Aktis Oncology has received FDA clearance for investigational new drug applications for both therapeutic ([225Ac]Ac-AKY-1189) and imaging ([64Cu]Cu-AKY-1189) versions of its novel Nectin-4 targeted radiopharmaceutical, marking a significant milestone in precision oncology. The clearance enables initiation of the NECTINIUM-2 Phase 1b clinical trial, representing the first Nectin-4 targeted radiopharmaceutical to advance to therapeutic clinical studies.
Trial Design and Patient Population
The NECTINIUM-2 trial is a multicenter, US-based Phase 1b study expected to enroll approximately 150 patients. The trial will begin with dose escalation in patients with locally advanced or metastatic urothelial carcinoma (mUC), followed by dedicated expansion cohorts in mUC, triple negative breast cancer (TNBC), and other Nectin-4 expressing tumors, including lung, colorectal, and cervical cancers. Patients will receive up to six doses of [225Ac]Ac-AKY-1189.
"Radiopharmaceutical therapy targeting Nectin-4 is a highly attractive strategy, enabling the targeted delivery of radiation directly to tumor cells," said Matthew Galsky, M.D., co-director of the Center of Excellence for Bladder Cancer at The Tisch Cancer Institute at Mount Sinai Hospital in New York. "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."
Promising Preclinical and Early Clinical Data
AKY-1189 has demonstrated substantial tumor uptake across several solid tumor types in early clinical evaluation. Data presented in an oral plenary session at the 2024 EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics showed promising biodistribution profiles with significant tumor uptake in patients with mUC, metastatic breast cancer, non-small cell lung cancer carcinoma, colorectal cancer, and cervical cancer. Importantly, the radiopharmaceutical showed limited exposure to normal tissue, suggesting potential for a wide therapeutic window.
These findings marked the first report of a Nectin-4 targeted radiopharmaceutical candidate to demonstrate significant tumor uptake in patients, supporting progression into therapeutic clinical studies.
Targeting Nectin-4 for Precision Oncology
Nectin-4 is a cell-surface protein highly expressed in several solid tumors with limited expression in normal tissues, making it an attractive target for precision oncology therapies. AKY-1189 represents a potentially first-in-class approach using Aktis Oncology's proprietary miniprotein radioconjugate platform.
"Advancing the first product candidate from our proprietary miniprotein radioconjugate platform into Phase 1b clinical development in the U.S. is an important milestone for Aktis," said Akos Czibere, MD, PhD, Chief Medical Officer of Aktis Oncology. "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."
Platform Technology Advantages
Aktis' miniprotein radioconjugate platform is designed to generate tumor targeting agents with properties ideal for alpha radiopharmaceuticals. The platform is engineered to maximize tumor killing through high penetration followed by internalization and retention in cancer cells, while quickly clearing from normal organs and tissues to maximize anticancer activity while minimizing treatment side effects. The platform is isotope-agnostic and enables clinicians to visualize and verify target engagement with imaging isotopes prior to exposure to therapeutic radioisotopes.
