Vienna, Austria, October 20, 2026
Actinium Pharmaceuticals has announced encouraging initial clinical findings for ATNM-400, an investigational HER3-targeted alpha radiotherapy being developed for patients with metastatic castration-resistant prostate cancer (mCRPC). The company presented results from its first-in-human Phase 1 study at the 39th Annual Congress of the European Association of Nuclear Medicine (EANM 2026) in Vienna, Austria. The findings highlighted an encouraging initial safety profile and evidence that HER3-targeted imaging can identify and track the investigational therapy’s tumor uptake and retention. The research represents an important step in exploring targeted radiotherapy approaches that could potentially extend treatment options beyond prostate-specific membrane antigen (PSMA)-directed therapies. ATNM-400 remains investigational, and further clinical evaluation is required to establish its safety, efficacy and appropriate dosing.
ATNM-400 Targets HER3 Beyond Conventional PSMA Approaches
ATNM-400 is a first-in-class antibody radioconjugate designed to target human epidermal growth factor receptor 3 (HER3), a protein associated with tumor-cell survival, disease progression and treatment resistance. The investigational treatment combines the HER3-targeting monoclonal antibody barecetamab with actinium-225, an alpha-particle-emitting radioactive isotope. This design aims to direct radiation toward HER3-expressing tumor cells while using antibody specificity to support targeted delivery. The scientific rationale is particularly relevant to patients with mCRPC whose disease progresses despite androgen receptor pathway inhibitor (ARPI) treatment. Although PSMA-directed radiotherapies have expanded treatment options for prostate cancer, some patients have tumors with low or absent PSMA expression, while others experience disease progression after treatment. By focusing on a different biological target, ATNM-400 is being investigated as a potential alternative approach for a broader patient population, including those who may not benefit sufficiently from PSMA-directed strategies. Preclinical findings reported by the company have also indicated antitumor activity across prostate cancer models with different levels of PSMA expression. These results provide a scientific rationale for further investigating HER3-targeted radiotherapy, although laboratory findings cannot establish clinical benefit in patients.
Early Phase 1 Findings Show Tumor Uptake and Initial Tolerability
The initial clinical data came from three patients who completed the first dose level of 1.0 microcurie per kilogram (µCi/kg). All three patients had previously received ARPI treatment, while two had also received chemotherapy. One patient had previously received lutetium-177 PSMA-directed therapy. The study incorporated zirconium-89-labelled barecetamab PET imaging to assess the investigational antibody’s distribution, tumor uptake and retention. Serial imaging demonstrated tumor-lesion uptake retained through Day 7, supporting further investigation of the approach for delivering radiation to targeted tumors. The imaging strategy is intended to help researchers understand how the antibody distributes in the body and inform the development of the therapeutic actinium-225-labelled product. According to the company’s presentation, no dose-limiting toxicities, dry mouth (xerostomia), or Grade 3 or 4 hematologic adverse events were observed in the initial cohort during the reported assessment period and follow-up. These early observations are encouraging but are based on only three patients and should not be interpreted as definitive evidence of safety. Larger patient cohorts and longer follow-up will be necessary to characterize the treatment’s risk profile. Following completion of the initial dose level, the trial advanced to 1.5 µCi/kg, continuing the planned dose-escalation process.
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Continued Development Will Assess Safety and Antitumor Activity
The ongoing Phase 1 study uses a dose-escalation design followed by planned dose expansion in patients with progressive mCRPC who have received prior ARPI and taxane-based treatment, subject to the protocol’s eligibility criteria. ATNM-400 is administered intravenously every six weeks for up to four cycles. Researchers are assessing safety, tolerability, pharmacokinetics, dosimetry and preliminary antitumor activity. Planned assessments include prostate-specific antigen (PSA) responses, objective response rate, radiographic progression-free survival and overall survival. The study is intended to identify a recommended Phase 2 dose and provide additional evidence to guide subsequent development. For Actinium Pharmaceuticals, the findings support continued investigation of a differentiated radiopharmaceutical strategy that combines HER3 targeting with alpha radiation. The approach could eventually have relevance beyond prostate cancer, but its potential in other solid tumors remains under investigation. The EANM 2026 presentation marks an early milestone for ATNM-400. Future clinical results will be important in determining whether the imaging findings and initial tolerability observations translate into meaningful outcomes for patients with advanced prostate cancer.
Source: Actinium Pharmaceuticals press release
