Outcomes of CD20-targeting CAR T-cell therapy in patients with advanced melanoma: MB-CART20.1 Melanoma phase I trial.

Authors

Hyatt Balke-Want, Sebastian Theurich, Philipp Gödel, Stefanie Biedermann, Nicole Kreuzberg, Peter Borchmann, Danmei Zhang, Lena Weiss, Klara Dorman, Veit Bücklein, Marion Subklewe, Dirk Tomsitz, Lucie Heinzerling, Florentine Pia Altefrohne, Christine Schubert, Linda Hanssens, Liang Gao, Anders Wennborg, Heinz Haverkamp, Michael Apel, Tatjana Holzer, Ben Novak, Max Schlaak, Hinrich Abken, Nadine Kutsch, Michael von Bergwelt-Baildon

Published in

European journal of cancer (Oxford, England : 1990). Volume 249. Pages 117780. Oct 17, 2026. Epub Oct 17, 2026.

Abstract

Previous studies identified CD20⁺ cells within the melanoma tumor microenvironment, including tumor-associated B-cells and putative cancer stem cells (CSC), as potential therapeutic targets. We therefore evaluated CD20-targeting CAR T-cells in patients with advanced melanoma.
This prospective, open-label phase I trial evaluated a 3 +3 design in patients with advanced melanoma, refractory to approved treatments, to assess safety and preliminary activity of autologous anti-CD20 CAR T-cells (MB-CART20.1). Following lymphodepleting chemotherapy, patients received a single MB-CART20.1 infusion. Primary endpoints were safety and tolerability; secondary endpoints included kinetics and early evidence for antitumor activity. Three patients received dose level 1 (DL1) (1.0 ×10⁵ cells/kg) and four patients DL2 (1.0 ×10⁶ cells/kg).
No DLTs occurred at DL1, while two patients experienced DLTs at DL2 (grade 3 ICANS and grade 4 hepatotoxicity). Overall, 43 serious TEAEs were reported across all seven patients. Stable disease was observed in three patients at week 16; all had progressed by month 6. All had received immune checkpoint inhibitors within 6 months before leukapheresis and showed reduced exhaustion marker expression on CD8⁺ T-cells. In addition, the frequency of CD19⁺CD24⁺CD27⁺ B_reg cells trended to associate with progressive disease and inversely correlate with toxicity. MB-CART20.1 showed robust in vivo expansion however, severe DLTs at DL2 without durable clinical benefit led to early trial termination.
In advanced melanoma, MB-CART20.1 was associated with marked expansion and toxicity, suggesting that B_reg depletion and the melanoma-typical treatment history might have driven distinct CAR T-associated immunotoxicities.

PMID:
42913258
Bibliographic data and abstract were imported from PubMed on 24 Oct 2026.

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