AKY-1189, Alpha-Emitting Radioisotope, Fast Tracked for Urothelial Cancer

The FDA has granted Fast Track Designation to AKY-1189 (actinium-225; ²²⁵Ac) a potent alpha-emitting radioisotope in the potential treatment of Nectin-4 expressing tumors in urothelial carcinoma.¹ It is estimated that about 90% of patients with urothelial cancer show positive expression of Nectin-04.

The agent is currently undergoing evaluation in an ongoing phase 1b, 2-part, multicenter open-label trial (NCT07020117) to evaluate safety and efficacy in patients with locally advanced or metastatic solid tumors and to establish the maximum tolerated dose (MTD) or maximum administered dose (MAD) and the recommended phase 2 dose. Findings were presented during the 2026 ASCO Genitourinary Cancers Symposium, February 26-28, 2026.²

“The granting of Fast Track designation affords us a unique opportunity to work closely with the FDA to potentially expedite the development and review process of AKY-1189 with the goal of addressing this unmet medical need by bringing a new therapeutic option to patients with locally advanced or metastatic urothelial cancer,” Akos Czibere, MD, PhD, chief medical officer of Aktis Oncology, said in a release.¹

Trial Details

Part 1 is the dose escalation portion of the study, which will investigate ascending doses of [225Ac]Ac-AKY-1189 (up to 6 cycles) in patients with locally advanced or metastatic solid tumors. The aim of part 1 is to determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and the recommended phase 2 dose.

Part 2 will be the dose expansion portion of the study and will enroll locally advanced or metastatic solid tumor patients who are identified as Nectin-4 positive by [64Cu] Cu-AKY-1189. Part 2 aims to further assess the efficacy of [225Ac]Ac-AKY-1189 at the RP2D in 3 different cohorts of patients.

The primary end points are safety and tolerability and the secondary end points are pharmacokinetics and preliminary antitumor activity. Eligible patients had histologically confirmed locally advanced or metastatic solid tumors, ECOG performance status of 0 to 1, and adequate end-organ function.

Nectin-4 is a clinically validated target in metastatic urothelial carcinoma and is overexpressed across multiple additional solid tumors, supporting broad therapeutic potential.

Fast track designation is an FDA process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. The purpose is to bring important new drugs to patients earlier. A drug that receives fast track designation may be eligible for more frequent interactions and communications with the FDA and the ability to submit a Biologics License Application on a rolling basis.

REFERENCES

1. Aktis Oncology Receives U.S. FDA Fast Track Designation for AKY-1189, a Nectin-4 Miniprotein Radioconjugate. News release. February 24, 2026. Accessed March 4, 2026. https://finance.yahoo.com/news/aktis-oncology-receives-u-fda-130000308.html

2. Yap TA, Alhalabi O, Lu Yang, et al. [225Ac]Ac-AKY-1189, a Nectin-4 targeted radiopharmaceutical, in patients with previously treated locally advanced metastatic solid tumors: Phase 1b Nectinium-2 study. J Clin Oncol. 2026;44(suppl 7):TPS902. doi:10.1200/JCO.2026.44.7_suppl.TPS902.