Weiss on How Nanoparticles are Enhancing Radiation Therapy in Lung Cancer
JNJ-1900 (NBTXR3), a novel radioenhancer, shows promises as an innovative approach to enhance local tumor control without escalating systemic toxicity across solid tumors, including lung cancer, according to preliminary findings from an ongoing phase 1 study (NCT03589339) presented at the 2025 European Lung Cancer Congress (ELCC).
In an interview with Targeted OncologyTM, Jared Weiss, MD, professor of medicine and section chief of thoracic and head and neck oncology at UNC Lineberger Comprehensive Cancer Center, explains the mechanism of action of JNJ-1900.
According to Weiss, hafnium nanoparticles are locally injected into tumors prior to hypofractionated radiation therapy to achieve 2 desirable clinical outcomes: enhanced local tumor ablation and the induction of a systemic immune response. The mechanism underlying the local tumor destruction is relatively well understood. Upon irradiation with photons, each hafnium nanoparticle absorbs a photon and subsequently releases approximately 9 electrons. Due to the limited penetration range of these electrons, this process results in a highly localized amplification of the radiation's cytotoxic effect, potentially enabling effective treatment even in previously irradiated areas.
The mechanism behind the observed systemic immune response, while exhibiting promising preclinical and clinical evidence, remains less definitively established, both with hypofractionated radiation alone and in combination with hafnium nanoparticles. However, data have demonstrated documented abscopal responses in untreated lesions, suggesting the potential for this systemic effect. While the term "abscopal effect" is often used with a degree of skepticism within the medical oncology and radiation oncology communities due to its infrequent real-world observation, the findings provide compelling evidence for its occurrence in this context.
JNJ-1900 is also being evaluated in the global, phase 3 NANORAY-312 trial (NCT04892173) in head and neck cancer and lung cancer, a phase 2 trial in unresectable stage 3 non–small cell lung cancer (NSCLC), the phase 1 MDA 2019-1001 study in locally advanced or borderline resectable pancreatic cancer, and the phase 1 MDA 2020-0123 study in NSCLC amenable to re-irradiation.
