AVC-201 utilizes the RevCAR platform, an off-the-shelf allogeneic CAR-T technology that requires a bispecific target module (R-TM123) to activate CAR-T cells against CD123-expressing leukemia cells. This design enables clinicians to switch CAR-T activity on or off as needed, potentially improving safety when targeting antigens also expressed on normal tissues.

The completed Phase Ia dose-escalation study enrolled patients with R/R AML or MRD-positive AML who had exhausted standard treatment options.

Efficacy Outcomes-

• CAR-T cell expansion was superior to that observed with other published autologous and allogeneic CAR-Ts in AML, with peak levels exceeding 600,000 VCN copies/μg gDNA. 

• Repeated R-TM123 cycles triggered CAR-T reactivation. 

• Deep clinical responses were observed, e.g., among the 6 patients treated at the highest dose (DL15, 500M cells and 4.8mg/day of R-TM123), two morphological CRs with full blood count recovery (#13, #14), one MLFS in TP53-mutated AML (#17), and MRD conversions (#13, #14, #15).

Safety Outcomes-

• One DLT was observed: a Grade 2 IEC-HS (patient #12), successfully managed via on/off switch mechanism, Anakinra, and Dexamethasone. 

• No treatment-related mortality, neurotoxicity, or GvHD was reported. 

• CRS (Grade 1–3) occurred in 12 patients, with onset typically on Day 1. 

• Overall, the therapy was well tolerated.

KOL Insights-

“CD123 is a compelling target in AML because of its high prevalence and expression on both leukemic blasts and leukemic stem cells. At the same time, its presence on healthy hematopoietic progenitors presents a significant therapeutic challenge, as conventional CAR-T approaches may result in prolonged bone marrow aplasia. Future development will depend on strategies that can effectively target AML cells while minimizing toxicity to normal hematopoiesis.”– Expert Opinion

“The multi-layered gene-editing strategy is particularly innovative because it simultaneously addresses graft-versus-host disease and host immune rejection, two major challenges for allogeneic CAR-T therapy. By selectively modifying key immune recognition pathways while preserving HLA-B and HLA-C expression, this approach may enhance CAR-T persistence and feasibility, bringing the field closer to a truly scalable off-the-shelf cellular therapy platform.”– Expert Opinion

Conclusion-

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy with approximately 120,000–150,000 new cases diagnosed globally each year. Patients with relapsed/refractory AML face poor outcomes, with limited treatment options and median survival often measured in months. Despite the success of CAR-T therapies in B-cell malignancies, progress in AML has been hindered by antigen overlap between leukemic and healthy hematopoietic cells, creating significant safety concerns.

The Phase Ia RevSTAR-123 study provides the first clinical evidence that a switchable allogeneic CD123-directed CAR-T platform can be safely administered while generating meaningful anti-leukemic responses. The therapy demonstrated favorable tolerability, no treatment-related mortality or neurotoxicity, robust CAR-T expansion, and multiple CR-level responses in heavily pretreated patients. Importantly, the adapter-controlled mechanism enabled rapid CAR-T deactivation when needed, supporting a potentially safer approach to AML cell therapy. These findings establish an important proof-of-concept for switchable allogeneic CAR-T therapy and support ongoing Phase Ib development in relapsed/refractory AML.