Actinium unveils first-in-human ATNM 400 data in prostate cancer at EANM 2026

Actinium Pharmaceuticals, Inc. , a pioneer in differentiated targeted radiotherapies with the potential to transform cancer treatment, today announced encouraging initial clinical results from the first‑in‑human Phase 1 study of ATNM‑400 in metastatic castration‑resistant prostate cancer (mCRPC). The findings, presented in an oral presentation on October 19 at the 39th Annual Congress of the European Association of Nuclear Medicine (EANM) in Vienna, Austria, showed a favorable initial safety profile at the first dose level and tumor uptake and retention with the HER3‑targeted imaging agent. Dose escalation has advanced to 1.5 µCi/kg and is ongoing.

ATNM‑400 is a first‑in‑class, HER3‑targeted alpha radiotherapy that conjugates the monoclonal antibody barecetamab with Actinium‑225 (²²⁵Ac). HER3 is implicated in tumor progression and resistance to androgen receptor pathway inhibitors (ARPIs), providing a biology‑driven rationale for treatment beyond PSMA. ATNM‑400 combines the antigen specificity of a monoclonal antibody with the potent, high‑energy alpha‑particle radiation of ²²⁵Ac. The study employs a theranostic approach, using Zirconium‑89 (⁸⁹Zr)‑labeled barecetamab PET imaging to visualize tumor uptake and retention and characterize biodistribution and dosimetry to inform ATNM‑400 development.

Sandesh Seth, Actinium’s Chairman and CEO, said, “These first‑in‑human results mark an important milestone for a differentiated radiotherapy with the potential to expand treatment across the broad mCRPC population. HER3’s role in tumor survival and treatment resistance provides a compelling opportunity to address disease that remains underserved by existing approaches. Despite the progress of PSMA‑directed therapies, patients with PSMA‑low or PSMA‑negative disease and those who do not respond to or progress following these treatments need additional options. ATNM‑400 is designed to meet that need through a distinct target and potent alpha‑radiation payload. The initial tumor uptake and tolerability findings support continued clinical development in prostate cancer and our broader vision for ATNM‑400 as a pan‑cancer radiotherapy.”

Highlights from the EANM 2026 Oral Presentation

• Preclinical findings support broad potential beyond PSMA. ATNM‑400 demonstrated antitumor activity across PSMA‑high, PSMA‑low and PSMA‑negative prostate cancer models, including a model with low HER3 expression, supporting its potential to address patients underserved by PSMA‑directed therapies.
• HER3‑directed imaging demonstrated tumor uptake and retention. Serial imaging demonstrated lesion uptake retained through Day 7, supporting the use of ATNM‑400 to deliver high‑energy alpha‑particle radiation to tumors, with sustained retention aligned with the 10-day half‑life of ²²⁵Ac.
• First dose level cleared in three patients with previously treated mCRPC. Patients received ATNM‑400 at 1.0 µCi/kg. All had received prior ARPI therapy, two had received chemotherapy, and one had also received ¹⁷⁷Lu‑PSMA therapy. At the time of the presentation, all three had received at least two cycles of ATNM‑400, including two patients who had received three cycles.
• Encouraging initial safety findings supported continued dose escalation. No dose‑limiting toxicities, xerostomia (dry mouth), or Grade 3/4 hematologic adverse events were observed during the dose‑limiting toxicity window or subsequent follow‑up reported in the presentation. No elevations in liver enzymes (ALT/AST) or creatinine, injection‑site reactions, or infusion‑related reactions were observed.
• Study advanced to the second dose level. Following clearance of the 1.0 µCi/kg cohort, dose escalation proceeded to 1.5 µCi/kg. The study is designed to assess safety and tolerability and establish a recommended Phase 2 dose.

Professor Joe Cardaci of GenesisCare Murdoch, a study investigator and presenting author, commented, “Patients whose prostate cancer progresses after established therapies need additional treatment options. In this initial cohort, we observed HER3‑positive tumor uptake with the imaging agent and encouraging tolerability with repeated ATNM‑400 dosing, including in a patient previously treated with ¹⁷⁷Lu‑PSMA. The absence of dose‑limiting toxicities, xerostomia and Grade 3/4 hematologic adverse events is encouraging at this early stage. These findings support continued dose escalation and evaluation in additional patients.”

