Cusatuzumab + azacitidine in AML: Results from the phase II CULMINATE trial

Cusatuzumab, an anti-CD70 antibody, has demonstrated efficacy at doses ≥10 mg/kg in combination with azacitidine in patients with newly diagnosed acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy in a phase I/II trial.¹ However, there were no dose-limiting toxicities associated with cusatuzumab across the dosing range of 1–20 mg/kg in this trial, raising the need to identify the optimal dose.¹

The multicenter, randomized, phase II CULMINATE trial (NCT04023526) assessed the safety and efficacy of two dose levels of cusatuzumab, 10 mg/kg and 20 mg/kg, plus azacitidine in this patient population.¹ Here, we summarize results from part 1 of the CULMINATE trial published by Pabst et al.¹ in The Lancet Haematology

Study design and patient population¹

• Part 1 of the CULMINATE trial was a randomized study to identify the optimal dose of cusatuzumab.

• Patients received either 10 mg/kg or 20 mg/kg intravenously on Days 3 and 17, plus azacitidine 75 mg/m² on Days 1–7, in 28-day cycles.
• The primary endpoint was complete remission.
• In part 1, 103 patients across 40 centers were enrolled.

• Part 2 of the CULMINATE trial was a single-arm expansion to evaluate cusatuzumab plus azacitidine at the optimal dose identified in part 1.

• Part 2 was not initiated due to venetoclax plus azacitidine becoming the new standard of care based on results from the VIALE-A trial.

Key findings¹

• The complete remission rates were 12% and 27% in the 10 mg/kg group and 20 mg/kg group, respectively (Figure 1).
• In total, 99% of all patients had ≥1 treatment-emergent adverse event (TEAE), and 55% of patients experienced treatment-related TEAEs.
• Grade ≥3 TEAEs were observed in 99% of all patients, including thrombocytopenia (52%), anemia (40%), neutropenia (39%), leucopenia (28%), and pneumonia (25%).
• Serious TEAEs occurred in 86% of patients in the 10 mg/kg group and 78% of patients in the 20 mg/kg group.
• Overall, 35% and 31% of patients died due to TEAEs in the 10 mg/kg group and 20 mg/kg group, respectively.

CR, complete remission; CRh, CR with partial hematological recovery; CRi, CR with incomplete hematological recovery; MLFS, morphological leukemia-free state; NE, not evaluable; ORR, overall response rate; PD, progressive disease; PR, partial remission; SD, stable disease.
*Data from Pabst, et al.¹

Key learnings

Based on the efficacy and safety results from this trial, the recommended dose of cusatuzumab in combination with azacitidine is 20 mg/kg. Future studies, such as the phase I ELEVATE trial (NCT04150887), will investigate the triplet combination of cusatuzumab plus venetoclax and azacitidine.