John F. DiPersio presented at the 60th American Society of Hematology Annual Meeting & Exposition, data from a phase I/II study of flotetuzumab, a CD123 x CD3 bispecific dual-affinity re-targeting (DART®) molecule, in patients with relapsed or refractory (R/R) acute myeloid leukemia (AML). Flotetuzumab is a humanized DART® molecule that is generated from antibodies to CD3 and CD123. Flotetuzumab acts to redirect T-cells via CD3 to target blast cells expressing CD123. This interaction can mediate, target-effector cell association, T-cell activation, proliferation and receptor diversification.
In this phase I/II study, the safety and preliminary clinical activity of flotetuzumab were assessed in 31 patients (median age = 64.0 years; range, 29.0–82.0) with R/R AML. Of these enrolled patients, 19 (61.3%) had primary refractory disease. Patients received a lead-in dose (30 ng/kg/day for 3 days followed by 100 ng/kg/day for 4 days) during week 1, followed by flotetuzumab at the recommended phase 2 dose, 500 ng/kg/d during week 2–4 of cycle 1. In cycle 2 and beyond, patients received flotetuzumab on a 4-day on/3-day off regimen.
- Most common adverse events were infusion-related reaction (IRR)/cytokine release syndrome (CRS)
- Grade ≥ 3 IRR/CRS occurred in 12.9% of patients (4/31)
- Most IRR/CRS events were of short duration and reversible with protocol-specified supportive care
- Antileukemic activity was reported in 67% (18/27) of response-evaluable patients
- Overall response rate (ORR): 25.9% (7/27)
- Complete response (CR)/ CR with incomplete blood count (CRi) rate of 18.5% (5/27)
- Median duration of response: 3 months (range, 1.1–5.6 months)
- Response to flotetuzumab was distinct in patients with relapsed disease compared to those who were refractory to standard induction chemotherapy
- ORR in patients with relapsed or refractory disease: 35.3% (6/17) vs3% (1/7)
- CR rate in patients with relapsed or refractory disease: 29.4% (5/17) vs 0% (0/7)
- Compared to relapsed patients, expression of inflammatory genes (P = 0.026) and increased CD123 density was observed in patients with refractory AML
In conclusion, the speaker noted that flotetuzumab demonstrated “antileukemic activity with an acceptable safety profile, in particular, among refractory patients, a difficult-to-treat patient population that represents a significant area of unmet medical need.”