023Enrolled36ConditionsSolid Tumors, LymphomaArmsLMP744, Ondansetron, Olanzapine, Lorazepam, Diphenoxylate hydrocholoride (HCL) + Atropine Sulfate
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. 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

21 authors.

Geraldine O'Sullivan CoyneDivision of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, 31 Center Drive, Building 31, Room 3A44, Bethesda, MD, 20892, USA.
Shivaani KummarDivision of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, 31 Center Drive, Building 31, Room 3A44, Bethesda, MD, 20892, USA.
Larry V RubinsteinBiometric Research Program, NCI, NIH, Bethesda, MD, USA.
Deborah WilskerClinical Pharmacodynamics Biomarker Program, Applied/Developmental Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Nancy MooreDivision of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, 31 Center Drive, Building 31, Room 3A44, Bethesda, MD, 20892, USA.
Murielle HoguDivision of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, 31 Center Drive, Building 31, Room 3A44, Bethesda, MD, 20892, USA.
Richard PiekarzCancer Therapeutics Evaluation Program, NCI, NIH, Bethesda, MD, USA.
Joe CoveyDivision of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, 31 Center Drive, Building 31, Room 3A44, Bethesda, MD, 20892, USA.
Jan H BeumerUPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Katherine V Ferry-GalowClinical Pharmacodynamics Biomarker Program, Applied/Developmental Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Liza C VillaruzUPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Melinda G HollingsheadBiological Testing Branch, NCI, NIH, Frederick, MD, USA.
Julianne L HolleranUPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Joshua J DeppasUPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Yves PommierDevelopmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, NCI, NIH, Bethesda, MD, USA.
Brian KoDivision of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, 31 Center Drive, Building 31, Room 3A44, Bethesda, MD, 20892, USA.
Barry C JohnsonDivision of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, 31 Center Drive, Building 31, Room 3A44, Bethesda, MD, 20892, USA.
Ralph E ParchhmentClinical Pharmacodynamics Biomarker Program, Applied/Developmental Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Percy IvyCancer Therapeutics Evaluation Program, NCI, NIH, Bethesda, MD, USA.
James H DoroshowDivision of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, 31 Center Drive, Building 31, Room 3A44, Bethesda, MD, 20892, USA.
Alice P ChenDivision of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, 31 Center Drive, Building 31, Room 3A44, Bethesda, MD, 20892, USA. chenali@mail.nih.gov.

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHRISTOPHER J. BAKKENIST · 1988 to 2026
$158.0M
Cancer Pharmacokinetics Research SpecialistR50CA211241 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI PARISE, ROBERT · 2016 to 2025
$1.8M
CCR NIH HHS HHSN261200800001CNCI NIH HHS HHSN261200800001ENCI NIH HHS P30 CA047904NCI NIH HHS R50 CA211241
6 · The paper itself

Abstract

purposeIndenoisoquinolines are a class of topoisomerase I (TOP1) inhibitors designed to overcome clinical limitations of camptothecins. Three indenoisoquinolines (LMP400, LMP776, and LMP744) demonstrated activity in murine models and a comparative canine lymphoma study. Clinical data for LMP400 were previously reported (NCT01051635). The maximum tolerated dose (MTD), safety, and clinical data from phase 1 studies of LMP776 (NCT01051635) and LMP744 (NCT03030417) are reported herein.

methodsPatients ≥ 18 years of age with advanced, refractory solid tumors or lymphomas received either LMP776 (n = 34) or LMP744 (n = 35) intravenously following a Simon accelerated titration design. Both LMP776 and LMP744 were administered daily for 5 days (QDx5) in 28-day cycles. Adverse events and clinical responses were evaluated according to CTCAE and RECIST v1.1 criteria, respectively. Pharmacokinetic and pharmacodynamic changes were evaluated.

resultsThe MTD of LMP776 was 12 mg/m

conclusionMTDs and safety profiles are reported for LMP776 and LMP744. Target engagement by an indenoisoquinoline was measured for the first time in human samples.

Indexed as

IsoquinolinesLymphomaNeoplasmsTopoisomerase I InhibitorsAdultAgedAged, 80 and overFemaleHumansMaleMaximum Tolerated DoseMiddle AgedIsoquinolinesTopoisomerase I InhibitorsClinical trialIndenoisoquinolinePharmacodynamicTopoisomerase

Identifiers

PMID40439882
PMCPMC12122562

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Registered trials

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.