Actinium Pharmaceuticals to share new radiotherapy research on ATNM-400 across solid tumors at AACR-NCI-EORTC 2025

Actinium Pharmaceuticals, Inc.), a leader in the development of differentiated targeted radiotherapies  announced that the first-ever preclinical data from its ATNM-400 program in non-small cell lung cancer (NSCLC) has been accepted for presentation at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics being held October 22 – 26, 2025, at the Hynes Convention Center in Boston, Massachusetts. ATNM-400 is a highly innovative, first-in-class, Actinium-225 (Ac-225) antibody radioconjugate with preclinical data in both prostate cancer and NSCLC. Together, these two indications represent more than 500,000 new cases annually in the U.S. alone.

ATNM-400 in NSCLC: Addressing Resistance to EGFR TKIs

NSCLC accounts for approximately 85% of lung cancer cases and remains the leading cause of cancer mortality worldwide. While EGFR tyrosine kinase inhibitors (TKIs) such as osimertinib (TAGRISSO^®, AstraZeneca) have transformed outcomes for patients with EGFR-mutant NSCLC, virtually all patients develop resistance within 2 to 3 years, leading to disease progression and a lack of effective therapeutic options.

Preclinical data to be presented at AACR-NCI-EORTC conference demonstrate that ATNM-400 exerts potent anti-tumor activity in EGFR-mutant NSCLC models and is capable of overcoming resistance to osimertinib and is furthermore synergistic in combination osimertinib. This represents a potential breakthrough for patients with relapsed or refractory EGFR-mutant NSCLC, one of the most urgent areas of unmet need in oncology.

In the multicenter, single-arm Phase 2 trial titled “osimertinib plus consolidative radiotherapy for advanced EGFR-mutant non-small cell lung cancer,” Sampath et al. (AstraZeneca & UT Southwestern Harold C. Simmons Comprehensive Cancer Center) reported a median progression-free survival (PFS) of 32.3 months. This reflects a notable 12.3-month improvement over the 20.0-month median PFS observed with osimertinib monotherapy, as reported by Watanabe et al. in a real-world clinical setting.

ATNM-400 Presentation Information

Title: ATNM-400, a first-in-class Actinium-225 antibody radioconjugate, demonstrates potent anti-tumor activity and overcomes osimertinib resistance in lung cancer models

Session: Poster Session C

Session Date and Time: Saturday, October 25, 2025, 12:30 – 4:00 PM E.T.

The ATNM-400 abstract will be available for viewing online on October 22, 2025 at 12:00 PM E.T. through a freely available supplement in the AACR journal Molecular Cancer Therapeutics.

Expanding Beyond Prostate Cancer: Multi-Indication Potential

ATNM-400 was initially developed in prostate cancer, where it has demonstrated unique differentiation from PSMA-targeting radiotherapies such as 177Lu-PSMA-617 (active ingredient of Pluvicto®, Novartis). Unlike PSMA-directed agents, ATNM-400 targets a distinct receptor implicated in tumor progression and treatment resistance, remaining active in PSMA-low or PSMA-resistant disease – a major limitation of current radiopharmaceuticals. The target antigen of ATNM-400 is overexpressed following ARPI therapy and is associated with a shorter time to castration resistance. This positions ATNM-400 as a differentiated treatment option in the post-ARPI setting, where it has been shown to overcome enzalutamide resistance and enhance the efficacy of ARPI combinations. In preclinical models, synergy with enzalutamide resulted in robust, durable tumor control and significantly improved overall survival.

In both prostate and lung cancer, ATNM-400 leverages the potent, high-linear-energy-transfer emissions of Ac-225 to induce irreparable double-strand DNA breaks, a mechanism expected to overcome conventional resistance pathways and deliver durable tumor control.

Sandesh Seth, Actinium’s Chairman and CEO, said, “We are excited to share the first data demonstrating that ATNM-400 can overcome resistance to osimertinib in NSCLC, one of the most challenging settings in oncology today. ATNM-400 has demonstrated compelling multi-indication potential in both mCRPC and NSCLC, showing greater efficacy as a monotherapy than standard-of-care agents including ¹⁷⁷Lu-PSMA-617, enzalutamide, and osimertinib. In combination with enzalutamide, ATNM-400 delivered superior anti-tumor activity compared to enzalutamide alone, including complete tumor regressions in 40% of prostate cancer-bearing animals and significantly extended their survival. Notably, ATNM-400 also overcame resistance to standard of care therapies in relapse settings, highlighting its promise in treatment-refractory disease.” Mr. Seth added, “This data in NSCLC expands the potential of ATNM-400 far beyond prostate cancer into another major cancer indication with significant unmet patient need. By leveraging the Actinium-225 alpha-emitter payload and targeting a receptor implicated in multiple tumor types, ATNM-400 has the potential to become a transformative therapy across two of the largest and most difficult-to-treat solid tumors.”