AbbVie takes pivekimab pivotal

AbbVie, awaiting FDA approval for its CD123-targeting ADC pivekimab sunirine in a rare cancer, will soon start its first pivotal study of the project in a more familiar setting. The phase 2/3 Revival trial will test the asset, alongside Venclexta and azacitidine, in first-line AML patients unfit for intensive chemotherapy, a new listing on clinicaltrials.gov has revealed.First-line AML is also being targeted by menin inhibitors from the likes of Syndax, Kura and Johnson & Johnson. AbbVie is taking a different tack by gunning specifically for CD123-positive disease, but this is still a large proportion of the AML population; around 50-75% of patients, depending on the cutoffs used.Pivekimab plus ven/aza has produced promising response rates in first-line AML in a phase 1/2 trial, but two adverse event-related deaths were also seen among 49 patients. Broadly, targeting CD123 has been linked with toxicity, so AbbVie might need to tread carefully.CD123 Revival?The Revival study, due to start in July, will have two phases, both comparing pivekimab plus ven/aza, versus ven/aza alone. The open-label phase 2 part will primarily evaluate complete response rate, while the double-blind phase 3 portion will measure this as well as overall survival.Presumably this structure will allow AbbVie to ascertain early whether there’s indeed a benefit with pivekimab.In a phase 1/2 study presented at ASH last year, there was a 63% complete response rate among 49 first-line unfit patients treated with pivekimab plus ven/aza. Median overall survival was 12.4 months, and TP53 wild type patients did better on this metric.However, three patients discontinued due to adverse events of myocardial infarction, soft tissue infection and thrombocytopenia, and there were two deaths, due to respiratory failure and pancytopenia – a decrease in all three types of blood cells.Targeting CD123 has been associated with toxicity and clinical holds, and discontinued assets with this mechanism include AstraZeneca’s ADC lixarkitug samrotecan (AZD9829), Xencor's MAb vibecotamab, and Car-T projects from Novartis (JEZ567) and Cellectis (UCART123).Pivekimab is currently the most advanced industry project taking aim at this target, and the only ADC, according to OncologyPipeline.AbbVie filed pivekimab with the FDA last September in blastic plasmacytoid dendritic cell neoplasm, a very rare blood cancer, based on the phase 1/2 Cadenza trial. The company hasn’t disclosed whether the submission has been accepted, but has said that a decision is expected sometime in 2026.The asset came via the $10bn takeout of ImmunoGen in 2023, which was primarily driven by the folate receptor alpha (FRα) ADC Elahere. Selected studies of pivekimab sunirineTrialSettingRegimenNotePh1/2 Cadenza1st-line & r/r CD123+ve BPDCNMonoRx, uncontrolledFiled with FDA in BPDCN in Sept 2025; decision due in 2026Ph1/2 IMGN632-08021st-line & r/r CD123+ve AML+ ven/azaData at ASH 2025 in 1st-line unfit pts: 63% CR; 2 AE-related deathsPh2/3 Revival1st-line & r/r CD123+ve AML (intensive chemo ineligible)+ ven/azaTo start Jul 2026Note: BPDCN=blastic plasmacytoid dendritic cell neoplasm. Source: OncologyPipeline.