Abstract
[ 225 Ac]Ac-AKY-1189, a Nectin-4 targeted radiopharmaceutical, in patients with previously treated locally advanced or metastatic solid tumors: Phase 1b Nectinium-2 study
Journal of clinical oncology, Vol.44(7_suppl), TPS902
03/2026
DOI: 10.1200/JCO.2026.44.7_suppl.TPS902
Abstract
TPS902 Background: Nectin-4 is a clinically validated target in metastatic urothelial cancer and is over-expressed in multiple additional solid tumor types suggesting a broad therapeutic potential. AKY-1189 is a high affinity and selective Nectin-4 targeted miniprotein which is rapidly cleared from plasma and shows a favorable normal tissue biodistribution in humans when conjugated to 68 Ga (Sathekge et al, 2024). [ 225 Ac]Ac-AKY-1189 is under development for the treatment of patients with locally advanced or metastatic solid tumors. [ 225 Ac]Ac-AKY1189 has been shown to induce regression and stasis in preclinical models of urothelial carcinoma after a single administration. Target-dependent efficacy of the radiopharmaceutical is observed at well-tolerated dosages. Available data support investigating the efficacy and safety of [ 225 Ac]Ac-AKY-1189 in a clinical study. Methods: The NECTINIUM-2 (NCT07020117) study is a first in human, phase 1b, 2-part (dose escalation and dose expansion), multi-center, open-label study of [ 225 Ac]Ac-AKY-1189. Key inclusion criteria are age ≥18 years; histologically or cytologically confirmed locally advanced or metastatic solid tumors; ≥1 measurable lesion per RECIST v1.1; ECOG of 0 or 1; adequate end-organ function; documented progression on prior lines of chemotherapy in the metastatic setting; and tumor uptake on a [ 64 Cu]Cu-AKY-1189 PET/CT scan. Key exclusion criteria are prior radiopharmaceutical therapy; investigational treatment in the past 4 weeks; and anticancer therapy or external beam radiotherapy in the past 3 weeks. The Part 1 dose escalation will investigate ascending doses of [ 225 Ac]Ac-AKY-1189 (up to 6 cycles) in ~30 patients with locally advanced or metastatic urothelial cancer. The aim of Part 1 is to determine the maximum tolerated dose (MTD) or maximum administrated dose (MAD) and the recommended Part 2 dose (RP2D) of [ 225 Ac]Ac-AKY-1189. Once RP2D is established, part 2 will evaluate the clinical activity of [ 225 Ac]Ac-AKY-1189 in 3 cohorts of patients with Nectin-4 positive solid tumors. NECTINIUM-2 has started enrolling subjects in the United States. Clinical trial information: NCT07020117 .
Details
- Title: Subtitle
- [ 225 Ac]Ac-AKY-1189, a Nectin-4 targeted radiopharmaceutical, in patients with previously treated locally advanced or metastatic solid tumors: Phase 1b Nectinium-2 study
- Creators
- Timothy A. Yap - The University of Texas MD Anderson Cancer CenterOmar Alhalabi - The University of Texas MD Anderson Cancer CenterYang Lu - The University of Texas MD Anderson Cancer CenterBrandon Robert ManciniHarshad R. KulkarniKristin Plichta - University of Iowa Hospitals and ClinicsSerguei A. CastanedaFrankis AlmaguelRandy Yeh - Icahn School of Medicine at Mount SinaiRyan Reddy - Hoag Memorial Hospital PresbyterianDavid Joseph Benjamin - Hoag Memorial Hospital PresbyterianAbhishek Tripathi - City Of Hope National Medical CenterPhillip H. Kuo - City Of Hope National Medical CenterJulius Huang - North Carolina School of Science and MathematicsJanet K. Horton - AVEO Oncology (United States)Matthew D. Galsky - Tisch Cancer Institute
- Resource Type
- Abstract
- Publication Details
- Journal of clinical oncology, Vol.44(7_suppl), TPS902
- DOI
- 10.1200/JCO.2026.44.7_suppl.TPS902
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Publisher
- LIPPINCOTT WILLIAMS & WILKINS
- Language
- English
- Date published
- 03/2026
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9985141985502771
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