Steffen Heeger, MD, MSc, Actinium’s Chief Medical Officer, said, “HER3 is involved in tumor survival signaling and treatment resistance across multiple solid tumors, making it a compelling target for antibody‑directed alpha radiotherapy. In prostate cancer, its association with ARPI resistance provides a strong rationale for ATNM‑400, both as a monotherapy and in combination with established treatments. Preclinical activity across PSMA‑high, PSMA‑low and PSMA‑negative prostate cancer models, including a model with low HER3 expression, underscores the opportunity to reach patients underserved by PSMA‑directed therapies. Together with sustained tumor control after enzalutamide failure and durable activity in combination with enzalutamide, these findings support a broad mCRPC development strategy spanning monotherapy and ARPI combinations. We believe the combination of HER3 biology, sustained antibody localization and potent alpha radiation also supports investigation of ATNM‑400’s pan‑cancer potential, building on our preclinical findings in lung and breast cancer.”

 

About the ATNM‑400 Phase 1 Study
The ongoing first‑in‑human study uses a 3+3 dose‑escalation design followed by dose expansion in patients with progressive mCRPC who have received at least one ARPI and at least one taxane regimen, unless chemotherapy is unsuitable or declined. Prior ¹⁷⁷Lu‑PSMA treatment is permitted. Patients undergo HER3‑targeted PET imaging with [⁸⁹Zr]Zr‑barecetamab‑DFO before treatment with ATNM‑400, administered intravenously every six weeks for up to four cycles. Planned dose levels are 1.0, 1.5, 2.25 and 3.0 µCi/kg. The study evaluates safety, dosimetry and pharmacokinetics, with dose expansion intended to establish the recommended Phase 2 dose and further assess tolerability and antitumor activity, including PSA responses, objective response rate, radiographic progression‑free survival and overall survival.

About ATNM‑400 and HER3
ATNM‑400 is an investigational antibody radioconjugate that pairs the HER3‑targeting monoclonal antibody barecetamab with the alpha‑emitting isotope Actinium‑225. Its antibody‑based design combines antigen‑specific targeting with the potential for sustained tumor localization, supporting prolonged delivery of high‑energy alpha radiation. Tumor uptake and retention observed through Day 7 with the ⁸⁹Zr‑labeled imaging counterpart support this development rationale alongside the approximately 10‑day half‑life of ²²⁵Ac. The theranostic approach enables noninvasive visualization of antibody distribution to inform therapeutic development.

ATNM‑400 is differentiated from PSMA‑targeted radiotherapies by its focus on HER3, an antigen implicated in tumor survival and treatment resistance. ATNM‑400 combines HER3 targeting with an Actinium‑225 antibody radioconjugate, offering a distinct biological approach with the potential to expand radiotherapy across the broad mCRPC population, including patients with PSMA‑low or PSMA‑negative disease and those who do not respond to or progress following PSMA‑directed treatment. Its HER3‑directed mechanism also supports investigation beyond prostate cancer in other HER3‑expressing solid tumors.

HER3, also known as ERBB3, is a member of the epidermal growth factor receptor family involved in signaling pathways that support tumor growth, survival and resistance to treatment. HER3‑directed antibody‑drug conjugates in clinical development include BioNTech and MediLink’s BNT326/YL202, Bristol Myers Squibb and SystImmune’s EGFR × HER3 bispecific ADC izalontamab brengitecan (iza‑bren), and Daiichi Sankyo and Merck’s patritumab deruxtecan (HER3‑DXd). These programs underscore the clinical development interest in HER3 as an oncology target. ATNM‑400 applies a distinct payload strategy, using alpha radiation in place of a conventional cytotoxic drug. Its preclinical activity in prostate, non‑small cell lung and breast cancer models supports investigation as a potential pan‑cancer radiotherapy, as a monotherapy and in rational combinations.