FDA Clears IND for Novel Nectin-4 Targeted Radiopharmaceutical Across Cancers

US FDA

• The FDA cleared investigational new drug (IND) applications for Aktis Oncology's [²²⁵Ac]Ac-AKY-1189 and [⁶⁴Cu]Cu-AKY-1189.
• This clearance enables the initiation of the NECTINIUM-2 phase 1b trial evaluating [²²⁵Ac]Ac-AKY-1189 in Nectin-4–expressing tumors.
• AKY-1189 is a novel Nectin-4–targeted radiopharmaceutical.

The FDA has granted clearance to the IND applications for both the therapeutic ([²²⁵Ac]Ac-AKY-1189) and imaging ([⁶⁴Cu]Cu-AKY-1189) versions of its novel Nectin-4–targeted radiopharmaceutical, AKY-1189. This clearance allows for the initiation of the NECTINIUM-2 phase 1b trial.¹

This multicenter, US-based study aims to evaluate the safety and preliminary efficacy of [²²⁵Ac]Ac-AKY-1189 in patients with locally advanced or metastatic urothelial carcinoma (mUC) during the dose-escalation phase. The trial will also expand to include specific cohorts of patients with mUC, triple negative breast cancer (TNBC), and other Nectin-4–expressing tumors, such as lung, colorectal, and cervical cancers.

Approximately 150 patients are expected to be enrolled and may receive up to 6 doses of the therapeutic radiopharmaceutical.

A close-up of a microscope lens capturing a vibrant blue cancer cell, symbolizing the groundbreaking findings: © catalin - stock.adobe.com

"Radiopharmaceutical therapy targeting Nectin-4 is a highly attractive strategy, enabling the targeted delivery of radiation directly to tumor cells. Building on the success of Nectin-4–directed antibody-drug conjugates, this approach combines imaging with therapeutic innovation to potentially personalize treatment for advanced urothelial cancer and other solid tumors. The NECTINIUM-2 trial, evaluating the safety and efficacy of the Nectin-4 radiopharmaceutical, [²²⁵Ac]Ac-AKY-1189, is a key step forward in advancing this concept," said Matthew Galsky, MD, co-director of the Center of Excellence for Bladder Cancer at The Tisch Cancer Institute at Mount Sinai Hospital in New York, in a press release.

About AKY-1189

This development introduces a potentially first-in-class targeted radiopharmaceutical approach for multiple solid tumors that are often challenging to treat. Nectin-4, a cell-surface protein highly expressed in these cancers with limited presence in normal tissues, presents an attractive target for precision oncology.

AKY-1189 is a novel Nectin-4–targeted radiopharmaceutical product candidate developed by Aktis Oncology. Preclinical and early clinical data presented at the 2024 EORTC-NCI-AACR Symposium demonstrated substantial tumor uptake of AKY-1189 across various Nectin-4–expressing solid tumor types, including mUC, metastatic breast cancer, non–small cell lung cancer, colorectal cancer, and cervical cancer, with limited exposure to normal tissue. This promising biodistribution profile suggests a potentially wide therapeutic window.

"Advancing the first product candidate from our proprietary miniprotein radioconjugate platform into phase 1b clinical development in the US is an important milestone for Aktis," said Akos Czibere, MD, PhD, chief medical officer of Aktis Oncology, in the press release. "Data presented to date demonstrates AKY-1189's substantial tumor uptake in patients with various Nectin-4–expressing tumor types with limited exposure to normal tissue, suggesting potential for a wide therapeutic window in addressing high unmet need patient populations."

REFERENCE:

1. Aktis Oncology initiates phase 1B clinical trial of its nectin-4-targeting radiopharmaceutical product candidate, AKY-1189, across multiple tumor types. News release. Aktis Oncology, Inc. May 28, 2025. Accessed May 28, 2025. https://tinyurl.com/2vy74dfv