What question did this study set out to answer?

The study aims to evaluate the safety and efficacy of [225 Ac]Ac-AKY-1189 in patients with advanced solid tumors.

March 4, 2026

225 AcAc-AKY-1189, a Nectin-4 targeted radiopharmaceutical, in patients with previously treated locally advanced or metastatic solid tumors: Phase 1b Nectinium-2 study.

TYT. A. YapThe University of Texas MD Anderson Cancer Center OAOmar AlhalabiThe University of Texas MD Anderson Cancer Center YLYang LüThe University of Texas MD Anderson Cancer Center

Key Points

The study aims to evaluate the safety and efficacy of [225 Ac]Ac-AKY-1189 in patients with advanced solid tumors.
Phase 1b, multi-center, open-label design with two parts: dose escalation and expansion.
Inclusion of patients aged ≥18 with measurable Nectin-4 positive solid tumors.
Dose escalation to determine maximum tolerated dose (MTD) in approximately 30 patients.
[225 Ac]Ac-AKY-1189 induced regression and stasis in preclinical models of urothelial carcinoma.
Patient recruitment has started in the United States, suggesting positive early outcomes.

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 AcAc-AKY-1189 is under development for the treatment of patients with locally advanced or metastatic solid tumors. 225 AcAc-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 AcAc-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 AcAc-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 CuCu-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 AcAc-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 AcAc-AKY-1189. Once RP2D is established, part 2 will evaluate the clinical activity of 225 AcAc-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 .

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