Actinium Pharmaceuticals Reports Positive Initial Results from ATNM-400 Phase 1 Study in mCRPC

Actinium Pharmaceuticals, Inc. recently presented initial clinical findings from its first-in-human Phase 1 study of ATNM-400, an investigational radiotherapeutic for metastatic castration-resistant prostate cancer (mCRPC). These results were shared during an oral presentation at the 39th Annual Congress of the European Association of Nuclear Medicine (EANM) on October 19 in Vienna, Austria.

The Phase 1 study focuses on establishing the safety and tolerability of ATNM-400, a HER3-targeted alpha radiotherapy that pairs the monoclonal antibody barecetamab with Actinium-225 (²²⁵Ac). Noteworthy findings indicate that the first cohort of three patients tolerated the initial dose level of 1.0 µCi/kg without experiencing dose-limiting toxicities, xerostomia, or Grade 3/4 hematologic adverse events.

Key data from the study reveal that HER3-targeted PET imaging demonstrated tumor uptake and retention. Serial imaging assessments showed that this uptake persisted through Day 7, aligning with the 10-day half-life of ²²⁵Ac. Following clearance of the first dose level, the trial has advanced to the second dose of 1.5 µCi/kg.

ATNM-400 aims to address a patient population underserved by PSMA-directed therapies, as HER3 is implicated in tumor progression and resistance to androgen receptor pathway inhibitors (ARPIs). The rationale for ATNM-400 is underscored by preclinical evidence of its antitumor activity across various prostate cancer models, including those with low HER3 expression.

Sandesh Seth, Actinium's Chairman and CEO, remarked on the significance of these results, highlighting the need for new treatment options for patients with PSMA-low or PSMA-negative disease, referencing ongoing challenges that current therapies do not address.

Professor Joe Cardaci, an investigator in the study, noted the encouraging tolerability and initial observations of HER3-positive tumor uptake, which provide a positive outlook for the continued clinical evaluation of ATNM-400 in upcoming patient cohorts.

The ongoing first-in-human study employs a 3+3 dose-escalation design with planned dose levels of 1.0, 1.5, 2.25, and 3.0 µCi/kg administered intravenously every six weeks. The trial assesses various metrics, including safety, dosimetry, pharmacokinetics, and potential antitumor activity.

Through its innovative approach, ATNM-400 represents an important advancement in the field of targeted radiotherapy, with implications for broader cancer treatment beyond prostate cancer. The continued evaluation of this novel therapy is expected to provide further insights into its efficacy and safety profile.