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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.
Meyer, T.
Finn, R. S.
Borad, M.
Mahipal, A.
Edeline, J.
Houot, R.
Hausner, P. F.
Hollebecque, A.
Goyal, L.
Frigault, M.
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. Clinicaltrials.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. H.
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.
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. H.
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.
Description
Date
2026
Publisher
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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. 2026 JAN;84(1).