Meyer, Tim;
Finn, Richard S;
Borad, Mitesh;
Mahipal, Amit;
Edeline, Julien;
Houot, Roch;
Hausner, Petr F;
... Sangro, Bruno; + view all
(2025)
Phase I trial of ADP-A2AFP TCR T-cell therapy in patients with advanced hepatocellular or gastric hepatoid carcinoma.
Journal of Hepatology
10.1016/j.jhep.2025.07.033.
(In press).
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Abstract
Background & Aims: Patients with advanced hepatocellular carcinoma (HCC) generally experience poor outcomes despite current therapies; alternative treatments are needed. 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 that progressed on, were intolerant to, or refused prior systemic therapy. Participants received lymphodepletion chemotherapy (cyclophosphamide 500 mg/m2/day for 3 days and fludarabine 20 mg/m2/day for 3 days, or cyclophosphamide 600 mg/m2/day for 3 days and fludarabine 30 mg/m2/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 1 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 duration of stable disease ≥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.
| Type: | Article |
|---|---|
| Title: | Phase I trial of ADP-A2AFP TCR T-cell therapy in patients with advanced hepatocellular or gastric hepatoid carcinoma |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.jhep.2025.07.033 |
| Publisher version: | https://doi.org/10.1016/j.jhep.2025.07.033 |
| Language: | English |
| Additional information: | © 2025 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
| Keywords: | Adoptive T-cell therapy, hepatocellular carcinoma, T-cell receptor T-cell therapy, immunotherapy, alpha-fetoprotein |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10212387 |
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