Late-stage clinical biotechnology company Nanobiotix announced promising first results of a Phase I study of the nanoradioenhancer NBTXR3 for patients with locally advanced Esophageal Adenocarcinoma. First results showed that six of all 13 patients (nearly 50%)  in the trial experienced a biopsy-confirmed complete response, three patients (more than 20%) had a partial response, and two patients (15%) saw their cancer remain stable. Two patients (15%) did not respond to the therapy.
Mechanism of Action
This approach works by injecting the tumor with NBTXR3 (hafnium oxide-containing nanoparticles), believed to cause targeted destruction of cancer cells. The drug is activated by radiation and results in nine times the energy being deposited into the tumor cells compared to radiation alone. Studies have shown that this induces significant tumor cell death without increasing damage to surrounding healthy tissue.

Treatment Plan
In this study, the nanoradioenhancer NBTXR3 was injected into the patients’ tumors. After two weeks, patients received radiation therapy five days a week for six weeks, along with chemotherapy. The announcement indicated that the treatment was well-tolerated.
Implications for Immuno-Oncology
Early clinical data suggest that radiotherapy-activated NBTXR3 may make cancer cells more visible to the immune system and prime the body’s immune response. Nanobiotix believes this may happen in several ways. One mechanism involves the release of damage-associated molecular patterns that are recognized by immune cells as a sign of cellular stress or injury. This may trigger an immune response against both the primary tumor and metastatic cells due to immunogenic cell death, a type of cell death that leads to activation of the immune system. Additionally, NBTXR3 has been shown to increase the expression of cell-surface proteins that enhance the presentation of tumor antigens to immune cells, possibly leading to improved recognition and destruction of cancer cells.
Next Steps

Underway at MD Anderson in Houston, Texas, investigators are recruiting an additional 17 patients to participate in further study of this novel approach.