Phase 1 Study of ATNM-400 for mCRPC Set for ESMO 2026

Actinium Pharmaceuticals, Inc. has announced that its first-in-human Phase 1 study evaluating ATNM-400, a HER3-targeted, non-PSMA radiotherapy for metastatic castration-resistant prostate cancer (mCRPC), will be featured at the European Society for Medical Oncology (ESMO) Congress 2026, scheduled for October 23–27, 2026, in Madrid, Spain.

ATNM-400 is an investigational monoclonal antibody radioconjugate designed to target HER3, an antigen associated with tumor survival and treatment resistance. This therapy aims to reach a broad mCRPC patient population, including those with PSMA-positive, PSMA-low, or PSMA-negative tumors, as well as patients who have either not received PSMA-directed therapies or those who progressed following such treatments. The study incorporates Zirconium-89-labeled ATNM-400 imaging to guide patient selection and dosing for the therapeutic Actinium-225-labeled ATNM-400.

"We are excited to take this first step in our pan-cancer strategy for ATNM-400 with its first-in-human Phase 1 study in prostate cancer," stated Sandesh Seth, Chairman and CEO of Actinium. Initial results presented at EANM indicated effective tumor retention of the HER3-targeted imaging and a favorable tolerability profile, which spurs optimism for ATNM-400’s ability to impact a wide mCRPC spectrum.

The Phase 1 study is a multicenter, open-label, dose-escalation trial enrolling patients previously treated with androgen receptor pathway inhibitors and taxane chemotherapy. While previous treatment with lutetium is allowed, it is not mandatory for enrollment. Patients demonstrating positive imaging with Zirconium-89-ATNM-400 will receive Actinium-225-ATNM-400 treatment every six weeks for a maximum of four cycles. The primary objective of the trial is to assess safety and tolerability and establish a recommended Phase 2 dose, alongside evaluations of dosimetry, pharmacokinetics, and antitumor activity.

"Our clinical strategy uses imaging to understand where ATNM-400 distributes, how much reaches tumors, and how long it is retained," said Steffen Heeger, MD, MSc, Actinium's Chief Medical Officer. HER3 signaling is believed to bolster prostate cancer cell growth and survival while contributing to therapy resistance. The rationale for evaluating HER3-targeted radiotherapy in mCRPC is strongly supported by its connection to disease progression and therapeutic efficacy.

The details of the ATNM-400 presentation at ESMO 2026 are as follows:
Abstract Title: First-in-human phase 1 study of ATNM-400, Actinium-225 antibody radioconjugate, in metastatic castration-resistant prostate cancer (mCRPC)
Abstract Number: 2386eTiP
Presentation Type: ePoster — Trial in Progress
Category: Metastatic prostate cancer
Presenter: Jeri Kim, MD, Houston, United States of America.