AVC-203 Achieves Trial Approval from FDA, EMA for R/R B-Cell Lymphoma

A phase 1/2 clinical trial examining the CRISPR-engineered allogeneic chimeric antigen receptor (CAR)-T candidate AVC-203 (QUADvance) has been approved by the FDA and the European Medicines Agency (EMA) for the treatment of patients with relapsed/refractory (R/R) B-cell malignancies.¹

AVC-203 is designed to target and eliminate cells expressing receptors CD19 and/or CD20. In addition to dual-antigen targeting, AVC-203 is engineered to enable donor cells to avoid graft-vs-host disease and rejection by the patient's immune system.

"We are excited to build on the early success and promising activity and safety of our ongoing clinical program [NCT05949125] of allogeneic CAR-T in [acute myeloid leukemia] by now advancing into B-cell lymphoma with what we believe to be the most scientifically compelling allogeneic technology in the industry," said Andrew Schiermeier, president and CEO of AvenCell Therapeutics, developer of AVC-203, in a news release. "To date, attempts at solving the key scalability and cost issues of autologous CAR-T therapy by engineering cells from unrelated donors have fallen short. Nevertheless, the obvious benefits of such an approach, including consistency and potency of an actual drug product - something in vivo approaches cannot provide - remain as compelling as ever. AvenCell remains focused on ensuring that any patient who can benefit from CAR-T therapy can receive it, through the massive scaling of supply and dramatic reductions in cost of goods, with a product that is as good or better than best-in-class autologous CAR-Ts."

The newly approved phase 1/2 study will be conducted across multiple sites in the US and Europe. The phase 1a dose-escalation study is expected to be followed by a phase 1b dose-expansion study, and eventually a phase 2 trial.

About the Ongoing Phase 1 Study

The ongoing phase 1 study is evaluating the combination of allogeneic human T-cell genetically multi-edited and expressing a reversed, universal chimeric antigen receptor (RevCAR) with a recombinant antibody derivative (R-TM123), referred to as Allo-RevCAR01-T-CD123. Patients with R/R AML with selected CD123-positive hematologic malignancies are included in the study.²

Dose escalation reached dose level 12 (500 million Allo-RevCAR01-T cells plus 2.4 mg/day dose of R-TM123). Higher dose levels remain under investigation. A total of 10 patients have received the induction treatment cycle, and 3 patients have completed at least 1 consolidation cycle.

The median age of patients is 62.5 years (range, 43–74). The trial enrolled a heavily pretreated patient cohort with a median of 5.5 prior lines of therapy. Of the 10 patients treated, 5 were classified as adverse risk and 5 were classified as intermediate risk at the time of screening.

No dose-limiting toxicities or treatment-related adverse events beyond grade 2 have been observed to date, regardless of patient age or prior treatment intensity. Cytokine release syndrome was reported in 6 patients, all grade 1 or 2.

REFERENCES

1.AvenCell Therapeutics announces IND clearance and EMA approval of clinical trial application (CTA) for the QUADvance study, a phase I/II trial evaluating AVC-203, a novel allogeneic CD19/CD20 CAR-T investigational therapy for the treatment of relapsed/refractory B-cell malignancies. News release. AvenCell. Published December 4, 2025. Accessed December 9, 2025. https://tinyurl.com/3feap44m

2.Wermke M, Westermann J, Metzelder S, et al. Allogeneic CAR-T therapy AVC-201 in AML positive for CD123. Published November 3, 2025. Accessed December 9, 2025. Blood (2025) 146 (Supplement 1): 3426. doi: 10.1182/blood-2025-3426.