Data Shows Radioenhancer Produces Significant Antitumor Effects in Resistant Lung Cancer Models

Preclinical data in an anti-PD-1 resistant lung cancer model showed that adding NBTXR3 to a combination of radiotherapy, anti-PD-1, and anti-CTLA-4 produced significant antitumor effects against both primary and secondary tumors, improved the mouse survival rate from 0 to 50%, and induced long term antitumor memory. The data was published in the Journal of Nanobiotechnology.

The Nanobiotix preclinical program aims both to provide a deeper understanding of the NBTXR3 mechanism of action and to discover new pathways for the radioenhancer to potentially improve treatment outcomes for patients. Given preclinical and early clinical data suggesting a potential immune priming effect triggered by radiotherapy (RT)-activated NBTXR3 and the medical unmet need for patients with primary or secondary resistance to immune checkpoint inhibitors, Nanobiotix and The University of Texas MD Anderson Cancer Center are exploring several therapeutic combinations involving checkpoint inhibitors, radiotherapy, and NBTXR3.

“We believe that we have only scratched the surface of opportunity for NBTXR3 as a potentially-ideal combination agent with immune checkpoint inhibitors,” said Laurent Levy, co-founder and chairman of the executive board at Nanobiotix. “As the industry continues to advance development of these powerful immunotherapy agents, we feel there is an urgent need for novel combinations that can help improve efficacy for naïve patients and overcome resistance for non-responders. Our view is that the results presented in this new publication add to the growing body of data suggesting therapeutic potential for NBTXR3 in combination with immune checkpoint inhibitors, and we look forward to further investigation in the lab and in the clinic.”

Following previously reported positive preclinical data on the addition of NBTXR3 to a combination of radiotherapy and anti-PD-1 in anti-PD-1 sensitive and resistant lung cancer models, this evaluation investigated the addition of NBTXR3 to a combination of radiotherapy, anti-PD-1, and anti-CTLA-4 in an anti-PD-1 resistant model. Mice were inoculated with metastatic lung cancer cells in their right (primary tumor) and left (secondary tumor) legs. They were then treated with various combinations of anti-PD-1, anti-CTLA-4, NBTXR3, and radiotherapy in an effort to isolate the effect of adding NBTXR3, modifying the RT protocol, or both. Mice surviving after 178 days were rechallenged with tumor cells and monitored for tumor growth.

The evaluation showed that both modifications to RT protocol and the addition of NBTXR3 improved outcomes of combination therapy, and that the cohorts in which NBTXR3 was included in the regimen outperformed all others. Of note, the cohort treated with NBTXR3 and modified RT together showed that the therapy had significant antitumor effects against both primary and secondary tumors, improving the mouse survival rate from 0% to 50%. None of the re-challenged survivor mice developed tumors, and they had higher percentages of memory T cells versus control, suggesting the induction of long-term antitumor immune memory. The authors concluded that NBTXR3 in combination with radioimmunotherapy significantly improved anti-PD-1 resistant lung tumor control in mice by promoting antitumor immune response.