Item

Phase I trial of ADP-A2AFP TCR T-cell therapy in patients with advanced hepatocellular or gastric hepatoid carcinoma

Meyer, T.
; 
Finn, R. S.
; 
Borad, M.
; 
Mahipal, A.
; 
Edeline, J.
; 
Houot, R.
; 
Hausner, P. F.
; 
Hollebecque, A.
; 
Goyal, L.
; 
Frigault, M.
... show 10 more
Citations
Google Scholar:
Lookup
Altmetric:
Abstract
BACKGROUND & AIMS: Patients with advanced hepatocellular carcinoma (HCC) generally experience poor outcomes despite current therapies, necessitating the development of alternative treatments. ADP-A2AFP is an investigational autologous T-cell therapy with an affinity-enhanced T-cell receptor (TCR) targeting alpha-fetoprotein (AFP). METHODS: We describe a phase I, open-label, first-in-human clinical trial of ADP-A2AFP (NCT03132792) in human leukocyte antigen-eligible participants with AFP-expressing HCC (or other tumor) not amenable to transplant/resection who progressed on, were intolerant to, or refused prior systemic therapy. Participants received lymphodepletion chemotherapy (cyclophosphamide 500 mg/m(2)/day for 3 days and fludarabine 20 mg/m(2)/day for 3 days, or cyclophosphamide 600 mg/m(2)/day for 3 days and fludarabine 30 mg/m(2)/day for 4 days) followed by ADP-A2AFP intravenous infusion. Safety evaluation was the primary objective; response per RECIST v1.1 was the key secondary endpoint. RESULTS: Twenty-one participants, 20 with advanced HCC and one with gastric hepatoid carcinoma received ≥1 ADP-A2AFP infusion. All participants experienced ≥1 grade 3 or higher adverse event; 52.4% experienced ≥1 grade 3 or higher event considered related to ADP-A2AFP treatment. Six participants experienced cytokine release syndrome (grade 1-2: n = 5; grade 4: n = 1). Best overall responses were complete response (n = 1), partial response (n = 1), and stable disease (n = 12); overall response rate was 9.5%. Eight patients had a stable disease duration of ≥16 weeks. Infiltration of ADP-A2AFP TCR and CD8+ T cells was seen in AFP-positive areas of post-treatment tumor samples. A relationship was demonstrated between increased ADP-A2AFP dose and serum AFP reduction in responders. CONCLUSIONS: Lymphodepletion chemotherapy followed by ADP-A2AFP TCR T-cell therapy showed a manageable safety profile and preliminary indications of antitumor activity in these previously treated patients. IMPACT AND IMPLICATIONS: Adoptive T-cell therapy could be a much-needed additional treatment strategy for advanced hepatocellular carcinoma. Clinicians and researchers interested in the development of adoptive T-cell therapies for advanced solid tumors will be interested to learn that in this phase I trial, ADP-A2AFP T-cell receptor T-cell therapy was associated with an acceptable benefit-to-risk profile and encouraging antitumor activity, illustrating the treatment potential of adoptive T-cell therapy for advanced hepatocellular carcinoma. GOV NUMBER: NCT03132792; first posted 2017-04-08.
Authors
Meyer, T.
Finn, R. S.
Borad, M.
Mahipal, A.
Edeline, J.
Houot, R.
Hausner, P. F.
Hollebecque, A.
Goyal, L.
Frigault, M.
Evans, T. R. J.
Wong, K. M.
Tan, B. R.
Mitry, E.
Sarker, D.
Feun, L.
El-Rayes, B.
Thistlethwaite, F.
Kaseb, A.
Alese, O.
Jin, Z.
Cirillo, C.
Bruix, J.
Roddie, C.
Noto, P.
Fayngerts, S.
Cristiani, S.
Sampson, J.
Bai, J.
Isabelle, M.
Broad, R.
Sun, A.
Norry, E.
Sangro, B.
Affiliation
University College London, London, UK. Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USA. Mayo Clinic, Phoenix, AZ, USA. Mayo Clinic, Rochester, MN, USA; University Hospitals Seidman Cancer Center, Cleveland, OH, USA. Centre Eugène-Marquis, Rennes, France. Department of Hematology, University Hospital of Rennes, University of Rennes, Rennes, France. University of Maryland, Baltimore, MD, USA. Institut de Cancérologie Institut Gustave Roussy, Villejuif, France. Massachusetts General Hospital Cancer Center, Boston, MA, USA. University of Glasgow, Beatson West of Scotland Cancer Centre, Glasgow, UK. University of Washington/Seattle Cancer Care Alliance, Seattle, WA, USA. Washington University School of Medicine, St. Louis, MO, USA. Paoli-Calmettes Institute, Marseille, France. King's College London, London, UK. Sylvester Comprehensive Cancer Center, Miami, FL, USA. Emory University School of Medicine, Atlanta, GA, USA. The Christie NHS Foundation Trust and University of Manchester, Manchester, UK. The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Mayo Clinic, Rochester, MN, USA. Adaptimmune, Philadelphia, PA, USA. BCLC Group, Network for Biomedical Research Center for Hepatic and Digestive Diseases (CIBEREHD), Hospital Clinic, IDIBAPS, Barcelona, Spain. Adaptimmune, Abingdon, Oxfordshire, UK. Adaptimmune, Philadelphia, PA, USA. Electronic address: ecnorry@gmail.com. Clinica Universidad de Navarra and CIBEREHD, Pamplona, Spain.
Description
Date
2025
Publisher
Collections
All Christie Publications
Show all metadata
Keywords
Type
Article
Citation
Meyer T, Finn RS, Borad M, Mahipal A, Edeline J, Houot R, et al. Phase I trial of ADP-A2AFP TCR T-cell therapy in patients with advanced hepatocellular or gastric hepatoid carcinoma. Journal of hepatology. 2025 Aug 12. PubMed PMID: 40812667. Epub 2025/08/14 22:51. eng.
Journal Title
Journal ISSN
Volume Title
URI
https://christie.openrepository.com/handle/10541/627984
Embedded videos