Evidence map›Paper›PMID 38324336›Full record

ArticleMolecular cancer therapeutics2024

ADCT-602, a Novel PBD Dimer-containing Antibody-Drug Conjugate for Treating CD22-positive Hematologic Malignancies.

Francesca Zammarchi, Karin E Havenith, Nikoleta Sachini, Narinder Janghra, Simon Chivers, Esohe Idusogie, Eugenio Gaudio, Chiara Tarantelli, Francois Bertelli, Kathleen Santos and 8 more

Registry-linked trialOpen access · hybridAbstract read
In one paragraph

Article in Molecular cancer therapeutics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03698552 (A Phase I/II Study to Evaluate the Safety and Anti-Tumor Activity of ADCT-602 Targeting CD22 in Patients With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia), which is not on this map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
3.1field-weighted citation impact, top 7% of its field
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.

NCT03698552 phase1 / phase2terminatednot on this map

A Phase I/II Study to Evaluate the Safety and Anti-Tumor Activity of ADCT-602 Targeting CD22 in Patients With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia

TypeinterventionalSponsorM.D. Anderson Cancer CenterRan2018 to 2025Enrolled37ConditionsBlasts 5 Percent or More of Bone Marrow Nucleated Cells, CD22 Positive, Philadelphia Chromosome Positive, Recurrent B Acute Lymphoblastic LeukemiaArmsADCT-602
3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 11 citations in OpenAlex.

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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

18 authors at 7 institutions in 2 countries.

Francesca ZammarchiADC Therapeutics (UK) Ltd, London, United Kingdom.ORCID 0000-0001-9457-2170
Karin E HavenithADC Therapeutics (UK) Ltd, London, United Kingdom.ORCID 0000-0002-0610-4228
Nikoleta SachiniADC Therapeutics (UK) Ltd, London, United Kingdom.ORCID 0009-0007-3806-9686
Narinder JanghraADC Therapeutics (UK) Ltd, London, United Kingdom.ORCID 0000-0002-2816-8281
Simon ChiversADC Therapeutics (UK) Ltd, London, United Kingdom.ORCID 0009-0002-3916-3221
Esohe IdusogieADC Therapeutics America, Inc, Murray Hill, United States.ORCID 0009-0004-5324-6343
Eugenio GaudioInstitute of Oncology Research, Faculty of Biomedical Sciences, USI, Bellinzona, Switzerland.ORCID 0009-0006-6956-6135
Chiara TarantelliInstitute of Oncology Research, Faculty of Biomedical Sciences, USI, Bellinzona, Switzerland.ORCID 0000-0002-4394-7742
Francois BertelliAstraZeneca (MedImmune/Spirogen), London, United Kingdom.ORCID 0009-0006-3448-2089
Kathleen SantosAstraZeneca (MedImmune/Spirogen), London, United Kingdom.ORCID 0000-0002-0544-0975
Peter TyrerAstraZeneca (MedImmune/Spirogen), London, United Kingdom.ORCID 0000-0001-8004-5396
Simon CorbettUniversity College London, London, United Kingdom.ORCID 0009-0001-6166-1609
Filippo SprianoInstitute of Oncology Research, Faculty of Biomedical Sciences, USI, Bellinzona, Switzerland.ORCID 0000-0002-8615-1568
Gaetanina GolinoInstitute of Oncology Research, Faculty of Biomedical Sciences, USI, Bellinzona, Switzerland.ORCID 0009-0007-1035-8611
Luciano CascioneInstitute of Oncology Research, Faculty of Biomedical Sciences, USI, Bellinzona, Switzerland.ORCID 0000-0002-4606-0637
Francesco BertoniInstitute of Oncology Research, Faculty of Biomedical Sciences, USI, Bellinzona, Switzerland.ORCID 0000-0001-5637-8983
John A HartleyUniversity College London, London, United Kingdom.ORCID 0000-0003-3737-9897
Patrick H van BerkelADC Therapeutics (UK) Ltd, London, United Kingdom.ORCID 0000-0002-7315-0347
e-Therapeutics (United Kingdom) · GBInstitute of Oncology Research · CHAstraZeneca (United Kingdom) · GBCRUK Lung Cancer Centre of Excellence · GBAdc Therapeutics (Switzerland) · CHEnte Ospedaliero Cantonale · CHKing's College London · GB

Funding

ADC Therapeutics SA N/A
6 · The paper itself

Abstract

Relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) and lymphomas have poor patient outcomes; novel therapies are needed. CD22 is an attractive target for antibody-drug conjugates (ADCs), being highly expressed in R/R B-ALL with rapid internalization kinetics. ADCT-602 is a novel CD22-targeting ADC, consisting of humanized mAb hLL2-C220, site specifically conjugated to the pyrrolobenzodiazepine dimer-based payload tesirine. In preclinical studies, ADCT-602 demonstrated potent, specific cytotoxicity in CD22-positive lymphomas and leukemias. ADCT-602 was specifically bound, internalized, and trafficked to lysosomes in CD22-positive tumor cells; after cytotoxin release, DNA interstrand crosslink formation persisted for 48 hours. In the presence of CD22-positive tumor cells, ADCT-602 caused bystander killing of CD22-negative tumor cells. A single ADCT-602 dose led to potent, dose-dependent, in vivo antitumor activity in subcutaneous and disseminated human lymphoma/leukemia models. Pharmacokinetic analyses (rat and cynomolgus monkey) showed excellent stability and tolerability of ADCT-602. Cynomolgus monkey B cells were efficiently depleted from circulation after one dose. Gene signature association analysis revealed IRAK1 as a potential marker for ADCT-602 resistance. Combining ADCT-602 + pacritinib was beneficial in ADCT-602-resistant cells. Chidamide increased CD22 expression on B-cell tumor surfaces, increasing ADCT-602 activity. These data support clinical testing of ADCT-602 in R/R B-ALL (NCT03698552) and CD22-positive hematologic cancers.

Indexed as

Antineoplastic AgentsHematologic NeoplasmsImmunoconjugatesLymphoma, B-CellAnimalsHumansMacaca fascicularisRatsSialic Acid Binding Ig-like Lectin 2Antineoplastic AgentsCD22 protein, humanImmunoconjugatesSialic Acid Binding Ig-like Lectin 2

Identifiers

PMID38324336
PMCPMC10985467
OpenAlexW4391616786

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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.