An open-label, multicenter, phase 1b study (ELEVATE) evaluated the safety and efficacy of the anti-CD70 monoclonal antibody cusatuzumab in combination with venetoclax plus azacitidine in patients with untreated acute myeloid leukemia (AML) who are not eligible for intensive chemotherapy.
The study enrolled patients with previously untreated AML (de novo or secondary) who were ineligible for intensive chemotherapy due to age ≥75 years or medical comorbidities. Eligible patients received cusatuzumab (10 or 20 mg/kg intravenously, day 3 and day 17), venetoclax (3-day ramp-up with 100, 200, and 400 mg orally; 400 mg daily dosing thereafter), and azacitidine (75 mg/m2 subcutaneously or intravenously, days 1-7) in 28-day cycles. The primary objective was assessment of safety and tolerability of the triplet combination; key secondary objectives were response rate and time to response.
A total of 44 patients were enrolled in the study. The median age of the study cohort participants was 75 years; 36.4% had secondary AML, 40.9% had an Eastern Cooperative Oncology Group performance status of 2; 20.5% had intermediate European LeukemiaNet risk, and 61.4% had adverse European LeukemiaNet risk. Of 44 patients, 41 received a starting dose of 20 mg/kg cusatuzumab, and 3 patients received a starting 10-mg/kg dose with the option to escalate to 20 mg/kg (1 patient escalated to 20 mg/kg).
Grade ≥3 treatment-emergent adverse events (TEAEs) were reported in 97.7% of the patients; the most common TEAEs occurring in ≥10% of patients were neutropenia (68.2%), thrombocytopenia (65.9%), febrile neutropenia (36.4%), anemia (34.1%), leukopenia (29.5%), sepsis (27.3%), and lymphopenia (15.9%). Serious TEAEs were reported in 75% of patients; the most common that occurred in ≥5% of patients were febrile neutropenia (27.3%), sepsis (22.7%), COVID-19 (6.8%), and thrombocytopenia (6.8%). Grade ≥3 serious TEAEs were reported in 72.7% of the patients. Infusion-related reactions were reported in 11.4% of patients. Treatment discontinuations due to adverse events (AEs) were reported in 6 (13.6%) patients; deaths due to AEs were reported in 5 (11.4%) patients. The mortality rate within 30 days and 60 days from start of treatment was 4.5% (2 deaths) and 6.8% (3 deaths), respectively.
At a median follow-up of 40 weeks, a complete remission (CR) rate of 47.7% was achieved in the intent-to-treat population (n = 44); CR/CR with incomplete hematologic recovery (CRi) rate was 77.3%; CR with partial hematologic recovery (CRh) rate was 20.5%; morphologic leukemia-free state (MLFS) was achieved in 11.4% of patients. Of the 34 responders who achieved CR/CRh/CRi, 47.7% were minimal residual disease negative by flow cytometry at or after achievement of response; median time to first response was 4.21 (3.0-25.0) weeks. In the post-hoc response evaluable population (n = 42; excluded 2 patients who died before first evaluation), CR rate was 50%, CR/CRi rate was 81.0%, and MLFS was 11.9%. Dose delays were experienced by 97.1% of responders. Six patients underwent allogeneic stem-cell transplantation and remain alive at data cutoff.
Based on these preliminary results, it was concluded that the addition of cusatuzumab to current standard-of-care venetoclax/azacitidine was generally well-tolerated and showed promising antileukemic activity in elderly patients with untreated AML.
Source: Roboz GJ, et al. ASH 2021; abstr 369.