Pivekimab Sunirine Plus Azacitidine and Venetoclax Shows Promise

In a phase 1b/2 trial, the combination of pivekimab sunirine, a CD123-targeted antibody-drug conjugate (ADC), with azacitidine and venetoclax produced responses in patients with high-risk, CD123-positive, newly diagnosed or relapsed/refractory AML.3 

Patients enrolled in the trial (ClinicalTrials.gov Identifier: NCT04086264) received treatment in a 3-drug escalation over a 28-day cycle — pivekimab sunirine at 0.015 mg/kg or 0.045 mg/kg on day 7, azacitidine at 50 mg/kg2 or 75 mg/m2 on days 1-7, and venetoclax at 400 mg for 8, 14, or 21 days. 

Continue Reading

The trial included 10 patients with newly diagnosed AML. All of them received the recommended phase 2 dosing schedule, which was pivekimab sunirine at 0.045 mg/kg on day 7, azacitidine at 75 mg/m2 on days 1-7, and venetoclax for 14 days.

Five of these patients achieved a CR, and 1 achieved a partial response. Five patients were still on treatment at last follow-up, 1 patient went on to allo-HSCT, and 1 patient died within 60 days.

There were 91 patients with relapsed/refractory AML. In this group, the overall response rate (ORR) was 45%, and the CR rate was 13%. The rate of composite complete remission (CCR; CR plus CRi and CR with partial hematologic recovery or incomplete platelet recovery) was 25%. The median duration of CCR was 7.7 months.

Among the 37 patients with relapsed/refractory disease who received the recommended phase 2 dosing schedule, the ORR was 38%, the CCR rate was 22%, and the CR rate was 14%. The ORR was 53% in venetoclax-naïve patients and 36% in patients who had prior venetoclax treatment. The CRR rate was 38% and 11%, respectively.

The most common treatment-emergent AEs in the relapsed/refractory cohort were febrile neutropenia (33%), thrombocytopenia (23%), dyspnea (22%), infusion-related reactions (22%), hypokalemia (21%), and fatigue (20%). Five percent of patients discontinued treatment due to pivekimab sunirine-related AEs. There were no treatment-related deaths.

There were no cases of tumor lysis syndrome, veno-occlusive disease, capillary leak syndrome, or cytokine release syndrome, said study presenter Naval Daver, MD, of The University of Texas MD Anderson Cancer Center in Houston. 

That finding makes pivekimab “a very attractive CD123-targeting ADC,” he said. 

“This drug potentially opens up another therapeutic option for relapsed/refractory AML patients who have limited treatment options, particularly if they have not been treated with venetoclax in the past,” said Jun Choi, MD, of NYU Langone’s Perlmutter Cancer Center in New York, New York, who was not involved in this study. “Further trials with larger patient populations are warranted.”

As this was not a randomized study, “it remains to be seen if any additional toxicity for the combination outweighs the benefits seen over hypomethylating agents and venetoclax alone,” said Dr Gerds, who was not involved in the study.