Radiopharmaceuticals continue to attract growing attention across oncology. By combining the targeting precision of antibodies or small molecules with the destructive power of radioactive isotopes, these agents aim to deliver therapy directly into cancer cells while sparing surrounding tissue. On 28 May 2025, two companies — Aktis Oncology and Archeus Technologies — announced key steps forward in the clinic.

AKY-1189 in Nectin-4 Positive Tumors

Aktis Oncology confirmed that its lead candidate, AKY-1189, has officially entered a Phase 1b trial named NECTINIUM-2. This study will recruit around 150 patients with solid tumors expressing Nectin-4, a protein overexpressed in several difficult-to-treat cancers including urothelial carcinoma, triple-negative breast cancer, and certain head and neck cancers.

The program features both a therapeutic version, which uses actinium-225, and a diagnostic version labeled with copper-64 for imaging. The dual approach allows researchers to measure how well the compound binds and concentrates in tumors before deciding whether a patient is suitable for therapeutic dosing.

Early human data from the initial Phase 1a portion, along with supportive preclinical studies, showed strong tumor uptake and minimal accumulation in non-target tissues such as the kidneys and liver. This favorable biodistribution is critical for radiopharmaceuticals, since off-target radiation exposure often limits their safety profile. Patients in NECTINIUM-2 will be eligible to receive up to six cycles of therapy, with interim results expected in late 2026.

ART-101 and a New Path in Prostate Cancer

On the same day, Archeus Technologies announced that it will be advancing ART-101 into human testing through a collaboration with the Wisconsin Alumni Research Foundation. ART-101 targets PSMA (prostate-specific membrane antigen), a well-established biomarker in prostate cancer.

Preclinical studies suggest ART-101 may deliver a higher level of radiation to tumor cells compared with the currently approved PSMA-targeted radiopharmaceuticals. Investigators also reported longer tumor retention and lower accumulation in non-cancerous tissues such as the salivary glands, which are commonly affected in PSMA radiotherapy. If these findings translate to patients, ART-101 could represent a significant improvement in both safety and efficacy for men with advanced prostate cancer.

The company expects to begin a Phase 1 trial later this year, focusing first on safety, dosimetry, and imaging endpoints before moving to larger efficacy cohorts.

Broader Implications for Oncology Research

These two announcements highlight the broader momentum in radiopharmaceuticals, a field that has seen a surge in investment and clinical activity over the past three years. Several trends are becoming increasingly clear:

• Theranostic pairing — Using both a diagnostic and a therapeutic agent based on the same target allows more precise patient selection. It helps ensure that the radioactive therapy will actually reach tumors at therapeutic levels before exposing patients to radiation.
• Improved isotope handling — Advances in isotope chemistry and supply chain logistics are making it easier to design molecules with better tumor penetration, higher stability, and faster clearance from healthy tissues.
• Expanding target scope — While PSMA has dominated the field in prostate cancer, new targets like Nectin-4 demonstrate how radiopharmaceuticals are moving into breast, bladder, and head and neck cancers. This diversification could expand the impact of this therapeutic approach far beyond its current reach.
• Regulatory support — Agencies such as the FDA are providing clearer guidance on how to evaluate radiopharmaceutical safety and efficacy. The use of combined imaging and therapeutic protocols is increasingly recognized as a strength rather than a complication in trial design.

Looking Ahead

Over the next year, the oncology community will be watching closely for safety readouts from both AKY-1189 and ART-101. A key question will be whether the early promise seen in preclinical and first-in-human studies holds up when scaled across larger and more diverse patient groups.

For patients with advanced cancers that often resist conventional therapies, the appeal of a more targeted, radiation-based approach is clear. Success in these trials could pave the way for a new wave of theranostic medicines, capable of diagnosing, selecting, and treating patients all within the same clinical pathway.

As of today, the progress of AKY-1189 and ART-101 stands as another sign that radiopharmaceuticals are no longer a niche pursuit but a rapidly maturing field with the potential to change standards of care in oncology.