Evidence map›Paper›PMID 38683495›Full record

ArticleTargeted oncology2024

ASCT2-Targeting Antibody-Drug Conjugate MEDI7247 in Adult Patients with Relapsed/Refractory Hematological Malignancies: A First-in-Human, Phase 1 Study.

Michael Maris, Gilles Salles, Won Seog Kim, Tae Min Kim, Roger M Lyons, Martha Arellano, Reem Karmali, Gary Schiller, Elizabeth Cull, Camille N Abboud and 10 more

Registry-linked trialAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Targeted oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03106428 (A Phase 1 Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Antitumor Activity of MEDI7247 in Patients With Selected Relapsed/Refractory Hematological Malignancies), which is not on this map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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.

NCT03106428 phase1completednot on this map

A Phase 1 Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Antitumor Activity of MEDI7247 in Patients With Selected Relapsed/Refractory Hematological Malignancies

TypeinterventionalSponsorMedImmune LLCRan2017 to 2020Enrolled67ConditionsAcute Myeloid Leukemia, Multiple Myeloma, Diffuse Large B-cell LymphomaArmsMEDI7247
3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

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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

20 authors.

Michael MarisColorado Blood Cancer Institute and Sarah Cannon Research Institute, Denver, CO, USA.
Gilles SallesCentre Hospitalier Lyon Sud, Pierre Benite, France.
Won Seog KimSamsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Tae Min KimSeoul National University Hospital, Seoul, South Korea.
Roger M LyonsTexas Oncology, US Oncology, San Antonio, TX, USA.
Martha ArellanoWinship Cancer Institute, Emory University, Atlanta, GA, USA.
Reem KarmaliNorthwestern University Feinberg School of Medicine, Chicago, IL, USA.
Gary SchillerDavid Geffen School of Medicine, UCLA Medical Center, Los Angeles, CA, USA.
Elizabeth CullPrisma Health, Cancer Institute-Eastside, Greenville, SC, USA.
Camille N AbboudSiteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA.
Connie BatleviMemorial Sloan Kettering Cancer Center, New York, NY, USA.
Ioannis KagiampakisTranslational Medicine Bioinformatics, AstraZeneca, Gaithersburg, MD, USA.
Marlon C RebelattoEarly Oncology Research and Development, AstraZeneca, Gaithersburg, MD, USA.
Young LeeEarly Oncology Research and Development, AstraZeneca, Gaithersburg, MD, USA.
Lyndon C KirbyEarly Oncology Research and Development, AstraZeneca, Gaithersburg, MD, USA.
Fujun WangBiostatistics, AstraZeneca, Gaithersburg, MD, USA.
John BothosEarly Oncology Research and Development, AstraZeneca, Gaithersburg, MD, USA.
Danielle M TownsleyEarly Oncology Research and Development, AstraZeneca, Gaithersburg, MD, USA.
Amir T Fathi *Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Vincent Ribrag *Department of Hematology, Drug Development Department (DITEP), Institut Gustave Roussy, 114 rue Edouard Vaillant, 94805, Villejuif Cedex, France. vincent.ribrag@igr.fr.ORCID 0000-0002-5221-353X

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

backgroundMEDI7247 is a first-in-class antibody-drug conjugate (ADC) consisting of an anti-sodium-dependent alanine-serine-cysteine transporter 2 antibody-conjugated to a pyrrolobenzodiazepine dimer.

objectiveThis first-in-human phase 1 trial evaluated MEDI7247 in patients with hematological malignancies. PATIENTS AND

methodsAdults with acute myeloid leukemia (AML), multiple myeloma (MM), or diffuse large B-cell lymphoma (DLBCL) relapsed or refractory (R/R) to standard therapies, or for whom no standard therapy exists, were eligible. Primary endpoints were safety and determination of the maximum tolerated dose (MTD). Secondary endpoints included assessments of antitumor activity, pharmacokinetics (PK), and immunogenicity.

resultsAs of 26 March 2020, 67 patients were treated (AML: n = 27; MM: n = 18; DLBCL: n = 22). The most common MEDI7247-related adverse events (AEs) were thrombocytopenia (41.8%), neutropenia (35.8%), and anemia (28.4%). The most common treatment-related grade 3/4 AEs were thrombocytopenia (38.8%), neutropenia (34.3%), and anemia (22.4%). Anticancer activity (number of responders/total patients evaluated) was observed in 11/67 (16.4%) patients. No correlation was observed between ASCT2 expression and clinical response. Between-patient variability of systemic exposure of MEDI7247 ADC and total antibody were high (AUC

conclusionsThrombocytopenia and neutropenia limited repeat dosing. Although limited clinical activity was detected, the dose-escalation phase was stopped early without establishing an MTD. The study was registered with ClinicalTrials.gov (NCT03106428).

Indexed as

Hematologic NeoplasmsImmunoconjugatesAdultAgedAged, 80 and overAmino Acid Transport System ASCFemaleHumansMaleMiddle AgedMinor Histocompatibility AntigensAmino Acid Transport System ASCImmunoconjugatesMinor Histocompatibility AntigensSLC1A5 protein, human

Identifiers

PMID38683495
PMCPMC11111564

What OpenQuestion holds

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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.