ATNM-400 Shows Promising Antitumor Activity in Preclinical Cancer Models

Actinium Pharmaceuticals, Inc. has announced new preclinical results showcasing the potential of ATNM-400, a first-in-class Actinium-225 (²²⁵Ac) antibody radioconjugate targeting HER3. These findings, presented at the 39th Annual Congress of the European Association of Nuclear Medicine (EANM), highlight ATNM-400's antitumor activity across non-small cell lung cancer (NSCLC), colorectal cancer, and ovarian cancer models.

Non-Small Cell Lung Cancer

ATNM-400 demonstrated significant activity in various NSCLC models driven by EGFR, KRAS, and ALK mutations. In the KRAS G12C-mutant NCI-H358 model, ATNM-400 monotherapy achieved an 81% tumor growth inhibition (TGI), surpassing results from other treatments. Combinations with adagrasib yielded a TGI of 105%. In the ALK-rearranged NCI-H3122 model, ATNM-400 plus crizotinib produced a 97% TGI. The EGFR-mutant NCI-H1975 model saw ATNM-400 combined with pemetrexed and cisplatin achieving an 86% TGI.

Colorectal Cancer

In colorectal cancer models, the combination of ATNM-400 with oxaliplatin and bevacizumab resulted in a TGI of 72% in the HCT15 model, achieving a significant improvement over standard therapy alone. This enhancement in tumor control supports the potential of ATNM-400 in enhancing therapeutic responses, especially in tumors with moderate HER3 expression.

Ovarian Cancer

ATNM-400's efficacy was also evident in ovarian cancer, with monotherapy achieving a remarkable 93% TGI in the OVCAR-5 model. Importantly, ATNM-400 retained activity even after bevacizumab failure, achieving a 50% TGI in such treatment-resistant scenarios. Furthermore, in an immunocompetent model of disseminated ovarian cancer, ATNM-400-containing regimens demonstrated prolonged survival compared to controls.

Tolerability and Future Development

Overall, studies reported favorable tolerability in animal models, with minimal adverse changes in blood and organ markers. Actinium's strategies extend beyond traditional oncology treatments, aiming for ATNM-400 to function as a backbone therapy in solid tumor indications.

The promising results across various cancer models indicate the potential of ATNM-400 as a versatile treatment option that warrants further clinical exploration. Actinium Pharmaceuticals continues to advance its development, positioning ATNM-400 as a focal point in targeted cancer therapies.