Investigators shared fresh findings from early-phase clinical studies of 177Lu-NeoB, a targeted radioligand therapy designed for tumours expressing gastrin-releasing peptide receptors (GRPR). The therapy combines a high-affinity GRPR antagonist (NeoB) with the radionuclide lutetium-177, aiming to deliver beta-radiation selectively to cancer cells while sparing healthy tissue.

Key centres participating in the studies screened patients with advanced or metastatic solid tumours including prostate cancer, breast cancer, glioblastoma, and gastrointestinal stromal tumour selected on the basis of GRPR expression via diagnostic imaging (such as PET or PET/CT). Eligible patients received 177Lu-NeoB under a dose-escalation schedule in a Phase I/IIa trial to assess safety, tolerability, dosimetry, and preliminary anti-tumour activity.

Some patients also received combination therapies: for example, in certain cohorts of estrogen receptor-positive (ER+), HER2-negative, GRPR-positive advanced breast cancer, the radioligand was paired with standard hormonal treatments such as fulvestrant, or with other agents aiming to delay progression after prior lines of therapy. In these cohorts responses included measurable tumour shrinkage in a subset of patients, disease stabilization in others, and overall tolerable safety profile without severe off-tumour effects in major organs such as kidneys or heart.

Dosimetry evaluations suggested that radiation exposure to non-target organs remained within acceptable limits in most patients, though higher doses approached safety thresholds in some kidney tissue measurements, necessitating careful patient monitoring. Adverse events of moderate severity included mild to moderate hematologic changes (such as transient drops in blood cell counts), fatigue, and gastrointestinal symptoms, but serious toxicity was rare.

Why this matters

Radioligand therapies represent a growing frontier in oncology, offering precise targeting of tumour cells using molecular markers. When agents like 177Lu-NeoB can be matched to tumours that express GRPR, this opens possibilities for treating cancers that have been hard to control with conventional systemic therapies.

For patients with breast cancer or prostate cancer that overexpress GRPR, this approach could add another line of therapy, particularly in advanced or metastatic settings. The combination trials with endocrine therapy or other agents are especially intriguing, because they suggest that targeting GRPR might enhance or synergize with existing treatments.

Also important is dosimetry data: ensuring that the therapeutic window (high tumour dose, low normal organ exposure) is maintained is critical for radiopharmaceuticals. The early results suggest that although there are risks, they may be manageable with proper selection and monitoring.

Points to watch

Because these are early-phase trials, longer follow-up will be needed to see how durable responses are, whether tumour shrinkage translates into improved overall survival or quality of life, and how the therapy behaves in larger patient populations.

Patient selection will be crucial. The level of GRPR expression seems to correlate with uptake of the therapy; identifying the right threshold and imaging technique matters. Also, combining radioligand therapy with other agents can raise complexity: interactions, toxicity, and timing of therapy need optimisation.

Regulatory pathways for radioligands are evolving, especially for first-in-class or novel combinations. Manufacturers will need to document both efficacy and safety carefully, including in less typical populations.

Finally, cost, availability, and infrastructure (especially imaging capacity for GRPR screening, facilities for handling radiotherapeutics) will influence whether such therapy can scale beyond specialised centres.