Evidence map›Paper›PMID 35372008›Full record

ArticleFrontiers in oncology2022

Phase 1 Clinical Trial Evaluating the Safety and Anti-Tumor Activity of ADP-A2M10 SPEAR T-Cells in Patients With MAGE-A10+ Head and Neck, Melanoma, or Urothelial Tumors.

David S Hong, Marcus O Butler, Russell K Pachynski, Ryan Sullivan, Partow Kebriaei, Sarah Boross-Harmer, Armin Ghobadi, Matthew J Frigault, Ecaterina E Dumbrava, Amy Sauer and 15 more

2 registry-linked trialsOpen access · goldAbstract read
In one paragraph

Article in Frontiers in oncology, 2022. 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 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.0field-weighted citation impact, top 12% 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.

NCT02989064 phase1completednot on this map

Phase 1 Cell Dose Escalation Study to Assess the Safety and Tolerability of Genetically Engineered MAGE-A10ᶜ⁷⁹⁶T in HLA-A2+ Subjects With MAGE-A10 Positive Urothelial, Melanoma or Head and Neck Tumors

TypeinterventionalSponsorAdaptimmuneRan2016 to 2020Enrolled10ConditionsUrothelial Carcinoma, Head and Neck Cancer, Melanoma, Bladder Urothelial CarcinomaArmsAutologous genetically modified MAGE A10ᶜ⁷⁹⁶T cells
NCT03132922 phase1active not recruitingnot on this map

Phase 1 Dose Escalation, Multi-tumor Study to Assess the Safety, Tolerability and Antitumor Activity of Genetically Engineered MAGE-A4ᶜ¹º³²T in HLA-A2+ Subjects With MAGE-A4 Positive Tumors

TypeinterventionalSponsorUSWM CT, LLCRan2017 to 2032Enrolled71ConditionsUrinary Bladder Cancer, Melanoma, Head and Neck Cancer, Ovarian CancerArmsAutologous genetically modified MAGE-A4ᶜ¹º³²T cells, Autologous genetically modified MAGE-A4c1032T cells combined with low dose radiation
3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 19 citations in OpenAlex.

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  12. TCR engineered T cells for solid tumor immunotherapy.Experimental hematology & oncology · 2022
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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

25 authors at 6 institutions in 3 countries.

David S HongDepartment of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Marcus O ButlerPrincess Margaret Hospital Cancer Centre, University of Toronto, Toronto, ON, Canada.
Russell K PachynskiDivision of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States.
Ryan SullivanMassachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Partow KebriaeiDepartment of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Sarah Boross-HarmerPrincess Margaret Hospital Cancer Centre, University of Toronto, Toronto, ON, Canada.
Armin GhobadiDivision of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States.
Matthew J FrigaultMassachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Ecaterina E DumbravaDepartment of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Amy SauerAdaptimmune LLC, Philadelphia, PA, United States.
Francine BrophyAdaptimmune LLC, Philadelphia, PA, United States.
Jean-Marc NavenotAdaptimmune LLC, Philadelphia, PA, United States.
Svetlana FayngertsAdaptimmune LLC, Philadelphia, PA, United States.
Zohar WolchinskyAdaptimmune Limited, Abingdon, United Kingdom.
Robyn BroadAdaptimmune Limited, Abingdon, United Kingdom.
Dzmitry G BatrakouAdaptimmune LLC, Philadelphia, PA, United States.
Ruoxi WangAdaptimmune Limited, Abingdon, United Kingdom.
Luisa M SolisDepartment of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Dzifa Yawa DuoseDepartment of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Joseph P SandersonAdaptimmune Limited, Abingdon, United Kingdom.
Andrew B GerryAdaptimmune Limited, Abingdon, United Kingdom.
Diane MarksAdaptimmune LLC, Philadelphia, PA, United States.
Jane BaiAdaptimmune LLC, Philadelphia, PA, United States.
Elliot NorryAdaptimmune LLC, Philadelphia, PA, United States.
Paula M FracassoAdaptimmune LLC, Philadelphia, PA, United States.
Adaptimmune (United Kingdom) · GBThe University of Texas MD Anderson Cancer Center · USMassachusetts General Hospital · USWashington University in St. Louis · USPrincess Margaret Cancer Centre · CAUniversity of Toronto · CA

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 CA016672
6 · The paper itself

Abstract

Background: ADP-A2M10 specific peptide enhanced affinity receptor (SPEAR) T-cells are genetically engineered autologous T-cells that express a high-affinity melanoma-associated antigen (MAGE)-A10-specific T-cell receptor (TCR) targeting MAGE-A10-positive tumors in the context of human leukocyte antigen (HLA)-A*02. ADP-0022-004 is a phase 1, dose-escalation trial to evaluate the safety and anti-tumor activity of ADP-A2M10 in three malignancies (https://clinicaltrials.gov: NCT02989064). Methods: Eligible patients were HLA-A*02 positive with advanced head and neck squamous cell carcinoma (HNSCC), melanoma, or urothelial carcinoma (UC) expressing MAGE-A10. Patients underwent apheresis; T-cells were isolated, transduced with a lentiviral vector containing the MAGE-A10 TCR, and expanded. Patients underwent lymphodepletion with fludarabine and cyclophosphamide prior to receiving ADP-A2M10. ADP-A2M10 was administered in two dose groups receiving 0.1×10 Results: Ten patients (eight male and two female) with HNSCC (four), melanoma (three), and UC (three) were treated. Three patients were treated in each of the two dose groups, and four patients were treated in the expansion group. The most frequently reported adverse events grade ≥3 were leukopenia (10), lymphopenia (10), neutropenia (10), anemia (nine), and thrombocytopenia (five). Two patients reported cytokine release syndrome (one each with grade 1 and grade 3), with resolution. Best response included stable disease in four patients, progressive disease in five patients, and not evaluable in one patient. ADP-A2M10 cells were detectable in peripheral blood from patients in each dose group and the expansion group and in tumor tissues from patients in the higher dose group and the expansion group. Peak persistence was greater in patients from the higher dose group and the expansion group compared with the lower dose group. Conclusions: ADP-A2M10 has shown an acceptable safety profile with no evidence of toxicity related to off-target binding or alloreactivity in these malignancies. Persistence of ADP-A2M10 in the peripheral blood and trafficking of ADP-A2M10 into the tumor was demonstrated. Because MAGE-A10 expression frequently overlaps with MAGE-A4 expression in tumors and responses were observed in the MAGE-A4 trial (NCT03132922), this clinical program closed, and trials with SPEAR T-cells targeting the MAGE-A4 antigen are ongoing.

Indexed as

adoptive cellular therapyADP-A2M10HNSCCMAGE-A10melanomaTCRurothelial carcinoma

Identifiers

PMID35372008
PMCPMC8972123
OpenAlexW4220805673

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.