Safety and efficacy of pivekimab sunirine in R/R AML: phase I/II study

CD123 is commonly overexpressed in patients with acute myeloid leukemia (AML).¹ Pivekimab sunirine is a novel antibody-drug conjugate comprising a high affinity CD123 antibody.¹

Here, we summarize the results from a phase I/II dose escalation and dose expansion trial (NCT03386513) investigating the safety and antileukemic activity of pivekimab sunirine in relapsed/refractory AML published by Daver et al.¹ in The Lancet Oncology.

Study design¹

• The dose escalation phase followed a 3 + 3 dose design.
  • In Schedule A, dosing started at 0.015 mg/kg of pivekimab sunirine and escalated five times to 0.45 mg/kg.
  • In Schedule B, dosing started at 0.015 mg/kg of pivekimab sunirine and escalated twice to 0.060 mg/kg. However, Schedule B was not pursued further.
• In the dose expansion phase, two doses from Schedule A were selected (0.045 mg/kg and 0.090 mg/kg).
• The primary endpoints of the trial were the maximum tolerated dose and the recommended phase II dose (RP2D) of pivekimab sunirine.
• Secondary endpoints included safety and antileukemic activity.

Key findings¹

• A total of 68 patients were enrolled in Schedule A at a median follow-up of 46.32 months.
  • 38 patients in the dose-escalation phase.
  • In the dose-expansion phase, 20 patients received 0.045 mg/kg and 10 patients received 0.090 mg/kg.
• The selected RP2D was 0.045 mg/kg once every 3 weeks; 29 patients received RP2D of pivekimab sunirine.

Safety

• During dosing Schedule A, there were three dose-limiting toxicities.
  • The most common Grade ≥3 treatment-emergent adverse events were febrile neutropenia (35%), and pneumonia (28%).
  • The most common Grade ≥3 treatment-related adverse event (TRAE) was febrile neutropenia (13%).
  • The 30-day mortality rate was 7%.
  • No dose-limiting toxicity-based maximum tolerated dose was reached.
• During the RP2D, treatment-emergent adverse events occurred in 97% of patients with the most common Grade ≥3 event being febrile neutropenia (Figure 1).
  • The most common Grade ≥3 TRAEs were febrile neutropenia (10%), infusion-related reactions (7%), and anemia (7%).
  • There were no deaths due to TRAEs.

Figure 1. A TEAEs Grade ≥3 and B serious TEAEs occurring in ≥5% of patients treated with the RP2D of pivekimab sunirine * 

RP2D, recommended phase II dose; TEAE, treatment-emergent adverse event.
*Adapted from Daver, et al.¹

Efficacy

• At RP2D, the overall response rate was 21% and the composite complete remission rate was 17% (Table 1).

Table 1. Efficacy endpoints of patients enrolled in dosing Schedule A and those treated with the RP2D of pivekimab sunirine *