Clinical Summary:

• Design/Population: The phase 1a RevSTAR-123 study evaluated a switchable, allogeneic CD123-directed CAR T-cell therapy in heavily pretreated patients with either relapsed or refractory or MRD-positive acute myeloid leukemia expressing CD123 and lacking standard treatment options.
• Key Outcomes: The regimen showed favorable safety and tolerability, with no treatment-related mortality, neurotoxicity, or graft-versus-host disease. Robust CAR T-cell expansion and reactivation were observed with repeated adapter molecule dosing, and encouraging antileukemic activity was seen at higher dose levels, including complete remission-level responses and measurable residual disease conversion.
• Clinical Relevance: This switchable allogeneic CD123 CAR T-cell platform may offer a promising cellular therapy approach, with controllable activity and early evidence of meaningful responses supporting further dose optimization and clinical development.

Results from the phase 1a RevSTAR-123 study demonstrated that an investigational switchable allogeneic CD123-directed CAR T-cell therapy showed encouraging clinical activity and promising safety among heavily pretreated patients with relapsed or refractory acute myeloid leukemia (AML).

These results were presented by Martin Wermke, MD, University Hospital Carl Gustav Carus, Dresden, Germany, at the 2026 European Hematology Association (EHA) Congress in Stockholm, Sweden.

In this dose-escalation study, adult 17 patients with relapsed or refractory or measurable residual disease (MRD)-positive AML expressing CD123 on ≥20% of leukemic blasts with no remaining standard treatment options received lymphodepletion with fludarabine and cyclophosphamide over 3 days, followed by a single infusion of Allo-RevCAR01-T cells. The bispecific adapter molecule R-TM123 was administered as a continuous intravenous infusion during a 20-day induction cycle and subsequent 12-day consolidation cycles. Dose escalation evaluated 3 CAR-T dose levels (100× 10⁶, 250× 10⁶, and 500 × 10⁶ cells) in combination with escalating R-TM123 doses, followed by additional escalation of the adapter molecule at the highest CAR T-cell dose. 

Primary end points included safety, dose-limiting toxicities, and assessment of biologic and clinical activity.

At analysis, 1 dose-limiting incidence of grade 2 immune effector cell-associated hemophagocytic syndrome was reported, which was successfully managed through temporary CAR T-cell deactivation, anakinra, and dexamethasone. No treatment-related mortality, neurotoxicity, or graft-versus-host disease was reported. Cytokine release syndrome was reported in 12 patients and was grade ≤3. Overall, the treatment was considered well tolerated. 

Robust CAR-T expansion, with peak levels exceeding 600,000 vector copy number copies/μg genomic DNA. Repeated administration of R-TM123 triggered CAR T-cell reactivation and promoted continued expansion.

Among 6 patients treated at the highest dose level, 2 achieved morphological complete remission with full blood count recovery, 1 patient with TP53-mutated AML achieved a morphologic leukemia-free state, and MRD conversion occurred in 3 patients. Responses were ongoing. 

At the 2 highest dose levels combined, 4 of 8 patients achieved complete remission-level response and 3 achieved MRD conversion. 

This switchable, allogeneic CAR-T showed favorable safety and tolerability without treatment-related mortality or neurotoxicity,” concluded Dr Wermke. “RevSTAR-123 has now advanced into Phase Ib, enrolling 20 patients at DL15.” 

Source:

Wermke M, Jongen-lavrencic M, Metzelder S, et al. First-in-class switchable allogeneic CAR-T therapy for CD123+ AML – results from the phase 1a REVSTAR-123 (AVC-201-01) study. Presented at EHA Congress. June 11 - June 14, 2026. Stockholm, Sweden. Abstract EHA-7241