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

Jan 31, 2024
Learning objective: After reading this article, learners will be able to cite a new development in the treatment of acute myeloid leukemia.

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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.

Figure 1. Response rates by dose level in the CULMINATE trial* 

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.

  1. Pabst T, Papayannidis C, Demirkan F, et al. Cusatuzumab plus azacitidine in newly diagnosed acute myeloid leukaemia ineligible for intensive chemotherapy (CULMINATE): part one of a randomised, phase 2, dose optimisation study. Lancet Haematol. 2023;10(11):e902-e912. DOI: 10.1016/S2352-3026(23)00207-7


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