FDA grants fast track designation to nectin-4 radioconjugate for urothelial carcinoma

The FDA has granted fast track designation to AKY-1189, a nectin-4 miniprotein radioconjugate, for adult patients with locally advanced or metastatic urothelial carcinoma (la/mUC) whose disease progressed on or after prior systemic therapies, Aktis Oncology announced.¹

According to the company, AKY-1189 is “designed to deliver actinium-225 (²²⁵Ac), a highly potent alpha-emitting radioisotope, to Nectin-4 expressing tumors.” The agent was generated using Aktis’ miniprotein radioconjugate platform.

Fast track designation is granted to novel agents that are intended to treat or prevent serious or life-threatening conditions and have the potential to address an unmet medical need. With this designation, the development process for AKY-1189 can benefit from more frequent engagement with the FDA and eligibility for accelerated approval and priority review.

“Patients with locally advanced or metastatic urothelial cancer who progress on systemic therapies, such as PADCEV, have limited treatment options,” said Akos Czibere, MD, PhD, Chief Medical Officer of Aktis Oncology, in the news release.¹ “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.”

AKY-1189 is currently under investigation in the phase 1b NECTINIUM-2 trial (NCT07020117) to assess its safety and efficacy in patients with solid tumors, including la/mUC, breast cancer, non-small cell lung cancer, colorectal cancer, cervical cancer, and head and neck cancer.² The study is being conducted in a 2-part dose escalation and dose expansion design.

In part 1, patients will receive ascending doses of AKY-1189 for up to 6 cycles. The goals are to determine a maximum tolerated dose and the recommended phase 2 dose for expansion. Part 2 of the study will further assess the efficacy of AKY-1189 at the recommended phase 2 dose across 3 different cohorts of patients.

In total, the open-label, multicenter trial plans to enroll up to 150 patients through clinical trial sites across the US. Patients are eligible for enrollment if they have histologic or cytologic confirmation of locally advanced or metastatic disease, radiologic confirmation on CT or at least 1 measurable lesion per RECIST v1.1, and documented disease progression on a prior line of therapy for metastatic disease. Participants must also have an ECOG performance status of 0 or 1 and adequate end-organ function.

The primary end points for part 1 of the study are the number of patients with dose-limiting toxicities and the occurrence of adverse events. The primary objective for part 2 is the objective response rate. Secondary objectives in both part 1 and part 2 of the study include the duration of response and progression-free survival, as assessed for up to 5 years following the first administration of treatment.

According to Aktis, preliminary results from part 1 of the study are expected in the first quarter of 2027. Final completion of the study is anticipated in June 2032.

REFERENCES

1. Aktis Oncology receives U.S. FDA fast track designation for AKY-1189, a nectin-4 miniprotein radioconjugate. News release. Aktis Oncology Inc. February 24, 2026. Accessed February 24, 2026. https://www.globenewswire.com/news-release/2026/02/24/3243465/0/en/Aktis-Oncology-Receives-U-S-FDA-Fast-Track-Designation-for-AKY-1189-a-Nectin-4-Miniprotein-Radioconjugate.html

2. A study of [225Ac]Ac-AKY-1189 in patients with solid tumors. ClinicalTrials.gov. Last updated November 26, 2025. Accessed February 24, 2026. https://clinicaltrials.gov/study/NCT07020117